Prevalence and associated clinical factors for overweight and obesity in young first-episode and drug-naïve Chinese patients with major depressive disorder.
Frontiers in psychiatry
Background:Obesity and overweight are common in young patients with major depressive disorder (MDD). However, the prevalence and associated clinical factors of obesity/overweight in young first-episode and drug-naïve (FEDN) MDD patients are rarely reported in China. Methods:A cross-sectional study of 917 young patients (aged 18-35 years) with FEDN MDD was performed. Demographic and clinical data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) positive subscale, respectively. Results:Among the young MDD patients, the prevalence of obesity and overweight was 4.14 and 52.89%, respectively. Compared to normal-weight patients, overweight patients were older, had a greater age of onset, and had higher TSH and TG levels. Male MDD patients had a higher risk of obesity than female patients. Compared to obese patients, normal-weight and overweight patients had significantly lower HAMD scores, TC levels, and rates of TSH abnormalities. Logistic regression analysis showed that age, age of onset, and sex were independently associated with obesity, and TSH was independently associated with both obesity and overweight, in young MDD patients. Conclusion:Our findings suggest a high prevalence of overweight and obesity in young FEDN MDD patients. Several demographic and clinical variables are independently associated with overweight/obesity in these young MDD patients.
10.3389/fpsyt.2023.1278566
Sex differences in the association of body mass index with symptoms and cognitive deficits in Chinese patients with chronic schizophrenia.
Translational psychiatry
Accumulating studies have revealed gender differences in many aspects of schizophrenia (SZ), including obesity and cognitive function. The relationship between obesity and cognitive impairment in SZ has been studied before; however, the results are inconsistent. This study was designed to examine the sex differences in the relationship between body mass index (BMI) and cognitive deficits in Chinese patients with chronic SZ, which have not been investigated yet. 176 chronic patients with SZ (male/female = 108/68) and 200 controls (male/female = 120/80) were enrolled to compare the sex differences in cognitive functions measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), BMI, and their associations. The clinical symptoms were evaluated using the positive and negative syndrome scales (PANSS). Our results showed that male patients had lower BMI and more negative symptoms but fewer positive symptoms than female patients (all p < 0.05). However, there was no significant sex difference in RBANS scores. In male patients, BMI was correlated with age of onset, PANSS general psychopathology, total score, negative symptom, together with RBANS language, visuospatial/construction, and attention. Further regression analysis showed that in male patients, BMI was significantly associated with RBANS language, PANSS general psychopathology, PANSS total score, and age of onset, with adjusted R = 0.22. These findings revealed significant sex differences in BMI, cognitive dysfunctions and their association in SZ. Nonetheless, these results should only be considered as preliminary because of the cross-sectional design, which will deserve further replication in first-episode patients using a prospective longitudinal design.
10.1038/s41398-020-0717-x
The prevalence of metabolic syndrome in patients with bipolar disorder.
Garcia-Portilla Maria P,Saiz Pilar A,Benabarre Antonio,Sierra Pilar,Perez Josefina,Rodriguez Alfonso,Livianos Lorenzo,Torres Pedro,Bobes Julio
Journal of affective disorders
BACKGROUND:Previous studies on the prevalence of metabolic syndrome (MetS) in patients with bipolar disorder have reported rates 11% and 79% higher than in their respective general populations. This study evaluates the prevalence of MetS in a group of 194 Spanish patients with bipolar disorder. METHODS:Naturalistic, multicentre, cross-sectional study. Patients were evaluated for presence of MetS according to modified NCEP ATP III criteria. RESULTS:Mean age was 46.6 (SD 13.9); 49.2% were male. Forty-six percent were in remission. Patients were receiving 2.9 (SD 1.3) drugs. Overall prevalence of MetS was 22.4%. Fifty-four percent met the criterion for abdominal obesity, 36.1% for hypertriglyceridemia, 38.2% for low HDL cholesterol, 20.9% for hypertension, and 12.2% for high fasting glucose. The multivariate analysis for MetS retained only the BMI variable in the model. LIMITATIONS:Cross-sectional study design. CONCLUSIONS:The prevalence of MetS in patients with bipolar disorder is 58% higher than that reported for the general Spanish population. MetS is associated with BMI. Clinicians should be aware of this issue and appropriately monitor patients with bipolar disorder for MetS as part of the standard of care for these patients.
10.1016/j.jad.2007.06.002
Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity.
Obesity (Silver Spring, Md.)
A growing number of youth suffer from obesity and in particular severe obesity for which intensive lifestyle intervention does not adequately reduce excess adiposity. A treatment gap exists wherein effective treatment options for an adolescent with severe obesity include intensive lifestyle modification or metabolic and bariatric surgery while the application of obesity pharmacotherapy remains largely underutilized. These youth often present with numerous obesity-related comorbid diseases, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, musculoskeletal problems, and psychosocial issues such as depression, anxiety, and social stigmatization. Current pediatric obesity treatment algorithms for pediatric primary care providers focus primarily on intensive lifestyle intervention with escalation of treatment intensity through four stages of intervention. Although a recent surge in the number of Food and Drug Administration-approved medications for obesity treatment has emerged in adults, pharmacotherapy options for youth remain limited. Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population, discussed here are the efficacy, safety, and clinical application of obesity pharmacotherapy in youth with obesity based on current literature. Legal ramifications, informed consent regulations, and appropriate off-label use of these medications in pediatrics are included, focusing on prescribing practices and prescriber limits.
10.1002/oby.22385
Contextual cues as modifiers of cTBS effects on indulgent eating.
Safati Adrian B,Hall Peter A
Brain stimulation
BACKGROUND:Prior studies have found that continuous theta burst stimulation (cTBS) targeting the left dlPFC results in reliable increases in consumption of calorie-dense food items. However, it is not known to what extent such effects are modified by cues in the immediate eating environment. Tempting environments (i.e., those saturated with appetitive eating cues) may lead to more reliance on cognitive control networks involving the dlPFC, thereby enhancing cTBS effects on indulgent eating. OBJECTIVE/HYPOTHESIS:The objective was to examine the extent to which cTBS effects on indulgent eating would be modified by contextual cues. It was hypothesized that cTBS effects would be stronger in the presence of facilitating cues. METHODS:Using a single-blinded between-subjects factorial design, 107 TMS-naïve adults were randomly assigned to one of four conditions: 1) active cTBS + facilitating cues, 2) sham cTBS + facilitating cues, 3) active cTBS + inhibiting cues, 4) sham cTBS + inhibiting cues. Following stimulation participants completed a flanker paradigm and a taste test during which quantity consumed was assessed surreptitiously. RESULTS:Findings revealed a significant interaction between stimulation and cue type (F(1,102) = 6.235, p = .014), such that cTBS resulted in increased food consumption (compared to sham) in the presence of the facilitating cue but not in the presence of the inhibiting cue. Moderated mediational analyses showed selective mediation of cTBS effects on consumption through cTBS attenuation of flanker interference scores. CONCLUSIONS:The effects of cTBS on indulgent eating are strengthened in the presence of facilitating cues. Methodologically speaking, facilitating cues may be a functional prerequisite for exploring cTBS effects on eating in the laboratory. Substantively, the findings also suggest that facilitating cues in the eating environment may amplify counter-intentional food indulgence in everyday life via cognitive control failure.
10.1016/j.brs.2019.05.003
High prevalence of metabolic diseases, liver steatosis and fibrosis among Chinese psychiatric patients.
BMC psychiatry
BACKGROUND:We aimed to investigate the differences of metabolic disorders between the general population and psychiatric patients, with an emphasis on the prevalence and influencing factors of liver fibrosis in psychiatric patients. METHODS:A total of 734 psychiatric patients and 734 general population matched for age, sex, and BMI were enrolled from Shanghai, China. All participants underwent blood pressure, glucose, lipid profile measurements, and anthropometric parameters including body weight, height and waist circumference. FibroScan examinations were also performed on psychiatric patients. Liver steatosis and fibrosis were diagnosed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by professional staff. RESULTS:Compared with the general population, psychiatric patients revealed significantly higher burden of metabolic disorders. The overall prevalence of liver steatosis (CAP ≥ 233 dB/m) and fibrosis (LSM ≥ 7.0 kPa) was 48.7% and 15.5% in psychiatric patients. Psychiatric patients with liver steatosis or fibrosis showed worse metabolic profile. Meanwhile, the prevalence of liver fibrosis was also significantly higher in patients with overweight, central obesity, diabetes, hypertension, metabolic syndrome, and liver steatosis. In logistic regression analyses, age, BMI and visceral adiposity index were independent risk factors for liver fibrosis in psychiatric patients. Additionally, antipsychotic medication was suggested to be associated with an increased risk of liver fibrosis in psychiatric patients with liver steatosis. CONCLUSIONS:Prevalence of liver steatosis and fibrosis is high in Chinese psychiatric patients. Those with antipsychotic polypharmacy and obesity are at high risk, and may benefit from early liver assessment in preventing fibrosis progression.
10.1186/s12888-023-04684-1
Elevated risk of liver steatosis in first-episode psychosis patients: Results from a 3-year prospective study.
Schizophrenia research
BACKGROUND:Cardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment. We aimed to assess the incidence of NAFLD and metabolic disturbances during the first 3 years of antipsychotic treatment in patients with first episode of psychosis (FEP), and compare it with the incidence in a control group. METHODS:Data were obtained from patients with psychosis (n = 160) and healthy controls (n = 66) included in the Cantabria's clinical and research program on FEP (PAFIP) from 2012 to 2018. Fatty Liver Index (FLI) was used to estimate the amount of fat in the liver. FLI has been validated for the diagnosis of NAFLD against different standards such as liver ultrasound and biopsy. FLI and metabolic parameters were registered at baseline, 3 months and then yearly for 3 years. RESULTS:At the end of the follow-up (3-years), 21.9 % of patients with psychosis developed a FLI ≥ 60, suggestive of liver steatosis, compared to only a 3 % of subjects within the control group (X = 12.120; p < 0.001). In the FEP patients group, developing a FLI ≥ 60 was statistically associated with significant increments in metabolic parameters, and with Metabolic Syndrome (MetS) (X = 16.151; p < 0.001) and high blood pressure (X = 10.654; p = 0.001). CONCLUSIONS:Having a first episode of non-affective psychosis was significantly associated with developing liver steatosis (FLI ≥ 60) in the first three years after initiating antipsychotic treatment. The results highlight the importance of early screening the emergence of NAFLD in schizophrenia patients.
10.1016/j.schres.2022.06.001
The Role of ElastPQ in Assessing Liver Stiffness for Non-Alcoholic Fatty Liver Disease in Patients Treated with Atypical Antipsychotic Drugs.
Neuropsychiatric disease and treatment
Objective:To evaluate the role of elastography point quantification (ElastPQ) for the quantitative assessment of stiffness in the fatty liver disease in mental disorder patients and to provide a noninvasive detection method for non-alcoholic fatty liver (NAFLD) caused by atypical antipsychotics drugs (AAPDs). Methods:A total number of 168 mental disorder patients treated with AAPDs and 58 healthy volunteers were enrolled in this study. All the subjects underwent ultrasound and ElastPQ tests. The basic data of the patients were analyzed. Results:BMI, liver function, and the value of ElastPQ were considerably higher in the patient group than that in the healthy volunteers. The values of liver stiffness obtained by ElastPQ were increased gradually from 3.48(3.14-3.81) kPa in the normal liver to 8.15(6.44-9.88) in the severe fatty liver. The receiver operating characteristic (ROC) for the diagnosis of fatty liver with ElastPQ were 0.85, 0.79, 0.80, and 0.87 for the diagnosis of normal, mild, moderate, and severe steatosis, respectively, with a sensitive/specificity of 79%/76.4%, 85.7%/78.3%, 86.2%/73%, and 81.3%/82.1%, correspondingly. Moreover, ElastPQ in the olanzapine group was higher than those in the risperidone and aripiprazole groups (5.11(3.83-5.61) kPa vs 4.35(3.63-4.98) kPa, P < 0.05; 5.11(3.83-5.61) kPa vs 4.79(4.18-5.24) kPa, P < 0.05). After one-year treatment, the value of ElastPQ was 4.43(3.85-5.22) kPa, but it was 5.81(5.09-7.33) kPa in patients treated for more than three years. This value increased with treatment prolongation (P < 0.05). Conclusion:ElastPQ is a real-time, quantitative method for assessing the stiffness of NAFLD. The liver stiffness value could be varied in the different stages of fatty liver. Olanzapine has a considerable influence on liver stiffness. The long-term use of AAPDs can increase the stiffness value of fatty liver.
10.2147/NDT.S409210
Prevalence and Influence Factors for Non-Alcoholic Fatty Liver Disease in Long-Term Hospitalized Patients with Schizophrenia: A Cross-Sectional Retrospective Study.
Neuropsychiatric disease and treatment
Purpose:Long-term hospitalized patients with schizophrenia (SCZ) are vulnerable to physical illness, leading to impaired life expectancy and treatment outcomes. There are few studies on the influence of non-alcoholic fatty liver disease (NAFLD) in long-term hospitalized patients. This study aimed to investigate the prevalence of and influence factors for NAFLD in hospitalized patients with SCZ. Patients and Methods:This cross-sectional retrospective study included 310 patients who had experienced long-term hospitalization for SCZ. NAFLD was diagnosed based on the results of abdominal ultrasonography. The -test, Mann-Whitney -test, correlation analysis, and logistic regression analysis were used to determine the influence factors for NAFLD. Results:Among the 310 patients who had experienced long-term hospitalization for SCZ, the prevalence of NAFLD was 54.84%. Antipsychotic polypharmacy (APP), body mass index (BMI), hypertension, diabetes, total cholesterol (TC), apolipoprotein B (ApoB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), uric acid, blood glucose, gamma-glutamyl transpeptidase (GGT), high-density lipoprotein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio significantly differed between the NAFLD and non-NAFLD groups (all <0.05). Hypertension, diabetes, APP, BMI, TG, TC, AST, ApoB, ALT, and GGT were positively correlated with NAFLD (all <0.05). The results of the logistic regression analysis indicated that APP, diabetes, BMI, ALT, and ApoB were the influence factors for NAFLD in patients with SCZ. Conclusion:Our results suggest a high prevalence of NAFLD among patients hospitalized long-term due to severe SCZ symptoms. Moreover, a history of diabetes, APP, overweight/obese status, and increased levels of ALT and ApoB were identified as negative factors for NAFLD in these patients. These findings may provide a theoretical basis for the prevention and treatment of NAFLD in patients with SCZ and contribute to the development of novel targeted treatments.
10.2147/NDT.S398385
Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study.
Morlán-Coarasa María José,Arias-Loste María Teresa,Ortiz-García de la Foz Víctor,Martínez-García Obdulia,Alonso-Martín Carmen,Crespo Javier,Romero-Gómez Manuel,Fábrega Emilio,Crespo-Facorro Benedicto
Psychopharmacology
RATIONALE:Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment. OBJECTIVES:Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients. RESULTS:A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (N = 83), risperidone (N = 12), quetiapine (N = 46), and ziprasidone (N = 50). At intake, 180 patients were antipsychotic naïve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score ≥60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score ≥60 and only 16.6 % who had a FLI score <30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score ≥60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score ≥ 60, 91.7 %; FLI < 60, 55.9 %; p < 0.001), increased triglyceride levels (FLI score ≥ 60, 54.2 %; FLI < 60, 5.6 %; p < 0.001), decreased HDL levels (FLI score ≥ 60, 41.7 %; FLI < 60, 17.5 %; p = 0.001), hypertension (FLI score ≥ 60, 19.5 %; FLI < 60, 4.5 %; p = 0.002), and waist circumference increase (steatosis 68.8 %; FLI < 60, 14.0 %; p < 0.001). CONCLUSIONS:Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.
10.1007/s00213-016-4422-7
Cannabis consumption and non-alcoholic fatty liver disease. A three years longitudinal study in first episode non-affective psychosis patients.
Vázquez-Bourgon Javier,Ortiz-García de la Foz Víctor,Suarez-Pereira Irene,Iruzubieta Paula,Arias-Loste María Teresa,Setién-Suero Esther,Ayesa-Arriola Rosa,Gómez-Revuelta Marcos,Crespo Javier,Crespo Facorro Benedicto
Progress in neuro-psychopharmacology & biological psychiatry
INTRODUCTION:Increased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis. MATERIAL AND METHODS:A total of 390 patients were evaluated at baseline and after 3 years of initiating the antipsychotic treatment. Anthropometric measurements and liver, lipid, and glycemic parameters were obtained at both time points. All but 6.7% of patients were drug-naïve at entry, and they self-reported their cannabis use at both time points. Liver steatosis and fibrosis were evaluated through validated clinical scores (Fatty Liver Index [FLI], Fibrosis-4 [FIB-4], and NAFLD). RESULTS:At 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F = 13.874; p < .001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X = 7.97, p = .019). Longitudinally, patients maintaining cannabis consumption after 3 years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p = .022) and never-users (p = .016). No differences were seen in fibrosis scores associated with cannabis. CONCLUSIONS:Cannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain.
10.1016/j.pnpbp.2019.109677
Non-alcoholic fatty liver disease in a sample of individuals with bipolar disorders: results from the FACE-BD cohort.
Godin Ophelia,Leboyer Marion,Belzeaux Raoul,Bellivier Frank,Loftus Joséphine,Courtet Philippe,Dubertret Caroline,Gard Sebastien,Henry Chantal,Llorca Pierre-Michel,Schwan Raymund,Passerieux Christine,Polosan Mircea,Samalin Ludovic,Olié Emilie,Etain Bruno,
Acta psychiatrica Scandinavica
OBJECTIVE:Non-Alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease in Western populations. While obesity and metabolic abnormalities are highly frequent in bipolar disorders (BD), no studies have been performed to estimate the prevalence of NALFD in individuals with BD. The aim of our study is to estimate the prevalence of NAFLD and to identify the potential associated risk factors in a large sample of BD individuals. METHODS:Between 2009 and 2019, 1969 BD individuals from the FACE-BD cohort were included. Individuals with liver diseases, Hepatitis B or C, and current alcohol use disorders were excluded from the analyses. A blood sample was drawn from participants. Screening of NAFLD was determined using fatty liver index (FLI). Individuals with FLI> 60 were considered as having NAFLD. RESULTS:The prevalence of NAFDL in this sample was estimated at 28.4%. NAFLD was observed in 40% of men and 21% of women. NAFLD was independently associated with older age, male gender, sleep disturbances, and current use of atypical antipsychotics or anxiolytics. As expected, the prevalence of NALFD was also higher in individuals with overweight and in those with metabolic syndrome. CONCLUSIONS:This study reinforces the view that individuals with BD are highly vulnerable to metabolic and cardiovascular diseases. The prevalence of NAFLD in individuals with BD was two times higher than the prevalence reported in the general population. The regular screening of the MetS in individuals with BD should be therefore complemented by the additional screening of NAFLD among these vulnerable individuals.
10.1111/acps.13239
Haloperidol, a sigma receptor 1 antagonist, promotes ferroptosis in hepatocellular carcinoma cells.
Biochemical and biophysical research communications
Ferroptosis is a novel form of cell death, which is characterized by accumulation of reactive oxygen species (ROS). Sigma 1 receptor (S1R) has been suggested to function in oxidative stress metabolism. Both erastin and sorafenib significantly induced S1R protein expression. Haloperidol strongly promoted erastin- and sorafenib-induced cell death, which was blocked by ferrostatin-1 but not ZVAD-FMK or necrosulfonamide. During ferroptosis, haloperidol substantially increased the cellular levels of Fe, GSH and lipid peroxidation. Furthermore, several ferroptosis-related protein targets were up-regulated in the absence of haloperidol. Thus, Our study identified an association between haloperidol and ferroptosis for the first time. Our analyses of a combination of drugs may provide a novel strategy of hepatocellular carcinoma (HCC) therapy.
10.1016/j.bbrc.2017.07.136
Haloperidol Prevents Oxytosis/Ferroptosis by Targeting Lysosomal Ferrous Ions in a Manner Independent of Dopamine D2 and Sigma-1 Receptors.
ACS chemical neuroscience
Haloperidol is a widely used antipsychotic agent that exerts antipsychotic effects through a strong antagonism of dopamine D2 receptors. In addition, haloperidol is classified as a sigma-1 receptor (S1R) antagonist that prevents endogenous oxidative stress in cultured cells. However, pharmacological activities of haloperidol against oxidative stress remain unclear. Oxytosis/ferroptosis are iron-dependent nonapoptotic oxidative cell deaths that are regarded as two names for the same cell death pathway and the potential physiological relevance of oxytosis/ferroptosis in multiple diseases is suggested. In the present study, the effects of haloperidol on oxytosis/ferroptosis were investigated in S1R-knockdown mouse hippocampal HT22 cells. The results indicate that haloperidol is a strong inhibitor of oxytosis/ferroptosis independent of S1R. Imaging of HT22 cells with a newly developed fluorescent probe showed that haloperidol was localized to late endosomes and lysosomes and reduced the accumulation of lysosomal ferrous ions, resulting in reduced production of intracellular reactive oxygen species and inhibition of cell death. These results indicate that haloperidol is useful not only as an antipsychotic agent but also as a neuroprotective agent against endogenous oxidative stress via distinct mechanisms. Furthermore, lysosome-targeting ferroptosis inhibitors could be useful for the treatment of various diseases, including cancers, ischemia-reperfusion injury, and neurodegenerative disorders, which have been associated with ferroptosis.
10.1021/acschemneuro.2c00398
Discovery and optimization of olanzapine derivatives as new ferroptosis inhibitors.
Bioorganic chemistry
Ferroptosis is a new type of cell death associated with many human diseases. It is a new strategy to discover ferroptosis inhibitors for the treatment of ferroptosis-related diseases. Here the FDA-approved drug library containing 1160 molecules was screened for ferroptosis inhibitors in RSL3-induced HT22 mouse hippocampal neuronal cells. As a result, olanzapine showed potent ferroptosis inhibitory activity (EC = 1.18 μM). Structural optimization and the structure-activity relationships (SARs) analysis led to the synthesis of 41 new derivatives (4-44) and one known compound 45. Comparing with olanzapine, its derivative 36 showed nearly sixteen-folds improved ferroptosis inhibition and low cytotoxicity (EC = 0.074 μM, CC = 18.8 μM). Further mechanistic studies revealed that compound 36 specifically inhibited ferroptosis by its antioxidative ability. This work demonstrates that olanzapine protected RSL3-induced ferroptosis in HT22 cell, and its derivative 36 having nanomolar ferroptosis inhibitory activity merit to be developed for drugs against ferroptosis-related neurological diseases.
10.1016/j.bioorg.2023.106393
Effects of oxytocin and genetic variants on brain and behaviour: Implications for treatment in schizophrenia.
Bartholomeusz Cali F,Ganella Eleni P,Labuschagne Izelle,Bousman Chad,Pantelis Christos
Schizophrenia research
Impairments in social cognition and poor social functioning are core features of schizophrenia-spectrum disorders. In recent years, there has been a move towards developing new treatment strategies that specifically target social cognitive and social behavioural deficits. Oxytocin (OXT) is one such strategy that has gained increasing attention. There is a strong rationale for studying OXT in psychosis, from both an evolutionary perspective and neurodevelopmental-cognitive model of schizophrenia. Thus, the aim of this review was to critique and examine the observational and clinical oxytocin trial literature in schizophrenia-spectrum disorders. A handful of clinical trials suggest that OXT treatment may be beneficial for remediating social cognitive impairments, psychiatric symptoms, and improving social outcomes. However, inconsistencies exist in this literature, which may be explained by individual differences in the underlying neural response to OXT treatment and/or variation in the oxytocin and oxytocin receptor genes. Therefore, we additionally reviewed the evidence for structural and functional neural intermediate phenotypes in humans that link genetic variants to social behaviour/thinking, and discuss the implications of such interactions in the context of dysfunctional brain networks in schizophrenia. Factors that pose challenges for future OXT clinical research include the impact of age, sex, and ancestry, task-specific effects, bioavailability and pharmacokinetics, as well as neurotransmitter and drug interactions. While initial findings from OXT single dose/clinical trial studies are promising, more interdisciplinary research in both healthy and psychiatric populations is needed before determining whether OXT is a viable treatment option/adjunct for addressing poor illness outcomes in psychotic disorders.
10.1016/j.schres.2015.06.007
Higher serum uric acid to HDL-cholesterol ratio is associated with onset of non-alcoholic fatty liver disease in a non-obese Chinese population with normal blood lipid levels.
BMC gastroenterology
BACKGROUND:Recent studies have demonstrated the presence of associations between metabolic syndrome and the onset of nonalcoholic fatty liver disease (NAFLD). Metabolic syndrome, in turn, has been found to be linked to high serum uric acid to HDL-cholesterol ratios (UHR). However, the relationship between UHR values and the occurrence of NAFLD in non-obese individuals remains unknown. The present study aimed to examine the possible correlation between UHR values and NAFLD onset among a non-obese Chinese population without dyslipidemia, as well as comparing the predictive value of UHR versus other NAFLD onset predictors. METHODS:A total of 9837 non-obese patients, with normal blood lipid levels, were included in a 5-year retrospective cohort study, and the onset of NAFLD in these patients was diagnosed by liver ultrasound. RESULTS:Out of the 9837 patients, 855 were diagnosed with NAFLD during the 5-year follow-up period, for an overall total prevalence of 8.7% at the end of the study period. Across quintiles 1, 2, 3, 4 and 5 of UHR (respectively, ratios of ≤ 120.88, 120.89-154.01, 154.02-189.91, 189.92-240.46, and ≥ 240.47), the prevalence of NAFLD among the patients increased from 2.4%, 5%, 7.9%, 10.3%, and 17.8%, respectively. After adjustments for age, gender, liver and kidney functional markers, as well as metabolic indicators, multivariate Cox proportional hazard regression analysis demonstrated that the hazard ratio (HR) was the highest in quintile 5, at 1.76 (1.12-2.75), and the lowest in quintile 1. The area under the curve (AUC) for UHR (0.690) was higher than that for serum uric acid (UA, 0.666) and HDL-C (0.636), suggesting the predictive ability of UHR for NAFLD onset was better than either alone. This finding was further supported by the presence of an independent association between UHR and NAFLD, even within the normal range of UA and HDL-C; the HR (95% confidence interval, CI) for NAFLD was 1.002 (1.000-1.004). Compared with other significant predictors, AUC for UHR (0.67) was similar to that of low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C, 0.68), non-high-density lipoprotein cholesterol (NHDL-C)/HDL-C (0.68) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratios (0.7), and was higher than that of LDL-C (0.63), remnant cholesterol (RC,0.59), and albumin (ALB)/alkaline phosphatase (ALP) ratio (0.61). The sensitivity of UHR (71%) was the highest among all indicators. In the subgroup with ALT < 40U/L, the AUC for UHR was 0.70, which was the highest among all predictors; among ALT > 40U/L, UHR was able to predict the occurrence of NAFLD (AUC = 0.61, p = 0.007), which was not the case for RC (P = 0.441), ALB/ALP (P = 0.419), and ALT/AST (P = 0.159). CONCLUSIONS:UHR serve as an inexpensive and reliable predictor of NAFLD onset in non-obese Chinese people with normal blood lipid levels, allowing for identification of individuals at high risk for NAFLD.
10.1186/s12876-022-02263-4
The association between metabolic risk factors, nonalcoholic fatty liver disease, and the incidence of liver cancer: a nationwide population-based cohort study.
Hepatology international
BACKGROUND AND AIMS:Liver cancer is a detrimental complication in patients with chronic viral hepatitis and alcoholic or nonalcoholic fatty liver disease (NAFLD). However, metabolic risk factors underlying NAFLD usually cause substantial differences in their clinical outcomes. Recently, several studies have used a novel definition of metabolic dysfunction-associated fatty liver disease (MAFLD) to reassess patients with NAFLD and pointed out the importance of metabolic risk factors. Since patients with NAFLD, MAFLD, or metabolic syndrome (MetS) have different burden of metabolic risk factors, it is crucial to decipher the risk of developing hepatic complications in these populations. METHODS:Through a longitudinal nationwide cohort study, the risk of liver cancer was investigated in patients with MetS alone, NAFLD alone, overlap NAFLD/MAFLD, and coexisting MetS and NAFLD. The general characteristics, comorbidities, and incidence of liver cancer were also compared. RESULTS:Intriguingly, patients diagnosed with MetS alone did not have a significant risk of developing HCC compared to control individuals, while patients with NAFLD alone, NAFLD/MAFLD, and coexisting NAFLD and MetS exhibited 6.08-, 5.81-, and 15.33-fold risks of developing HCC, respectively. Apart from metabolic risk factors, renal function status and liver cirrhosis were the independent risk factors for the development of HCC among these groups. CONCLUSION:Our data emphasize that metabolic dysfunction has a significant impact on hepatocarcinogenesis in patients with NAFLD. Moreover, coexisting multiple metabolic risk factors would dampen the risk of developing HCC in patients with NAFLD. Closely tracing HCC formation through laboratory examination or imaging is crucial in these patients.
10.1007/s12072-021-10281-9
Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring.
Buffington Shelly A,Di Prisco Gonzalo Viana,Auchtung Thomas A,Ajami Nadim J,Petrosino Joseph F,Costa-Mattioli Mauro
Cell
Maternal obesity during pregnancy has been associated with increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Here, we report that maternal high-fat diet (MHFD) induces a shift in microbial ecology that negatively impacts offspring social behavior. Social deficits and gut microbiota dysbiosis in MHFD offspring are prevented by co-housing with offspring of mothers on a regular diet (MRD) and transferable to germ-free mice. In addition, social interaction induces synaptic potentiation (LTP) in the ventral tegmental area (VTA) of MRD, but not MHFD offspring. Moreover, MHFD offspring had fewer oxytocin immunoreactive neurons in the hypothalamus. Using metagenomics and precision microbiota reconstitution, we identified a single commensal strain that corrects oxytocin levels, LTP, and social deficits in MHFD offspring. Our findings causally link maternal diet, gut microbial imbalance, VTA plasticity, and behavior and suggest that probiotic treatment may relieve specific behavioral abnormalities associated with neurodevelopmental disorders. VIDEO ABSTRACT.
10.1016/j.cell.2016.06.001
Predictors of non-alcoholic fatty liver disease in children.
Pediatric research
OBJECTIVE:Abdominal obesity is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). Early identification and intervention may reduce the risk. We aim to improve pediatric NAFLD screening by comparing discriminative performance of six abdominal obesity indicators. METHODS:We measured anthropometric indicators (waist circumference [WC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR]), body composition indicators (trunk fat index [TFI], visceral fat area [VFA]), and endocrine indicator (visceral adiposity index [VAI]) among 1350 Chinese children aged 6-8 years. Using Spearman correlation, receiver operating characteristic (ROC) curves, and Logistic regression, we validated their ability to predict NAFLD. RESULTS:All six indicators can predict NAFLD robustly, with area under the curve (AUC) values ranged from 0.69 to 0.96. TFI, WC, and VFA rank in the top three for the discriminative performance. TFI was the best predictor with AUC values of 0.94 (0.92-0.97) and 0.96 (0.92-0.99), corresponding to cut-off values of 1.83 and 2.31 kg/m for boys and girls, respectively. Boys with higher TFI (aOR = 13.8), VFA (aOR = 11.1), WHtR (aOR = 3.1), or VAI (aOR = 2.8), and girls with higher TFI (aOR = 21.0) or VFA (aOR = 17.5), were more likely to have NAFLD. CONCLUSION:User-friendly body composition indicators like TFI can identify NAFLD and help prevent the progress of liver disease. TRIAL REGISTRATION:Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn/enIndex.aspx , No. ChiCTR2100044027); retrospectively registered on 6 March 2021. IMPACT:Abdominal obesity increases the risk of pediatric non-alcoholic fatty liver disease (NAFLD). This study compared the discriminative performance of multiple abdominal obesity indicators measured by different methods in terms of accuracy and fastidious cut-off values through a population-based child cohort. Our results provided solid evidence of abdominal obesity indicators as an optimal screening tool for pediatric NAFLD, with area under the curve (AUC) values ranged from 0.69 to 0.96. User-friendly body composition indicators like TFI show a greater application potential in helping physicians perform easy, reliable, and interpretable weight management to prevent the progress of liver damage.
10.1038/s41390-021-01754-6
Non-alcoholic fatty liver disease and obesity: not all about body mass index.
Pagadala Mangesh R,McCullough Arthur J
The American journal of gastroenterology
Patients with nonalcoholic fatty liver (NAFLD) are typically obese and confounded by the metabolic syndrome. The body mass index (BMI) is often used as a surrogate marker of obesity defined as a BMI >30 λkg/m(2). However, it is now apparent that it is the distribution of body fat (not total fat) that is associated with NAFLD. Many patients (as many as 25%) with NAFLD are nonobese. This is particularly true in Asians who have a significantly increased risk of cardiovascular disease and diabetes even among those with a normal BMI. It is important for clinicians to be aware that these "metabolically obese" NAFLD patients should be monitored for the metabolic syndrome and its associated adverse outcomes irrespective of their BMI.
10.1038/ajg.2012.320
New trends on obesity and NAFLD in Asia.
Fan Jian-Gao,Kim Seung-Up,Wong Vincent Wai-Sun
Journal of hepatology
Traditionally, obesity and its related diseases have been considered a problem in Western countries. However, in the past two decades, urbanisation in many Asian countries has led to a sedentary lifestyle and overnutrition, setting the stage for the epidemic of obesity. This article reviews the epidemiological trend of obesity in Asia, with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is around 25%, like many Western countries. While hepatocellular carcinoma and end-stage liver disease secondary to NAFLD remain uncommon, a rising trend has emerged. Around 8-19% of Asians with body mass indexes less than 25kg/m are also found to have NAFLD, a condition often described as "lean" or "non-obese" NAFLD. Although this condition is generally less severe than that in more obese patients, steatohepatitis and fibrotic disease are well recognized. Central adiposity, insulin resistance and weight gain are major risk factors, and genetic predisposition, such as the PNPLA3 polymorphism appears to be more important in the development of NAFLD in the non-obese population. Lifestyle modification remains the cornerstone of management for obesity and NAFLD, but few patients can achieve adequate weight reduction and even fewer can maintain the weight in the long run. While pharmacological agents have entered phase III development for steatohepatitis, Asian patients are under-represented in most drug trials. Future studies should define the optimal management of obesity and NAFLD in Asia.
10.1016/j.jhep.2017.06.003
The usefulness of obesity and lipid-related indices to predict the presence of Non-alcoholic fatty liver disease.
Sheng Guotai,Lu Song,Xie Qiyang,Peng Nan,Kuang Maobin,Zou Yang
Lipids in health and disease
BACKGROUND:Conicity index, body-shape index, lipid accumulation product (LAP), waist circumference (WC), triglyceride, triglyceride-glucose (TyG) index, hepatic steatosis index (HSI), waist-to-height ratio (WHtR), TyG index-related parameters (TyG-WHtR, TyG-BMI, TyG-WC), body mass index (BMI), visceral adiposity index, triglyceride to high-density lipoprotein cholesterol ratio and body roundness index have been reported as reliable markers of non-alcoholic fatty liver disease (NAFLD). However, there is debate about which of the above obesity and lipid-related indices has the best predictive performance for NAFLD risk. METHODS:This study included 6870 female and 7411 male subjects, and 15 obesity and lipid-related indices were measured and calculated. NAFLD was diagnosed by abdominal ultrasound. The area under the curve (AUC) of 15 obesity and lipid-related indices were calculated by receiver operating characteristic (ROC) analysis. RESULTS:Among the 15 obesity and lipid-related indices, the TyG index-related parameters had the strongest association with NAFLD. ROC analysis showed that except for ABSI, the other 14 parameters had high predictive value in identifying NAFLD, especially in female and young subjects. Most notably, TyG index-related parameters performed better than other parameters in predicting NAFLD in most populations. In the female population, the AUC of TyG-WC for predicting NAFLD was 0.9045, TyG-BMI was 0.9084, and TyG-WHtR was 0.9071. In the male population, the AUC of TyG-WC was 0.8356, TyG-BMI was 0.8428, and TyG-WHtR was 0.8372. In addition, BMI showed good NAFLD prediction performance in most subgroups (AUC>0.8). CONCLUSIONS:Our data suggest that TyG index-related parameters, LAP, HSI, BMI, and WC appear to be good predictors of NAFLD. Of these parameters, TyG index-related parameters showed the best predictive potential.
10.1186/s12944-021-01561-2
Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.
Milić Sandra,Lulić Davorka,Štimac Davor
World journal of gastroenterology
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.
10.3748/wjg.v20.i28.9330
Subthreshold Change in Glycated Hemoglobin and Body Mass Index After the Initiation of Second-Generation Antipsychotics Among Patients With Schizophrenia or Bipolar Disorder: A Nationwide Prospective Cohort Study in Japan.
The Journal of clinical psychiatry
The risk of diabetes development has been reported to differ among second-generation antipsychotics (SGAs). However, few studies have focused on the subthreshold change in glycated hemoglobin (HbA). Therefore, this study examined the subthreshold change in HbA and change in body mass index (BMI) 3 months after patients initiated one of 6 SGAs widely prescribed in Japan. This is a prospective cohort study of patients followed up based on the Japanese blood glucose monitoring guidelines for patients with schizophrenia. We collected eligible patients' demographic data, medication history, blood tests, and weight measurements both at baseline and 3 months after recruitment, between April 2013 and March 2015. In the 378 patients with schizophrenia, schizoaffective disorder, and bipolar disorder based on , we compared the subthreshold change in HbA and the change in BMI 3 months after antipsychotic initiation by using multivariate regression analysis. The subthreshold change in HbA 3 months after initiating blonanserin was significantly lower compared with olanzapine ( = -0.17, 95% CI = -0.31 to -0.04). In addition, the change in BMI 3 months after initiating blonanserin and aripiprazole was significantly lower compared with olanzapine ( = -0.93, 95% CI = -1.74 to -0.12; = -0.71, 95% CI = -1.30 to -0.12, respectively). This is the first study to clarify the differences in the subthreshold change in HbA among SGAs. Our results suggest that blonanserin is likely to be a favorable treatment for patients with high risk of diabetes. UMIN Clinical Trial Registry identifier: UMIN000009868.
10.4088/JCP.21m14099
Inverse association between negative symptoms and body mass index in chronic schizophrenia.
Mezquida G,Savulich G,Garcia-Rizo C,Garcia-Portilla M P,Toll A,Garcia-Alvarez L,Bobes J,Mané A,Bernardo M,Fernandez-Egea E
Schizophrenia research
BACKGROUND:We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS:62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS:Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS:We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels.
10.1016/j.schres.2017.04.002
Homocysteine level, body mass index and clinical correlates in Chinese Han patients with schizophrenia.
Huang Yuanyuan,Wu Kai,Li Hehua,Zhou Jing,Xiong Dongsheng,Huang Xia,Li Jiahui,Liu Ya,Pan Zhilin,Mitchell David T,Wu Fengchun,Zhang Xiang Yang
Scientific reports
Obesity is common comorbidity in patients with schizophrenia. Previous studies have reported that homocysteine (Hcy) is increased in schizophrenia. However, no study has reported the association between BMI and Hcy levels in schizophrenia. This cross-sectional naturalistic study aimed to evaluate the relationship between BMI, Hcy and clinical symptoms in Chinese Han patients with chronic schizophrenia. Clinical and anthropometric data as well as plasma Hcy level and glycolipid parameters were collected. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Our results showed that compared with the low BMI group, the high BMI group had a higher PANSS general psychopathology subscore, higher levels of blood glucose, total cholesterol and high-density lipoprotein (HDL) cholesterol (all p < 0.05). Hcy levels were negatively associated with BMI in patients (p < 0.001). Hcy level, the PANSS general psychopathology subscale, total cholesterol and education (all p < 0.05) were the influencing factors of high BMI. Our study suggest that Hcy level may be associated with BMI in patients with schizophrenia. Moreover, patients with high BMI show more severe clinical symptoms and higher glucose and lipid levels.
10.1038/s41598-020-72934-3
Body mass index and psychiatric disorders: a Mendelian randomization study.
Scientific reports
Obesity is a highly prevalent risk factor for cardiometabolic diseases. Observational studies suggest that obesity is associated with psychiatric traits, but causal inference from such studies has several limitations. We used two-sample Mendelian randomization methods (inverse variance weighting, weighted median and MR-Egger regression) to evaluate the association of body mass index (BMI) with three psychiatric traits using data from the Genetic Investigation of Anthropometric Traits and Psychiatric Genomics consortia. Causal odds ratio estimates per 1-standard deviation increment in BMI ranged from 0.88 (95% CI: 0.62; 1.25) to 1.23 (95% CI: 0.65; 2.31) for bipolar disorder; 0.93 (0.78; 1.11) to 1.41 (0.87; 2.27) for schizophrenia; and 1.15 (95% CI: 0.92; 1.44) to 1.40 (95% CI: 1.03; 1.90) for major depressive disorder. Analyses removing potentially influential SNPs suggested that the effect estimates for depression might be underestimated. Our findings do not support the notion that higher BMI increases risk of bipolar disorder and schizophrenia. Although the point estimates for depression were consistent in all sensitivity analyses, the overall statistical evidence was weak. However, the fact that SNP-depression associations were estimated in relatively small samples reduced power to detect causal effects. This should be re-addressed when SNP-depression associations from larger studies become available.
10.1038/srep32730
Correlations between Body Mass Index, Plasma High-Sensitivity C-Reactive Protein and Lipids in Patients with Schizophrenia.
Boozalis Ted,Devaraj Sridevi,Okusaga Olaoluwa O
The Psychiatric quarterly
High prevalence of obesity in individuals with schizophrenia, associated with metabolic syndrome, leads to high rate of premature deaths from cardiovascular disease (CVD) in this population. Body mass index (BMI) and C-reactive protein (CRP) are correlated in the general population but this relationship has not been fully elucidated in patients with schizophrenia. We aimed to evaluate the correlation between BMI and CRP while relating both variables to plasma lipids in patients with schizophrenia. BMI, fasting high sensitivity CRP (hs-CRP), cotinine, and lipids were measured in 106 patients with schizophrenia (diagnosis confirmed with MINI). Pearson's and partial correlations (adjusting for age, sex, race, education and cotinine) between BMI, hs-CRP and lipids were calculated. Based on BMI, the patients were divided into normal-weight vs. overweight/obese and t-tests and linear regression were done to compare hs-CRP and lipids in the 2 groups. BMI positively correlated with hs-CRP (r = 0.29, p = 0.004). BMI and hs-CRP negatively correlated with HDL in the total sample (r = -0.29, p = 0.004; r = -0.37, p < 0.001 respectively). Furthermore, hs-CRP negatively correlated with HDL in overweight/obese patients (r = -0.41, p = 0.003), but not in normal-weight patients. hs-CRP and triglycerides were higher (1.62 ± 0.09 mg/L vs. 0.56 ± 0.08 mg/L, p < 0.001; 121.77 ± 8.96 mg/dL vs. 91.23 ± 6.52 mg/dL, p = 0.008 respectively) and HDL lower (39.55 ± 1.48 mg/dL vs. 50.68 ± 2.24 mg/dL, p < 0.001) in overweight/obese patients. Being overweight/obese is associated with increased inflammation and dyslipidemia in patients with schizophrenia. Effective interventions to prevent weight gain in schizophrenia are urgently needed.
10.1007/s11126-018-9606-3
Gray matter reduction in bilateral insula mediating adverse psychiatric effects of body mass index in schizophrenia.
BMC psychiatry
BACKGROUND:Both schizophrenia (SZ) and overweight/obesity (OWB) have shown some structural alterations in similar brain regions. As higher body mass index (BMI) often contributes to worse psychiatric outcomes in SZ, this study was designed to examine the effects of OWB on gray matter volume (GMV) in patients with SZ. METHODS:Two hundred fifty subjects were included and stratified into four groups (n = 69, SZ patients with OWB, SZ-OWB; n = 74, SZ patients with normal weight, SZ-NW; n = 54, healthy controls with OWB, HC-OWB; and n = 53, HC with NW, HC-NW). All participants were scanned using high-resolution T1-weighted sequence. The whole-brain voxel-based morphometry was applied to examine the GMV alterations, and a 2 × 2 full factorial analysis of variance was performed to identify the main effects of diagnosis (SZ vs HC), BMI (NW vs OWB) factors, and their interactions. Further, the post hoc analysis was conducted to compare the pairwise differences in GMV alterations. RESULTS:The main effects of diagnosis were located in right hippocampus, bilateral insula, rectus, median cingulate/paracingulate gyri and thalamus (SZ < HC); while the main effects of BMI were displayed in right amygdala, left hippocampus, bilateral insula, left lingual gyrus, and right superior temporal gyrus (OWB < NW). There were no significant diagnosis-by-BMI interaction effects in the present study, but the results showed that both SZ and OWB were additively associated with lower GMV in bilateral insula. Moreover, mediation analyses revealed the indirect effect of BMI on negative symptom via GMV reduction in bilateral insula. CONCLUSION:This study further supports that higher BMI is associated with lower GMV, which may increase the risk of unfavourable disease courses in SZ.
10.1186/s12888-022-04285-4
Body Mass Index and risk for onset of mood and anxiety disorders in the general population: Results from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2).
BMC psychiatry
BACKGROUND:Examine the onset of a clinical diagnosis of mood (major depression, dysthymia and bipolar disorder)- and anxiety disorders (panic disorder, agoraphobia without panic disorder, social phobia, specific phobia and generalized anxiety disorder) by Body Mass Index levels at baseline in the general adult population over three years. METHODS:Data are from NEMESIS-2, a representative psychiatric cohort study in the Netherlands. A total of 5303 subjects aged 18-64 were interviewed with the CIDI (3.0 based on DSM-IV) in two waves, with an interval of three years. The first wave was performed from November 2007 to July 2009, the second wave from November 2010 to June 2012. RESULTS:Persons with obesity at baseline had a significantly increased risk of the onset of any mood -or anxiety disorder adjusting for covariates compared to persons with a normal Body Mass Index (OR = 1.71; 95% CI: 1.11-2.62). The odds ratio of the underweight category was non-significant. A dose-response effect of the continuous BMI scores on the onset of any mood or anxiety disorder was found (OR = 1.06; 95% CI: 1.02 = 1.10; p < 0.01). CONCLUSIONS:Obesity at baseline is a risk for the onset of mood -and anxiety disorders at three year follow up.
10.1186/s12888-022-04077-w
Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder.
BMC psychiatry
BACKGROUND:Many second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk. METHODS:Patients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013-February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions. RESULTS:Median follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG. CONCLUSIONS:In this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.
10.1186/s12888-022-03758-w
Machine learning-based predictive models and drug prediction for schizophrenia in multiple programmed cell death patterns.
Frontiers in molecular neuroscience
Background:Schizophrenia (SC) is one of the most common mental illnesses. However, the underlying genes that cause it and its effective treatments are unknown. Programmed cell death (PCD) is associated with many immune diseases and plays an important role in schizophrenia, which may be a diagnostic indicator of the disease. Methods:Two groups as training and validation groups were chosen for schizophrenia datasets from the Gene Expression Omnibus Database (GEO). Furthermore, the PCD-related genes of the 12 patterns were extracted from databases such as KEGG. Limma analysis was performed for differentially expressed genes (DEG) identification and functional enrichment analysis. Machine learning was employed to identify minimum absolute contractions and select operator (LASSO) regression to determine candidate immune-related center genes, construct protein-protein interaction networks (PPI), establish artificial neural networks (ANN), and validate with consensus clustering (CC) analysis, then Receiver operating characteristic curve (ROC curve) was drawn for diagnosis of schizophrenia. Immune cell infiltration was developed to investigate immune cell dysregulation in schizophrenia, and finally, related drugs with candidate genes were collected the Network analyst online platform. Results:In schizophrenia, 263 genes were crossed between DEG and PCD-related genes, and machine learning was used to select 42 candidate genes. Ten genes with the most significant differences were selected to establish a diagnostic prediction model by differential expression profiling. It was validated using artificial neural networks (ANN) and consensus clustering (CC), while ROC curves were plotted to assess diagnostic value. According to the findings, the predictive model had a high diagnostic value. Immune infiltration analysis revealed significant differences in Cytotoxic and NK cells in schizophrenia patients. Six candidate gene-related drugs were collected from the Network analyst online platform. Conclusion:Our study systematically discovered 10 candidate hub genes (, , , , , , , , , and ). A good diagnostic prediction model was obtained through comprehensive analysis in the training (AUC 0.91, CI 0.95-0.86) and validation group (AUC 0.94, CI 1.00-0.85). Furthermore, drugs that may be useful in the treatment of schizophrenia have been obtained (Valproic Acid, Epigallocatechin gallate).
10.3389/fnmol.2023.1123708
Serum hepcidin / ferroportin levels in bipolar disorder and schizophrenia.
Keleş Altun İlkay,Atagün Murat İlhan,Erdoğan Ali,Oymak Yenilmez Dicle,Yusifova Aygün,Şenat Almila,Erel Özcan
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
BACKGROUND:Despite several alternatives for cellular iron influx, the only mechanism for cellular iron efflux is ferroportin mediated active transport. In cases of ferroportin dysfunction, iron accumulates in the cell and causes ferroptosis. Hepcidin suppresses ferroportin levels and inflammatory activation increases hepcidin production. Mild inflammation in schizophrenia and bipolar disorder may alter hepcidin and ferroportin. METHODS:The study included a total of 137 patients aged 18-65 years, 57 diagnosed with schizophrenia and 80 with bipolar disorder, according to the DSM-IV diagnostic criteria, and a control group (HC) of 42 healthy individuals. Biochemical analyses, thyroid function tests, hemogram, serum iron level, iron-binding capacity, and ferritin levels were examined. Serum levels of hepcidin and ferroportin were measured with enzyme-linked immunosorbent assay (ELISA) method. RESULTS:A statistically significant difference was determined between the groups in terms of the serum ferroportin levels (F = 15.69, p < 0.001). Post-hoc analyses showed that the schizophrenia group had higher ferroportin levels than in the bipolar group (p < 0.001) and HCs (p < 0.001). Hepcidin levels did not differ between the groups. Chlorpromazine equivalent doses of antipsychotics correlated with ferroportin levels (p = 0.024). CONCLUSION:Ferroportin levels were increased in the schizophrenia group, although iron and hepcidin levels were within normal ranges. Antipsychotics may alter the mechanisms which control ferroportin levels. Further studies are needed to examine the relationships between antipsychotics and iron metabolism for determination of causal relationship.
10.1016/j.jtemb.2021.126843
The association between adolescent depression and dyslipidemia.
Journal of affective disorders
BACKGROUND:Children and adolescents with major depressive disorder (MDD) are at increased risk for premature cardiovascular disease (CVD). Whether adolescents with MDD manifest evidence of dyslipidemia, a key risk factor for CVD, is unknown. METHODS:Youth recruited through an ambulatory psychiatry clinic and the community, were categorized following diagnostic interview as MDD or as healthy controls [HC]. CVD risk factors including high density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride concentrations were collected. Depression severity was measured using the Center for Epidemiological Studies Depression Scale for Children. The associations of diagnostic group as well as depressive symptom severity with lipid concentrations were examined using multiple regression analyses. Models were adjusted for age, sex, and standardized Body Mass Index. RESULTS:Participants (n = 243) were 68 % female with a mean age of 15.04 ± 1.81 years. MDD and HC participants had comparable levels of dyslipidemia (MDD: 48 %, HC: 46 %, p > .7) and hypertriglyceridemia (MDD: 34 %, HC: 30 %, p > .7). Among depressed adolescents, greater depressive symptoms were associated with higher total cholesterol concentrations in unadjusted models only. Greater depressive symptoms were associated with higher HDL concentrations and a lower triglyceride-to-HDL ratio, after adjusting for covariates. LIMITATIONS:Cross-sectional design. CONCLUSIONS:Adolescents with clinically significant depressive symptoms manifested similar levels of dyslipidemia as healthy youth. Future studies examining the prospective trajectories of depressive symptoms and lipid concentrations are needed to determine the point at which dyslipidemia emerges in the course of MDD, and the mechanism of the association that imparts increased CVD risk for depressed youth.
10.1016/j.jad.2023.06.017
Obesity is associated with previous suicide attempts in bipolar disorder.
Gomes Fabiano A,Kauer-Sant'Anna Márcia,Magalhães Pedro V,Jacka Felice N,Dodd Seetal,Gama Clarissa S,Cunha Angelo,Berk Michael,Kapczinski Flávio
Acta neuropsychiatrica
UNLABELLED:Gomes FA, Kauer-Sant'Anna M, Magalhães PV, Jacka FN, Dodd S, Gama CS, Cunha Â, Berk M, Kapczinski F. Obesity is associated with previous suicide attempts in bipolar disorder. OBJECTIVE:There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder. METHODS:Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese. RESULTS:Over 30% of the sample was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06-3.69, p = 0.03) as likely to have a history of suicide attempt(s). CONCLUSION:Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients.
10.1111/j.1601-5215.2010.00452.x
Childhood obesity: increased risk for cardiometabolic disease and cancer in adulthood.
Weihrauch-Blüher Susann,Schwarz Peter,Klusmann Jan-Henning
Metabolism: clinical and experimental
Prevalence of childhood obesity has worldwide more than doubled since 1980. Underlying factors are complex and are far from completely understood. Strategies to prevent childhood obesity have mainly focused on behavioral intervention; and obesity therapy was mainly based on lifestyle modification to date. However, effects for both have been quite limited so far and no country has succeeded in fighting the obesity epidemy we are facing. Normalization of body weight before onset of puberty is crucial for several reasons: First, obese children and adolescents frequently stay obese until adulthood. Second, obesity during adolescence is significantly associated with increased risk for cardiovascular and metabolic disease such as type 2 diabetes in adulthood. And third, recent data have shown a strong association between higher body mass index (BMI) during adolescence and increased risk for several malignancies such as leukemia, Hodgkin's disease, colorectal cancer, breast cancer and others in adulthood. This review summarizes our current understanding of epidemiology, underlying factors, concomitant disease, as well as available intervention strategies and gives an overview of what has been reached so far and what measures should be undertaken to counteract the obesogenic environment.
10.1016/j.metabol.2018.12.001
Prevention and treatment of childhood and adolescent obesity: a systematic review of meta-analyses.
Psaltopoulou Theodora,Tzanninis Stamatios,Ntanasis-Stathopoulos Ioannis,Panotopoulos George,Kostopoulou Myrto,Tzanninis Ioannis-Georgios,Tsagianni Anastasia,Sergentanis Theodoros N
World journal of pediatrics : WJP
BACKGROUND:The goal of this systematic review is to synthesize the published meta-analyses assessing the role of nutritional, behavioral and physical activity factors/interventions on the prevention or treatment of pediatric and adolescent obesity. METHODS:An online search was conducted in PubMed (end-of-search: September 30, 2015); English-language meta-analyses pooling observational and/or interventional studies examining weight-related indices on children and adolescents were included. RESULTS:Sixty-six meta-analyses corresponding to more than 900,000 children and adolescents were retrieved. The majority of meta-analyses included interventional studies most of which referred to mixed or combined interventions, including components such as diet, physical activity and sedentary behavior reduction. Discrepancies between meta-analyses on observational and interventional studies were noted. Combined interventions including physical activity and nutritional modifications seemed to represent the most effective means for tackling childhood obesity. CONCLUSIONS:Synthesis of interventional or observational evidence may yield discrepant results. The combination of enhanced physical activity and improved nutrition emerged as a promising intervention in the fight against childhood/adolescent obesity. However, further research is needed about the most effective multidimensional prevention strategy.
10.1007/s12519-019-00266-y
Epidemic obesity in children and adolescents: risk factors and prevention.
Lee Eun Young,Yoon Kun-Ho
Frontiers of medicine
The prevalence of obesity among children and adolescents (aged 2-18 years) has increased rapidly, with more than 100 million affected in 2015. Moreover, the epidemic of obesity in this population has been an important public health problem in developed and developing countries for the following reasons. Childhood and adolescent obesity tracks adulthood obesity and has been implicated in many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease. Furthermore, childhood and adolescent obesity is linked to adulthood mortality and premature death. Although an imbalance between caloric intake and physical activity is a principal cause of childhood and adolescent obesity, environmental factors are exclusively important for development of obesity among children and adolescents. In addition to genetic and biological factors, socioenvironmental factors, including family, school, community, and national policies, can play a crucial role. The complexity of risk factors for developing obesity among children and adolescents leads to difficulty in treatment for this population. Many interventional trials for childhood and adolescent obesity have been proven ineffective. Therefore, early identification and prevention is the key to control the global epidemic of obesity. Given that the proportion of overweight children and adolescents is far greater than that of obesity, an effective prevention strategy is to focus on overweight youth, who are at high risk for developing obesity. Multifaceted, comprehensive strategies involving behavioral, psychological, and environmental risk factors must also be developed to prevent obesity among children and adolescents.
10.1007/s11684-018-0640-1
Prevention and Management of Childhood Obesity and Its Psychological and Health Comorbidities.
Annual review of clinical psychology
Childhood obesity has become a global pandemic in developed countries, leading to a host of medical conditions that contribute to increased morbidity and premature death. The causes of obesity in childhood and adolescence are complex and multifaceted, presenting researchers and clinicians with myriad challenges in preventing and managing the problem. This article reviews the state of the science for understanding the etiology of childhood obesity, the preventive interventions and treatment options for overweight and obesity, and the medical complications and co-occurring psychological conditions that result from excess adiposity, such as hypertension, nonalcoholic fatty liver disease, and depression. Interventions across the developmental span, varying risk levels, and service contexts (e.g.,community, school, home, health care systems) are reviewed. Future directions for research are offered with an emphasis on translational issues for taking evidence-based interventions to scale in a manner that will reduce the public health burden of the childhood obesity pandemic.
10.1146/annurev-clinpsy-100219-060201
Treatment of adolescent obesity.
Steinbeck Katharine S,Lister Natalie B,Gow Megan L,Baur Louise A
Nature reviews. Endocrinology
The increased prevalence of adolescent obesity and associated short-term and long-term complications emphasize the need for effective treatment. In this Review, we aim to describe the evidence for, and elements of, behaviour management and adjunctive therapies and highlight the opportunities and challenges presented by obesity management in adolescence. The broad principles of treatment include management of obesity-associated complications; a developmentally appropriate approach; long-term behaviour modification (dietary change, increased physical activity, decreased sedentary behaviours and improved sleep patterns); long-term weight maintenance strategies; and consideration of the use of pharmacotherapy, more intensive dietary therapies and bariatric surgery. Bariatric surgery should be considered in those with severe obesity and be undertaken by skilled bariatric surgeons affiliated with teams experienced in the medical and psychosocial management of adolescents. Adolescent obesity management strategies are more reliant on active participation than those for childhood obesity and should recognize the emerging autonomy of the patient. The challenges in adolescent obesity relate primarily to the often competing demands of developing autonomy and not yet having attained neurocognitive maturity.
10.1038/s41574-018-0002-8
Adolescent Obesity: Diet Quality, Psychosocial Health, and Cardiometabolic Risk Factors.
Ruiz Lyndsey D,Zuelch Michelle L,Dimitratos Sarah M,Scherr Rachel E
Nutrients
Obesity is a multifaceted chronic condition with several contributing causes, including biological risk factors, socioeconomic status, health literacy, and numerous environmental influences. Of particular concern are the increasing rates of obesity in children and adolescents, as rates of obesity in youth in the United States have tripled within the last three decades. Youth from historically disadvantaged backgrounds tend to have higher rates of obesity compared to other groups. Adolescents often do not meet intake recommendations for certain food groups and nutrients, which may contribute to a heightened risk of obesity. With obesity disproportionately affecting adolescents (ages 12-19 years), negative effects of excess adiposity may be particularly salient during this critical period of development. The presentation of chronic cardiometabolic disease symptoms typically observed in adults, such as hypertension, hyperglycemia, dyslipidemia, and inflammation, are becoming increasingly common in adolescents with obesity. Additionally, there is dynamic interplay between obesity and psychosocial health, as adolescents with obesity may have increased levels of stress, depressive symptoms, and reduced resilience. To reduce and prevent adolescent obesity, the implementation of theory-driven multicomponent school- and community-based interventions have been suggested. These interventions promote knowledge and self-efficacy for healthful practices that have the potential to progress to sustained behavior change.
10.3390/nu12010043
Obesity in children and adolescents: epidemiology, causes, assessment, and management.
The lancet. Diabetes & endocrinology
This Review describes current knowledge on the epidemiology and causes of child and adolescent obesity, considerations for assessment, and current management approaches. Before the COVID-19 pandemic, obesity prevalence in children and adolescents had plateaued in many high-income countries despite levels of severe obesity having increased. However, in low-income and middle-income countries, obesity prevalence had risen. During the pandemic, weight gain among children and adolescents has increased in several jurisdictions. Obesity is associated with cardiometabolic and psychosocial comorbidity as well as premature adult mortality. The development and perpetuation of obesity is largely explained by a bio-socioecological framework, whereby biological predisposition, socioeconomic, and environmental factors interact together to promote deposition and proliferation of adipose tissue. First-line treatment approaches include family-based behavioural obesity interventions addressing diet, physical activity, sedentary behaviours, and sleep quality, underpinned by behaviour change strategies. Evidence for intensive dietary approaches, pharmacotherapy, and metabolic and bariatric surgery as supplemental therapies are emerging; however, access to these therapies is scarce in most jurisdictions. Research is still needed to inform the personalisation of treatment approaches of obesity in children and adolescents and their translation to clinical practice.
10.1016/S2213-8587(22)00047-X
Factors associated with weight gain during olanzapine treatment in patients with schizophrenia or bipolar disorder: results from a six-month prospective, multinational, observational study.
Treuer Tamás,Hoffmann Vicki Poole,Chen Antony Kuang-Peng,Irimia Victoria,Ocampo Magdalena,Wang Gang,Singh Pritibha,Holt Susanna
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
The aim of this 6-month observational study was to examine which clinical, eating- and lifestyle-related factors were associated with weight gain in patients initiating or switching to oral olanzapine for the treatment of schizophrenia or bipolar mania. A total of 622 outpatients in four countries (China, Mexico, Romania, Taiwan) were assessed at monthly intervals for up to 6 months. Mixed model repeated-measures analysis, adjusted for baseline weight, was used to identify which factors were associated with weight gain during olanzapine therapy. After 6 months of therapy, the LS mean weight change was +4.1 kg and 43.9% of the patients had significant (> or = 7%) weight gain. Early significant weight gain after 2 months of therapy occurred in 23.4% of the patients and these patients gained significantly more weight overall. Ten factors were associated with weight gain during 6 months of olanzapine therapy in an exploratory multivariate analysis: country, housing conditions, stronger appetite, excessive amount of food needed to feel full, eating until uncomfortably full, thoughts preoccupied with food, meal location, increased meal frequency, evening snack consumption, and a lower amount of vigorous exercise. These results indicate that the influence of environmental, eating- and lifestyle-related factors should be considered when assessing weight gain during olanzapine therapy.
10.1080/15622970903079507
Prevalence of metabolic syndrome in bipolar patients initiating acute-phase treatment: a 6-month follow up.
Guan Nianhong,Liu Hairen,Diao Feici,Zhang Jinbei,Zhang Ming,Wu Tingjuan
Psychiatry and clinical neurosciences
AIMS:To evaluate the prevalence of metabolic syndrome (MetS) and its correlates in patients with bipolar disorder (BD) during acute-phase treatment in southern China. METHODS:This study included 148 BD patients presenting with acute mood symptoms and 65 healthy controls at entry. Sociodemographic characteristics were noted for all participants. For patients, lifestyle information (alcohol, smoking, and exercise habits) and clinical characteristics were also collected. Patients were followed up for 6 months after the commencement of pharmacological treatment. Using the Chinese Medical Association Diabetes Branch criteria, MetS prevalence rates were calculated at entry and recalculated for patients at months 1, 3, and 6. RESULTS:At baseline, MetS was presented in 11.5% of the patients; overweight, 34.5%; low high-density lipoprotein cholesterol, 15.5%; hypertriglyceridemia, 29.1%; hypertension, 14.9%; and hyperglycemia, 5.4%. Compared with controls, the patients had a significantly higher prevalence of MetS and all its components except for hyperglycemia (P < 0.05). In the regression analysis, history of hypertension, presence of diabetes, and alcohol drinking were associated with MetS. During the follow-up period, rates of MetS and overweight increased gradually and stably, hypertriglyceridemia and low high-density lipoprotein cholesterol increased significantly in the first month and then remained stable, and hypertension and hyperglycemia remained stable all the time. CONCLUSIONS:These data show that MetS is highly prevalent in Chinese BD patients. Weight gain and dyslipidemia result from a short period of treatment. Early interventions for weight gain and dyslipidemia are warranted.
10.1111/j.1440-1819.2010.02150.x
The effects of antipsychotic medications on microbiome and weight gain in children and adolescents.
Bretler Tali,Weisberg Hagar,Koren Omry,Neuman Hadar
BMC medicine
BACKGROUND:Atypical antipsychotics, also known as second-generation antipsychotics, are commonly prescribed as treatment for psychotic disorders in adults, as well as in children and adolescents with behavioral problems. However, in many cases, second-generation antipsychotics have unwanted side effects, such as weight gain, potentially further increasing risk for morbidities including obesity, diabetes, and cardiovascular disease. While various mechanisms for this weight gain have been proposed, including effects on metabolic hormone signaling, recent evidence points to the importance of the gut microbiome in this process. The microbial communities residing within the gut are affected by second-generation antipsychotics and can confer weight gain. MAIN TEXT:This review summarizes recent findings and presents data linking second-generation antipsychotics, gut microbiota alterations and weight gain. The review focuses on children and adolescent populations, which have not previously received much attention, but are of great interest because they may be most vulnerable to gut microbiome changes and may carry long-term metabolic effects into adulthood. CONCLUSIONS:We present correlations between second-generation antipsychotics, gut microbiota alterations and weight gain, and suggest some mechanisms that may link them. A better understanding of the underlying mechanisms may lead to the design of improved treatments for psychotic disorders with fewer harmful side effects.
10.1186/s12916-019-1346-1
Effects of Berberine on Gut Microbiota in Patients with Mild Metabolic Disorders Induced by Olanzapine.
Pu Zhengping,Sun Yunying,Jiang Hongxia,Hou Qingmei,Yan Hui,Wen Hui,Li Guorong
The American journal of Chinese medicine
Secondary metabolic disturbances in patients with schizophrenia or bipolar disorder may be attributed to olanzapine. It is important to prevent mild metabolic disorders progressing to metabolic syndrome. This study aims to investigate the effects of berberine on intestinal flora in patients with mild metabolic disorders induced by olanzapine. A total of 132 patients with schizophrenia, bipolar disorder, or schizoaffective psychosis that had been treated with olanzapine for at least 9 months were randomly assigned ([Formula: see text] = 66 each) to receive berberine or placebo tablets for 12 weeks. Metabolic assessments and intestinal flora were quantified at baseline and after 4, 8, and 12 weeks of treatment. Incidence rates of adverse reactions were recorded. FPG, FPI, HOMA-IR, HbA1, TG, BMI, and WC were significantly lower in patients who received berberine compared to placebo after 12 weeks of treatment ([Formula: see text]< 0.05). The abundance of firmicutes and coliform were significantly lower and the abundance of bacteroides significantly higher in patients who received berberine compared to placebo after 12 weeks of treatment ([Formula: see text]< 0.05). In patients who received berberine, the abundance of firmicutes was significantly decreased, and the abundance of bacteroides was significantly increased, and in patients who received placebo, the abundance of firmicutes was significantly increased post-treatment, compared to baseline (both [Formula: see text]< 0.05). In conclusions, berberine may regulate intestinal flora and metabolism in patients with schizophrenia or bipolar disorder and mild metabolic disturbances induced by olanzapine.
10.1142/S0192415X21500920
Ziziphi spinosae lily powder suspension in the treatment of depression-like behaviors in rats.
Wang Yifang,Huang Mei,Lu Xinyi,Wei Runze,Xu Jinyong
BMC complementary and alternative medicine
BACKGROUND:Depression is a chronic, recurring and potentially life-threatening illness. Current treatments for depression are characterized by a low success rate and associated with a wide variety of side effects. The aim of the present study was to evaluate the behavioral anti-depressant effect of a novel herbal compounds named ziziphi spinosae lily powder suspension, as well as to investigate its potential mechanisms. METHODS:Except for body weight, depressive-like behaviors were also evaluated using forced swimming test, sucrose consumption test and open field test. In order to investigate the underlying potential mechanisms, serum 5-HT and brain 5-HIAA were measured using ultrahigh-performance liquid chromatography and high-performance liquid chromatography, respectively. RESULTS:Results showed that the herbal compounds ziziphi spinosae lily suspension could alleviate depressive symptoms in rat model of chronic depression. Biochemical analysis revealed that the herbal compounds elevated serum 5-HT and brain 5-HIAA. CONCLUSION:Ziziphi spinosae lily powder suspension could alleviate depressive behaviors in depression model animals. The underlying mechanisms may be related to the increase of serum 5-HT in peripheral blood and 5-HIAA in brain. The study provides important mechanistic insights into the protective effect of the herbal compounds against chronic depressive disorder and suggests that the herbal compounds may be a potential pharmacological agent for treatment of major depressive disorder.
10.1186/s12906-017-1749-5
Vanillin-induced amelioration of depression-like behaviors in rats by modulating monoamine neurotransmitters in the brain.
Xu Jinyong,Xu Hui,Liu Yang,He Haihui,Li Guangwu
Psychiatry research
Olfaction plays an important role in emotions in our daily life. Pleasant odors are known to evoke positive emotions, inducing relaxation and calmness. The beneficial effects of vanillin on depressive model rats were investigated using a combination of behavioral assessments and neurotransmitter measurements. Before and after chronic stress condition (or olfactory bulbectomy), and at the end of vanillin or fluoxetine treatment, body weight, immobility time on the forced swimming test and sucrose consumption in the sucrose consumption test were measured. Changes in these assessments revealed the characteristic phenotypes of depression in rats. Neurotransmitters were measured using ultrahigh-performance liquid chromatography. Our results indicated that vanillin could alleviate depressive symptoms in the rat model of chronic depression via the olfactory pathway. Preliminary analysis of the monoamine neurotransmitters revealed that vanillin elevated both serotonin and dopamine levels in brain tissue. These results provide important mechanistic insights into the protective effect of vanillin against chronic depressive disorder via olfactory pathway. This suggests that vanillin may be a potential pharmacological agent for the treatment of major depressive disorder.
10.1016/j.psychres.2014.11.056
Associations Between Serum Folate Level and HOMA-IR in Chinese Patients with Type 2 Diabetes Mellitus.
Diabetes, metabolic syndrome and obesity : targets and therapy
Background:Adequate intake of folic acid (FA) has been proven essential for metabolism, cellular homeostasis, and antioxidant effects in diabetic patients. Our aim was to evaluate the association between serum folate levels and the risk of insulin resistance in patients with type 2 diabetes mellitus (T2DM) and to provide new ideas and approaches for reducing the risk of T2DM. Methods:This was a case-control study involving 412 participants (206 with T2DM). Anthropometric parameters, islet function, biochemical parameters and body composition of T2DM group and control group were determined. Correlation analysis and logistic regression were used to evaluate the risk factors associated with the onset of insulin resistance in T2DM. Results:The folate levels in type 2 diabetic patients with insulin resistance were significantly lower than those in patients without insulin resistance. Logistic regression showed that FA and high-density lipoprotein were independent influencing factors for insulin resistance in diabetic patients ( < 0.05). After adjusting for confounding factors, the degree of insulin resistance in diabetic patients was in a significant inverse relationship with folate levels (< 0.05). We also found that below the serum FA threshold of 7.09 ng/mL insulin resistance was significantly more elevated. Conclusion:Our findings suggest that the risk of insulin resistance increases with the decrease in serum FA levels in T2DM patients. Monitoring folate levels in these patients and FA supplementation are warranted preventive measures.
10.2147/DMSO.S409291
The prevalence and clinical correlates of medical disorders comorbidities in patients with bipolar disorder.
BMC psychiatry
OBJECTIVE:Medical disorders in patients with bipolar disorder (BD) have attracted more and more attention. So far, there is still a lack of studies on this issue utilizing large sample sizes in the Chinese sample. Therefore, we conducted this study to explore the clinical characteristics of BD patients comorbid medical disorders in a relatively large Chinese sample. METHODS:This was a cross-sectional study including 1,393 BD patients (882 patients with medical disorders and 511 patients without medical disorders). Their demographic and clinical characteristics were obtained by the Hospital Information System and self-designed questionnaires. RESULTS:The comorbidity rate of medical disorders in BD was 63.32%. The average number of medical disorders for a BD patient was 2.69. The top five comorbid medical disorders in BD patients were circulatory system diseases (19%), nervous system diseases (18%), endocrine and metabolic diseases (17%), digestive system diseases (16%), and respiratory system diseases (8%). BD patients with comorbid medical disorders had an older average age, lower education level, longer illness course, later onset age, lower ratio of psychotic features, more admission numbers, higher ratio of smoking and drinking alcohol, more number of manic episodes (All P < 0.05). Smoking, numbers of depressive episode, onset age, and illness course were independent risk factors of comorbidities in BD patients (All P < 0.05). CONCLUSIONS:Medical disorders in Chinese BD patients are highly prevalent. The smoking, number of depressive episodes, onset age, illness course, are correlated with BD patients comorbid medical disorders. Clinicians should pay attention to the medical disorders comorbidities in BD patients, and take effective measures to improve treatment outcome and reduce the suffering. The integrative approach should be the imperative in clinical practice.
10.1186/s12888-022-03819-0
Mechanisms Underlying Antipsychotic-Induced NAFLD and Iron Dysregulation: A Multi-Omic Approach.
Biomedicines
Atypical antipsychotic (AA) medications are widely prescribed for the treatment of psychiatric disorders, including schizophrenia, bipolar disorder and treatment-resistant depression. AA are associated with myriad metabolic and endocrine side effects, including systemic inflammation, weight gain, dyslipidemia and insulin resistance, all of which are associated with increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is highly prevalent in patients with mental illness, and AA have been shown to increase incidence of NAFLD pre-clinically and clinically. However, the underlying mechanisms have not been described. We mined multi-omic datasets from preclinical murine models of sub-chronic risperidone or olanzapine treatment, in vitro exposure of human cells to risperidone and psychiatric patients following onset of aripiprazole therapy focused on pathways associated with the pathophysiology of NAFLD, including iron accumulation, systemic inflammation and dyslipidemia. We identified numerous differentially expressed traits affecting these pathways conserved across study systems and AA medications. We used these findings to propose mechanisms for AA-associated development of NAFLD and dysregulated iron homeostasis.
10.3390/biomedicines10061225
Oxytocin in Schizophrenia: Pathophysiology and Implications for Future Treatment.
Goh Kah Kheng,Chen Chun-Hsin,Lane Hsien-Yuan
International journal of molecular sciences
Schizophrenia is a form of mental disorder that is behaviorally characterized by abnormal behavior, such as social function deficits or other behaviors that are disconnected from reality. Dysregulation of oxytocin may play a role in regulating the expression of schizophrenia. Given oxytocin's role in social cognition and behavior, a variety of studies have examined the potential clinical benefits of oxytocin in improving the psychopathology of patients with schizophrenia. In this review, we highlight the evidence for the role of endogenous oxytocin in schizophrenia, from animal models to human studies. We further discuss the potential of oxytocin as a therapeutic agent for schizophrenia and its implication in future treatment.
10.3390/ijms22042146
Altered functional connectivity of right inferior frontal gyrus subregions in bipolar disorder: a resting state fMRI study.
Zhang Li,Li Wenfei,Wang Long,Bai Tongjian,Ji Gong-Jun,Wang Kai,Tian Yanghua
Journal of affective disorders
The right inferior frontal gyrus (rIFG) is a key cortical node in the circuits of emotion and cognitive control, and it has been frequently associated with bipolar disorder (BP); however, a reliable pattern of aberrant rIFG activation and connectivity in bipolar disorder has yet to be established. To further elucidate rIFG abnormalities in different states of bipolar disorder, we examined activation and functional connectivity (FC) in five subregions of rIFG in bipolar disorder. A total of 83 participants, including those with bipolar depression (BPD; n = 25) and bipolar mania (BPM; n = 37) along with healthy control (HC) subjects (n = 26), were examined by resting state functional magnetic resonance imaging (rs-fMRI). Both BPD and BPM groups showed higher values of amplitude of low-frequency fluctuations (ALFF) than healthy control in four of the five rIFG subregions except cluster 2(posterior-ventral rIFG). Using five subregions of rIFG as seeds, the decreased FC in bipolar disorder was mainly between posterior-ventral rIFG(cluster 2) and multiple brain regions including the postcentral gyrus, the precentral gyrus, paracentral lobule, lingual Gyrus, fusiform and cerebellum posterior lobe. These results indicated that local activity and FC were altered within specific subregions of the rIFG in BP. These findings may provide the distinct functional connectivity of rIFG subregions in BP and suggest that the cluster2 (posterior-ventral rIFG) circuitry plays a crucial role in BP. Also, such abnormalities might help define a more precise intervention targets.
10.1016/j.jad.2020.03.122
Effects of smartphone-based interventions and monitoring on bipolar disorder: A systematic review and meta-analysis.
Liu Jia-Yuan,Xu Kang-Kang,Zhu Guang-Lin,Zhang Qi-Qi,Li Xiao-Ming
World journal of psychiatry
BACKGROUND:Recently, there has been a range of studies about smartphone-based interventions and monitoring for reducing symptoms of bipolar disorder (BD). However, their efficacy for BD remains unclear. AIM:To compare the effect of smartphone-based interventions and monitoring with control methods in treating patients with BD. METHODS:A systematic literature search was performed on PubMed, Embase, Clinical trials, psycINFO, Web of Science, and Cochrane Library. Randomized clinical trials (RCTs) or single-group trials in which smartphone-based interventions and monitoring were compared with control methods or baseline in patients with symptoms of BD were included. Data were synthesized using a random-effects or a fixed-effects model to analyze the effects of psychological interventions and monitoring delivered smartphone on psychiatric symptoms in patients with BD. The primary outcome measures were set for mania and depression symptoms. Subgroups were created to explore which aspects of smartphone interventions are relevant to the greater or lesser efficacy of treating symptoms. RESULTS:We identified ten articles, including seven RCTs (985 participants) and three single-group trials (169 participants). Analysis of the between-group study showed that smartphone-based interventions were effective in reducing manic [g = -0.19, 95% confidence interval (CI): -0.33 to -0.04, = 0.01] and depressive (g = -0.28, 95%CI: -0.55 to -0.01, < 0.05) symptoms. In within-group analysis, smartphone-based interventions significantly reduced manic (g = 0.17, 95%CI: 0.04 to 0.30, < 0.01) and depressive (g = 0.48, 95%CI: 0.18 to 0.78) symptoms compared to the baseline. Nevertheless, smartphone-based monitoring systems significantly reduced manic (g = 0.27, 95%CI: 0.02 to 0.51, < 0.05) but not depressive symptoms. Subgroup analysis indicated that the interventions with psychoeducation had positive effects on depressive (g = -0.62, 95%CI: -0.81 to -0.43, P < 0.01) and manic (g = -0.24, 95%CI: -0.43 to -0.06, = 0.01) symptoms compared to the controlled conditions, while the interventions without psychoeducation did not ( > 0.05). The contacts between therapists and patients that contributed to the implementation of psychological therapy reduced depression symptoms (g = -0.47, 95%CI: -0.75 to -0.18, = 0.01). CONCLUSION:Smartphone-based interventions and monitoring have a significant positive impact on depressive and manic symptoms of BD patients in between-group and within-group analysis.
10.5498/wjp.v10.i11.272
Non-enzymatic antioxidants, macro-minerals and monocyte/high-density lipoprotein cholesterol ratio among patients with bipolar disorder.
Journal of affective disorders
OBJECTIVE:Recent studies show that oxidative stress is related to the pathogenesis of BD. Non-enzymatic antioxidants, macro-minerals and MHR (monocyte divided by high-density lipoprotein cholesterol) participated oxidative stress and can be obtained quickly in hematological examination. This study used large-scale clinical data to investigate them between BD and healthy controls (HCs), as well as between psychotic and non-psychotic BD to explore their roles in disease progression. METHODS:A total of 3442 BD-manic (BD-M) and 1405 BD-depression (BD-D) in acute stage and 5000 HCs were enrolled, including 1592 BD-M with psychotic symptoms (P-BD-M), 1850 BD-M without psychotic symptoms (NP-BD-M), 655 P-BD-D, 750 NP-BD-D. The differences in these biological parameter levels among different groups were compared, and the contributing factors for the occurrence of BD-M or BD-D and psychotic symptoms of BD were analyzed. RESULTS:We found higher levels of Na and MHR, and lower levels of K, Ca and ALB in BD-M or BD-D compared with the HCs respectively; levels of K, Na, Ca, ALB and MHR have differences among P-BD-M, NP-BD-M and HC; levels of K, Na, Ca and ALB have differences among P-BD-D, NP-BD-D and HC. In multiple logistic regression, higher levels of MHR and Na were associated with BD-M; MHR was shown to be independently associated with P-BD-M; K, Na, ALB were shown to be independently associated with P-BD-D. CONCLUSIONS:Our study highlights the role of oxidative stress in the pathophysiology of BD. There is heterogeneity between BD-M and BD-D, and different oxidative stress mechanisms of psychotic symptoms exist in BD-M and BD-D.
10.1016/j.jad.2022.11.017
Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder.
Frontiers in psychiatry
Background:The systemic immune-inflammation index (SII), system inflammation response index (SIRI), neutrophil/high-density lipoprotein (HDL) ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR), and platelet/HDL ratio (PHR) have been recently investigated as new markers for inflammation. The purpose of this research is to use large-scale clinical data to discuss and compare the predictive ability of the SII, SIRI, NHR, LHR, MHR, and PHR in patients with schizophrenia (SCZ) and bipolar disorder (BD), to investigate potential biomarkers. Materials and methods:In this retrospective, naturalistic, cross-sectional study, we collected the hematological parameter data of 13,329 patients with SCZ, 4,061 patients with BD manic episodes (BD-M), and 1,944 patients with BD depressive episodes (BD-D), and 5,810 healthy subjects served as the healthy control (HC) group. The differences in the SII, SIRI, NHR, LHR, MHR, and PHR were analyzed, and a receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these parameters. Results:Compared with the HC group, the values of the SII, SIRI, NHR, LHR, MHR, and PHR and the levels of neutrophils, monocytes, and triglycerides (TG) were higher in SCZ and BD groups, and levels of platelets, cholesterol (CHO), HDL, low-density lipoprotein (LDL), and apoprotein B (Apo B) were lower in SCZ and BD groups. Compared to the BD group, the values of the SIRI, lymphocytes, monocytes, and HDL were lower and the values of the SII, NHR, PHR, and platelet were higher in the SCZ group. In contrast to the BD-D group, the values of the SII; SIRI; NHR; and MHR; and levels of neutrophils, monocytes, and platelets were higher in the BD-M group, and the levels of CHO, TG, LDL, and Apo B were lower in the BD-M group. The MHR and NHR were predictors for differentiating the SCZ group from the HC group; the SIRI, NHR, and MHR were predictors for differentiating the BD-M group from the HC group; and the MHR was a predictor for differentiating the BD-D group from the HC group. The combination model of the indicators improved diagnostic effectiveness. Conclusion:Our study highlights the role of systemic inflammation in the pathophysiology of SCZ, BD-M, and BD-D, the association between inflammation and lipid metabolism, and these inflammation and lipid metabolism indicators showed different variation patterns in SCZ, BD-D, and BD-M.
10.3389/fpsyt.2022.941728
Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis.
Vancampfort Davy,Stubbs Brendon,Mitchell Alex J,De Hert Marc,Wampers Martien,Ward Philip B,Rosenbaum Simon,Correll Christoph U
World psychiatry : official journal of the World Psychiatric Association (WPA)
Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta-analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%-34.4%; N = 198; n = 52,678). Relative risk meta-analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta-analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = -3.6, p = 0.0003, r(2) = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic-naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35-1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.
10.1002/wps.20252
Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics.
Cernea Simona,Dima Lorena,Correll Christoph U,Manu Peter
Drugs
Fasting hyperglycemia, impaired glucose tolerance, prediabetes, and diabetes are frequently present in patients treated with second-generation antipsychotics (SGAPs) for schizophrenia, bipolar disorder, and other severe mental illnesses. These drugs are known to produce weight gain, which may lead to insulin resistance, glucose intolerance, and metabolic syndrome, which constitute important risk factors for the emergence of diabetes. The aim of this review was to formulate therapeutic guidelines for the management of diabetes in patients treated with SGAPs, based on the association between SGAP-induced weight gain and glucose dysregulation. A systematic search in PubMed from inception to March 2020 for randomized controlled trials (RCTs) of diabetes or prediabetes in patients treated with SGAPs was performed. PubMed was also searched for the most recent clinical practice guidelines of interventions for co-morbid conditions associated with diabetes mellitus (DM) (arterial hypertension and dyslipidemia), lifestyle interventions and switching from high metabolic liability SGAPs to safer SGAPs. The search identified 14 RCTs in patients treated with SGAPs. Drug therapy using metformin as first-line therapy and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or perhaps sodium-glucose cotransporter-2 (SGLT2) inhibitors as add-on therapy, might be preferred in these patients as well, as they favorably influence glucose metabolism and body mass index, and provide cardio-renal benefits in general to the DM population, although for the SGLT-2 inhibitors there are no RCTs in this specific patient category so far. Metformin is also useful for treatment of prediabetes. Arterial hypertension should be treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and statins should be used for correction of dyslipidemia. The outcome of lifestyle-changing interventions has been disappointing. Switching from clozapine, olanzapine, or quetiapine to lower cardiometabolic-risk SGAPs, like aripiprazole, brexpiprazole, cariprazine, lurasidone, or ziprasidone, has been recommended.
10.1007/s40265-020-01393-x
Metabolic Effects of 7 Antipsychotics on Patients With Schizophrenia: A Short-Term, Randomized, Open-Label, Multicenter, Pharmacologic Trial.
Zhang Yamin,Wang Qiang,Reynolds Gavin P,Yue Weihua,Deng Wei,Yan Hao,Tan Liwen,Wang Chuanyue,Yang Guigang,Lu Tianlan,Wang Lifang,Zhang Fuquan,Yang Jianli,Li Keqing,Lv Luxian,Tan Qingrong,Li Yinfei,Yu Hua,Zhang Hongyan,Ma Xin,Yang Fude,Li Lingjiang,Chen Qi,Wei Wei,Zhao Liansheng,Wang Huiyao,Li Xiaojing,Guo Wanjun,Hu Xun,Tian Yang,Ren Hongyan,Ma Xiaohong,Coid Jeremy,Zhang Dai,Li Tao,
The Journal of clinical psychiatry
OBJECTIVE:To compare longitudinal metabolic effects of 7 antipsychotics, including body mass index (BMI), waist circumference (WC), blood pressure (BP), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); to investigate risk factors for metabolic syndrome (MetS); and to make recommendations on frequency and timing of monitoring metabolic measurements. METHODS:This randomized, open-label, pharmacologic trial was conducted among patients with schizophrenia (DSM-IV) in 32 hospitals across China. Patients were randomly assigned to 7 groups and assessed at baseline, 2, 4, and 6 weeks. Linear mixed-effect models were used to assess changes of metabolic measures over time. Multivariable logistic regression analysis was performed to investigate the risk factors for MetS. RESULTS:In total, 2,550 (718 drug-naïve) of 2,774 patients finished the study between July 6, 2010, and November 30, 2011. We found significant (P < .05) changes for BMI, WC, TG, and LDL-C, with TG and LDL-C reaching a plateau. Interactions between baseline metabolic condition and changes over time were observed for BMI (χ² = 43.11, P < .001), WC (χ² = 36.34, P < .001), systolic BP (χ² = 11.92, P = .002), glucose (χ² = 6.09, P = .01), and TG (χ² = 6.01, P = .01). Antipsychotics generally had greater adverse effects on patients who were initially screened as metabolically normal. After controlling for other associated factors, we found that antipsychotics resulted in differing risk for incident MetS, with a similar pattern to findings in other populations: olanzapine (odds ratio [OR] = 3.36, P < .001) > quetiapine (OR = 3.29, P < .001) > perphenazine (OR = 2.73, P = .007) > risperidone (OR = 2.21, P = .02) > aripiprazole (OR = 1.74, P = .15) ≈ haloperidol (OR = 1.75, P = .22) ≈ ziprasidone (OR = 1, reference). CONCLUSIONS:Metabolic traits should be monitored frequently in early stages of antipsychotic treatment due to rapid and substantial changes. Clinicians should not assume low risk for patients with normal metabolic parameters at baseline. TRIAL REGISTRATION:Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000934.
10.4088/JCP.19m12785
Prevalence of metabolic syndrome among patients with schizophrenia in Ethiopia.
Challa Feyissa,Getahun Tigist,Sileshi Meron,Geto Zeleke,Kelkile Teshome S,Gurmessa Sintayehu,Medhin Girmay,Mesfin Miraf,Alemayehu Melkam,Shumet Tigist,Mulugeta Anwar,Bekele Desalegn,Borba Christina P C,Oppenheim Claire E,Henderson David C,Fekadu Abebaw,Carobene Anna,Teferra Solomon
BMC psychiatry
BACKGROUND:Globally, the prevalence of metabolic syndrome (MetS) is higher among patients with schizophrenia than the general population, and this leads to higher morbidity and mortality in this population. The aim of this study was to investigate the MetS prevalence among patients with schizophrenia in Ethiopia. METHODS:We conducted a cross-sectional analysis of baseline data of 200 patients with schizophrenia recruited from Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. Lipid profile and blood glucose levels were measured using Roche Cobas 6000 clinical chemistry analyzer. The prevalence of MetS was assessed based on National Cholesterol Education Program Adult Treatment Panel III criteria. Patients' demographic information, clinical and laboratory data, lifestyle habits, particularly smoking and Khat chewing, were evaluated vis-à-vis MetS. RESULTS:The overall prevalence of MetS in patients with schizophrenia was 21.5% (17.1% male, 29.6% female) where Low HDL-cholesterol value was the most common metabolic disorders components in both males and females subgroups. In the multivariate analysis, the positive and negative symptoms score (PANSS, AOR = 1.03, 95% CI 1.001-1.054) was associated factors with MetS. CONCLUSION:In Ethiopia, patients with schizophrenia were found to have higher prevalence of MetS than the general population. Physicians/health care providers should routinely screen patients with schizophrenia for MetS and initiate timely management of those who develop the syndrome to reduce the health cost from caring for NCDs, improve the patients' quality of life, and prevent premature mortality.
10.1186/s12888-021-03631-2
Prevalence of metabolic syndrome among patients with schizophrenia in Japan.
Sugawara Norio,Yasui-Furukori Norio,Sato Yasushi,Umeda Takashi,Kishida Ikuko,Yamashita Hakuei,Saito Manabu,Furukori Hanako,Nakagami Taku,Hatakeyama Mitsunori,Nakaji Shigeyuki,Kaneko Sunao
Schizophrenia research
AIMS:In an Asian population, the criteria for metabolic syndrome (MetS) are different from those for Western populations. The aim of this study was to assess the MetS prevalence among patients with schizophrenia or schizoaffective disorder in Japan. METHODS:We recruited patients (n=1186), aged 54.8±14.8 (mean±SD) years old with the DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to seven psychiatric hospitals using a cross-sectional design. MetS prevalence was assessed by three different definitions, including the adapted National Cholesterol Education Program Adult Treatment Panel (ATP III-A). Comparative analysis was performed with schizophrenic subjects and 886 participants from the Iwaki Health Promotion Project 2008 as representative of general population. RESULTS:The overall MetS prevalence based on the ATP III-A definition was 27.5%, with 29.8% in male and 25.3% in female patients. In a logistic regression model with age and body mass index as covariates, being schizophrenic was a significant independent factor (odds ratio=2.00 for males, 2.13 for females) in the development of MetS under the ATP III-A definition. The difference of MetS prevalence between patients and the general population was observed for those under 60 years of age. CONCLUSIONS:Patients with schizophrenia or schizoaffective disorder in Japan had high prevalence of MetS compared to the general population, and was most apparent for those under 60 years of age. The MetS in schizophrenic patients should be carefully monitored to minimize the risks.
10.1016/j.schres.2010.08.030
Cardio-metabolic risk and its management in a cohort of clozapine-treated outpatients.
Lappin Julia Margaret,Wijaya Marlene,Watkins Andrew,Morell Rachel,Teasdale Scott,Lederman Oscar,Rosenbaum Simon,Dick Stephanie,Ward Philip,Curtis Jackie
Schizophrenia research
OBJECTIVE:To comprehensively assess cardio-metabolic risk factors and their management in a large sample of outpatients treated with clozapine. METHODS:Observational cross-sectional study of all clozapine users attending specialized clozapine monitoring outpatient clinics in three public hospitals in Sydney, Australia were approached to participate over the one-year period 01/10/2015-30/09/2016. Cardio-metabolic risk factors including metabolic syndrome, risk for future development of diabetes, smoking, physical activity, nutrition, and prescribed medications were assessed at face-to-face interview and through medical record review. Among patients who had cardio-metabolic risk factors, the proportion receiving appropriate management was assessed. RESULTS:Of 451 registered clozapine clinic attenders, 92.2% completed questionnaires and anthropometric measurements. 58.3% met criteria for metabolic syndrome. 79.6% were overweight or obese. 55.9% had blood pressure meeting metabolic syndrome criteria. 46.6% had elevated fasting blood glucose and 55.2% had elevated blood triglycerides. 43.6% were current smokers. Only 10% achieved recommended weekly physical activity levels. Unhealthy food categories were highly consumed. 32.1% were on additional antipsychotics. In the majority of individuals, cardio-metabolic risk factors were untreated or under-treated. CONCLUSIONS:Clozapine use was associated with very high rates of cardiovascular and metabolic risk factors, which were frequently under-treated. Management of both physical and mental health should be prioritized. Polypharmacy should be rationalized. Future research should investigate the effectiveness of smoking cessation and lifestyle interventions in this high-risk population.
10.1016/j.schres.2018.02.035
Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction.
International journal of molecular sciences
The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.
10.3390/ijms23137092
Risk of Nonalcoholic Fatty Liver Disease in Patients With Schizophrenia Treated With Antipsychotic Drugs: A Cross-sectional Study.
Koreki Akihiro,Mori Hiroko,Nozaki Shoko,Koizumi Teruki,Suzuki Hisaomi,Onaya Mitsumoto
Journal of clinical psychopharmacology
BACKGROUND:Although the prevalence of metabolic syndrome in patients with schizophrenia is higher than the prevalence in the general population, little is known regarding nonalcoholic fatty liver disease (NAFLD) in patients with schizophrenia. PROCEDURES:We analyzed the medical records of patients with schizophrenia/schizoaffective disorder (N = 253) who received an abdominal echography. RESULTS:In total, 108 patients (42.7%) showed NAFLD on abdominal echography. Of these, 13 patients (12.0%) showed signs of fibrosis on abdominal echography. In terms of age distribution, NAFLD was more prevalent in younger patients, particularly in female patients. We also found that body mass index, the total dose of antipsychotic drugs that carry a risk of metabolic syndrome, and the total dose of antipsychotic drugs that carry a risk of hyperprolactinemia were significantly associated with NAFLD (P < 0.001, 0.049, and 0.041, respectively). In our exploratory analysis, we found that signs of fibrosis in NAFLD were more highly associated with female patients (P = 0.023). Importantly, the risk in younger female patients may be specific to patients with schizophrenia compared with the general population. CONCLUSIONS:Considering that antipsychotic drugs were associated with the development of NAFLD, early detection and management of NAFLD should be conducted in patients with schizophrenia.
10.1097/JCP.0000000000001421
The effect of sleep on gastrointestinal functioning in common digestive diseases.
Orr William C,Fass Ronnie,Sundaram Shikha S,Scheimann Ann O
The lancet. Gastroenterology & hepatology
Sleep quality and sleep disorders affect symptom manifestation and the pathogenesis of digestive diseases. Sleep is largely regulated by the light-dark cycle and associated circadian rhythms. These occurrences are closely regulated through several mechanisms with direct effects on the gastrointestinal tract. Misalignment of the circadian system is a common cause of sleep complaints, which play an important role in the presentation of many gastrointestinal disorders. This Review will focus on sleep disorders and how these alterations in sleep play an important role in many commonly encountered digestive diseases, such as gastro-oesophageal reflux disease, irritable bowel syndrome, inflammatory bowel disease, and non-alcoholic fatty liver disease. Therapeutic interventions focusing on resolving sleep disorders could optimise treatment and improve quality of life in these patients.
10.1016/S2468-1253(19)30412-1
The genetics of bipolar disorder with obesity and type 2 diabetes.
Journal of affective disorders
BACKGROUND:Bipolar disorder (BD) presents with high obesity and type 2 diabetes (T2D) and pathophysiological and phenomenological abnormalities shared with cardiometabolic disorders. Genomic studies may help define if they share genetic liability. This selective review of BD with obesity and T2D will focus on genomic studies, stress their current limitations and guide future steps in developing the field. METHODS:We searched electronic databases (PubMed, Scopus) until December 2021 to identify genome-wide association studies, polygenic risk score analyses, and functional genomics of BD accounting for body mass index (BMI), obesity, or T2D. RESULTS:The first genome-wide association studies (GWAS) of BD accounting for obesity found a promising genome-wide association in an intronic gene variant of TCF7L2 that was further replicated. Polygenic risk scores of obesity and T2D have also been associated with BD, yet, no genetic correlations have been demonstrated. Finally, human-induced stem cell studies of the intronic variant in TCF7L2 show a potential biological impact of the products of this genetic variant in BD risk. LIMITATIONS:The narrative nature of this review. CONCLUSIONS:Findings from BD GWAS accounting for obesity and their functional testing, have prompted potential biological insights. Yet, BD, obesity, and T2D display high phenotypic, genetic, and population-related heterogeneity, limiting our ability to detect genetic associations. Further studies should refine cardiometabolic phenotypes, test gene-environmental interactions and add population diversity.
10.1016/j.jad.2022.06.084
Correlates of overweight and obesity in 644 patients with bipolar disorder.
McElroy Susan L,Frye Mark A,Suppes Trisha,Dhavale Dawn,Keck Paul E,Leverich Gabriele S,Altshuler Lori,Denicoff Kirk D,Nolen Willem A,Kupka Ralph,Grunze Heinz,Walden Jorg,Post Robert M
The Journal of clinical psychiatry
OBJECTIVE:Overweight and obesity are common clinical problems encountered in the treatment of bipolar disorder. We therefore assessed the prevalence and clinical correlates of overweight, obesity, and extreme obesity in 644 bipolar patients. METHOD:644 outpatients with DSM-IV bipolar disorder in the Stanley Foundation Bipolar Treatment Outcomes Network were evaluated with structured diagnostic interviews and clinician- and self-administered questionnaires to determine bipolar disorder diagnoses, demographic and historical illness characteristics, comorbid Axis I diagnoses, medical histories, health habits, and body mass indices (BMMs). RESULTS:Fifty-eight percent of the patients with bipolar disorder were overweight, 21% were obese, and 5% were extremely obese. American patients had significantly higher mean (p < .0001) BMIs and significantly higher rates of obesity (p < .001) and extreme obesity (p < .001) than European patients. Significant associations (p < or = .001) were found between overweight, obesity. and extreme obesity and gender, age, income level, comorbid binge-eating disorder, hypertension, arthritis, diabetes mellitus, exercise habits, and coffee consumption. Current BMI and weight were each correlated with the number of weight gain-associated psychotropics to which patients had been exposed. Multinomial logistic regression (adjusted for site and eating disorder diagnosis and corrected for multiple comparisons) showed that (1) overweight was significantly associated with male gender and hypertension (p < .001), (2) obesity was significantly associated with hypertension (p < .001), and (3) extreme obesity was significantly associated with hypertension and arthritis (p < .001). CONCLUSION:Overweight, obesity, and extreme obesity were common in this group of bipolar patients, although it was unclear that their prevalence rates were truly elevated, because overweight and obesity are increasingly common public health problems among the general population. Correlates of overweight and obesity in bipolar disorder include patient and treatment variables such as gender, geographical location, comorbid binge-eating disorder, age, income level, degree of exposure to weight gain-associated psychotropics, medical disorders associated with obesity, and health habits.
Preliminary findings regarding overweight and obesity in pediatric bipolar disorder.
Goldstein Benjamin I,Birmaher Boris,Axelson David A,Goldstein Tina R,Esposito-Smythers Christianne,Strober Michael A,Hunt Jeffrey,Leonard Henrietta,Gill Mary Kay,Iyengar Satish,Grimm Colleen,Yang Mei,Ryan Neal D,Keller Martin B
The Journal of clinical psychiatry
OBJECTIVE:Overweight/obesity is highly prevalent among adults with bipolar disorder and has been associated with illness severity. Little is known regarding overweight/obesity among youth with bipolar disorder. METHOD:Subjects were 348 youths aged 7 to 17 years who met DSM-IV criteria for bipolar I or bipolar II disorder or study-operationalized criteria for bipolar disorder not otherwise specified and were enrolled in the Course and Outcome of Bipolar Illness in Youth study. Age- and sex-adjusted body mass index was computed according to International Obesity Task Force cut points, based on self- and parent-reported height and weight, to determine overweight/obesity. The study was conducted from October 2000 to July 2006. RESULTS:Overweight/obesity was prevalent among 42% of subjects. The most robust predictors of overweight/obesity in a logistic regression model were younger age, nonwhite race, lifetime physical abuse, substance use disorders, psychiatric hospitalizations, and exposure to ≥ 2 medication classes associated with weight gain. CONCLUSIONS:The prevalence of overweight/obesity among youth with bipolar disorder may be modestly greater than in the general population. Moreover, similar to adults, overweight/obesity among youth with bipolar disorder may be associated with increased psychiatric burden. These preliminary findings underscore the importance of early identification of overweight/obesity among youth with bipolar disorder. Future studies are needed to clarify the direction of the associations between overweight/obesity and the identified predictors and to compare the prevalence of overweight/obesity among youth with bipolar disorder versus other psychiatric disorders.
10.4088/jcp.v69n1215
The bi-directional association between bipolar disorder and obesity: Evidence from Meta and bioinformatics analysis.
International journal of obesity (2005)
BACKGROUND:The globally high prevalence of both obesity and bipolar disorder makes the bidirectional relationship between the two disorders a pivotal phenomenon; hence, a meta-analysis to synopsize their co-occurrence is indispensable. Psychotropic-induced obesity has been reported to be an important factor linking bipolar disorder and obesity. Nonetheless, the molecular signature of this connection is perplexing. METHODS:Here, we leverage both meta-analysis and bioinformatics analysis to provide a conspectus and deduce the molecular signature of obesity in bipolar disease patients following psychotropic treatment. Searches were performed on a diverse collection of databases through June 25, 2020. The Newcastle-Ottawa Scale was used to rate the quality of the studies. Analysis of OR, 95% CI, and tests of homogeneity were carried out with STATA software. For the bioinformatics analysis, the LIMMA package which is incorporated into the Gene Expression Omnibus database was used. RESULTS:Our search yielded 138 studies, of which 18 fitted our inclusion criteria. Individuals who are obese have an increased risk of developing bipolar disorder (pooled adjusted OR = 1.32, 95% CI = 1.01-1.62). In a manner analogous to this, the pooled adjusted odds ratio reveals that patients with bipolar disorder have an increased chance of obesity (OR = 1.68, 95% CI = 1.35-2). To deduce the molecular signature of obesity in bipolar disorder patients following psychotropic treatment, three data sets from the Gene Expression Omnibus database (GSE5392, GSE87610, and GSE35977) were integrated and the genes obtained were validated by a cohort of known single nucleotide polymorphism of obesity via direct overlap. Results indicate genes that are activated after psychotropic treatment. Some of these genes are CYBB, C3, OLR1, CX3CR1, C3AR1, CD53, AIF1, LY86, BDNF, ALOX5AP, CXCL10, and the preponderance falls under mesodermal and PI3K-Akt signaling pathway. The ROC analysis reveals a strong discriminating value between the two groups (UBAP2L AUC = 0.806, p = 1.1e-04, NOVA2 AUC = 0.73, p = 6.7e-03). CONCLUSION:Our study shows unequivocal evidence of a bi-directional association between bipolar disorder and obesity, but more crucially, it provides a snapshot of the molecular signature of obesity in bipolar patients as a result of psychotropic medication.
10.1038/s41366-023-01277-6
The prevalence and associated clinical correlates of hyperuricemia in patients with bipolar disorder.
Frontiers in neuroscience
Objective:The prevalence and clinically associated factors of hyperuricemia (HUA) have been widely studied in the general population but rarely in patients with bipolar disorder (BPD) co-morbid with HUA. This study attempted to investigate the prevalence of HUA in BPD patients and analyze the associated correlates of HUA. Materials and methods:In this study, 182 outpatients with BPD and 182 healthy controls participated. The demographic and clinical information were collected. The body weight, height, waist circumference (WC), hip circumference (HC), and blood pressure (BP) were measured. The levels of serum uric acid (UA), triglyceride (TG), high-density lipoprotein (HDL-C), and fasting blood glucose (FBG) were also determined. Results:BPD patients had a significantly higher prevalence of HUA (40.7%) compared to healthy controls (30.2%) (χ = 4.335, = 0.037). The systolic blood pressure (SBP), pulse pressure (PP), FBG, UA, and body mass index (BMI) were higher in the BPD group compared with those in the control group, while the diastolic blood pressure (DBP) and HDL-C level were lower ( < 0.05) in BPD patients. The prevalence of HUA was higher in BPD patients who used antipsychotics combined with mood stabilizers than that in BPD subjects receiving the mood stabilizers alone ( < 0.001). The prevalence of HUA and increased serum UA levels were higher in the manic group (62.1%) than in the depressive (34.3%) or euthymia group (17.0%) ( < 0.001). Additionally, the severity of mania was positively correlated with the UA level ( = 0.410, < 0.001). There were significant differences in terms of MetS (29.7% vs. 14.8%), BMI, HC, WC, TG, and HDL-C between the HUA and the non-HUA groups ( < 0.05). The unconditional logistic regression analysis revealed that high BMI (OR = 1.210; 95%CI: 1.100-1.331) and high TG level (OR = 1.652; 95%CI: 1.058-2.580) were the major risk factorids for HUA in BPD patients. Conclusion:Our study suggests that patients with BPD are prone to metabolic diseases such as HUA. Higher serum levels of TG and high BMI could be associated with HUA development. Clinicians need to regularly monitor and evaluate BPD patients for their serum UA levels, especially for BPD patients with manic/hypomanic episodes and/or under the treatment of antipsychotics combined with mood stabilizers.
10.3389/fnins.2022.998747
The biology of aggressive behavior in bipolar disorder: A systematic review.
Fico Giovanna,Anmella Gerard,Pacchiarotti Isabella,Verdolini Norma,Sagué-Vilavella Maria,Corponi Filippo,Manchia Mirko,Vieta Eduard,Murru Andrea
Neuroscience and biobehavioral reviews
Aggressive behavior (AB) represents a public health concern often associated with severe psychiatric disorders. Although most psychiatric patients are not aggressive, untreated psychiatric illness, including bipolar disorder (BD), may associate with an increased risk of AB. Accurate predictive models of AB are still lacking and it is crucial to delineate AB biomarkers state of the art in BD. We performed a systematic review according to PRISMA guidelines to identify biological correlates of AB in BD. Final results included 20 studies: 10 involving genetic and 10 other biological AB biomarkers (total sample size N = 5,181). Our results pointed to a serotoninergic hypoactivation in violent suicidal BD patients. Similarly, BD violent suicide attempters had a blunted hypothalamic-pituitary-adrenal (HPA) activity. Violent behavior in BD was associated with a chronic inflammatory state. While the role of lipids as biomarkers for AB remains equivocal, uric acid appears as a potential biomarker for hetero-AB in BD. Available data can be useful in the fulfill of specific biomarkers of AB in BD, ultimately leading to the development of accurate predictive models.
10.1016/j.neubiorev.2020.09.015
Serum uric acid levels and different phases of illness in bipolar I patients treated with lithium.
Muti Matteo,Del Grande Claudia,Musetti Laura,Marazziti Donatella,Turri Milo,Cirronis Marco,Pergentini Irene,Corsi Martina,Dell'Osso Liliana,Corsini Giovanni Umberto
Psychiatry research
Recent findings support the role of purinergic system dysfunction in the pathophysiology of bipolar disorder (BD). The present study aimed to evaluate the pattern of serum uric acid levels in a sample of 98 BD I patients followed-up prospectively in a naturalistic study and treated with lithium monotherapy or in association with other mood stabilizers (valproate or carbamazepine), in relation to different phases of illness and to pharmacological treatment. The results showed that uric acid levels were significantly higher in patients suffering from a manic/mixed episode, than in those euthymic or during a depressive phase. Further, these levels were related to the Clinical Global Impression-Bipolar Version (CGI-BP) scale score for the severity of manic symptoms. A positive correlation was found also with male sex and with serum lithium levels. These findings suggest that a dysregulation of the purinergic system may occur during manic/mixed episodes, and they support a possible role of serum uric acid levels as a state-dependent marker of BD manic phases.
10.1016/j.psychres.2014.11.038
Serum uric acid a depression biomarker.
Meng Xiandong,Huang Xia,Deng Wei,Li Jiping,Li Tao
PloS one
OBJECTIVE:We aimed to investigate the difference in serum uric acid(SUA)levels between subtypes of depression and normal population, and whether SUA can be used to identify bipolar disorder depressive episode and major depressive disorder and predict the length of hospital stay. METHODS:1543 depression patients and 1515 healthy controls were obtained according to the entry and exclusion criteria from one mental health center of a tertiary hospital in southwestern China. The diagnosis and classification of depression was in accordance with ICD-10. The SUA value was derived from fasting plasma samples analysis. The level of SUA of all the participants was quantified using Roche cobas8000-c702-MSB automatic biochemical analyzer. Data were analyzed by SPSS18.0 statistical software package. RESULTS:Overall, the level of SUA in patients with depression was lower than that in normal control. Specifically, males' SUA levels were in the interval of [240, 323.3) and [323.3, 406.6), and women were in the [160, 233.3] levels. The SUA level of bipolar disorder depressive episode was higher compared to major depressive disorder level. Interestingly, male patients who were hospitalized for two weeks had higher SUA than those who were hospitalized for three weeks or four weeks. CONCLUSIONS:Our results suggest that the length of hospital stay may be associated with SUA, and when it is difficult to make a differential diagnosis of bipolar disorder depressive episode and major depressive disorder, the level of SUA may be considered. The adjustment of SUA as a method for treating depression needs to be carefully assessed.
10.1371/journal.pone.0229626
Individuals with bipolar disorder have a higher level of uric acid than major depressive disorder: a case-control study.
Lu Zhe,Wang Yingtan,Xun Guanglei
Scientific reports
At present, no well-established biomarkers were ever found to distinguish unipolar depression and bipolar disorder (BD). This study aimed to provide a clearer comparison of UA levels between BD and major depressive disorder. Peripheral UA of 119 patients with BD in acute stage (AS) and 77 in remission stage (RS), and 95 patients with UD in AS and 61 in RS were measured, so were 180 healthy controls. UA levels in BD group were higher than UD and HC groups regardless of the AS or RS, while differences in UA levels between UD group and HC group were not significant. Differences in UA levels of BD-M (bipolar mania/hypomania) were higher than BD-D (bipolar depression) subgroups, and UA levels of BD-M and BD-D subgroups were higher than UD and HC groups. The comparison of number of participants with hyperuricemia among groups confirmed the above results. There were no significant differences in UA levels of between drug-use and drug-free/naïve subgroups. UA could distinguish BD and UD significantly both in acute and remission stage. The study suggests patients with BD had a higher level of UA than UD, especially in mania episode. UA may be a potential biomarker to distinguish BD from UD.
10.1038/s41598-021-97955-4
Uric acid levels in subjects with bipolar disorder: A comparative meta-analysis.
Bartoli Francesco,Crocamo Cristina,Mazza Mario Gennaro,Clerici Massimo,Carrà Giuseppe
Journal of psychiatric research
Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I(2) index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I(2) = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I(2) = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I(2) = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research.
10.1016/j.jpsychires.2016.07.007
Early Life Stress, Brain Development, and Obesity Risk: Is Oxytocin the Missing Link?
Cells
Obesity disease results from a dysfunctional modulation of the energy balance whose master regulator is the central nervous system. The neural circuitries involved in such function complete their maturation during early postnatal periods, when the brain is highly plastic and profoundly influenced by the environment. This phenomenon is considered as an evolutionary strategy, whereby metabolic functions are adjusted to environmental cues, such as food availability and maternal care. In this timeframe, adverse stimuli may program the body metabolism to maximize energy storage abilities to cope with hostile conditions. Consistently, the prevalence of obesity is higher among individuals who experienced early life stress (ELS). Oxytocin, a hypothalamic neurohormone, regulates the energy balance and modulates social, emotional, and eating behaviors, exerting both central and peripheral actions. Oxytocin closely cooperates with leptin in regulating energy homeostasis. Both oxytocin and leptin impact the neurodevelopment during critical periods and are affected by ELS and obesity. In this review article, we report evidence from the literature describing the effect of postnatal ELS (specifically, disorganized/inconstant maternal care) on the vulnerability to obesity with a focus on the role of oxytocin. We emphasize the existing research gaps and highlight promising directions worthy of exploration. Based on the available data, alterations in the oxytocin system may in part mediate the ELS-induced susceptibility to obesity.
10.3390/cells11040623
Treatment of Acquired Hypothalamic Obesity: Now and the Future.
Frontiers in endocrinology
The hypothalamus is the centre of neuroendocrine regulation of energy homeostasis and appetite. Maldevelopment of, or damage to, the key hypothalamic nuclei disrupts the coordinated balance between energy intake and expenditure leading, to rapid and excessive weight gain. Hypothalamic obesity is compounded by a disruption of the hypothalamic-pituitary axis, sleep disruption, visual compromise, and neurological and vascular sequalae. Amongst suprasellar tumors, craniopharyngioma is the most common cause of acquired hypothalamic obesity, either directly or following surgical or radiotherapeutic intervention. At present, therapy is limited to strategies to manage obesity but with a modest and variable impact. Current approaches include optimizing pituitary hormone replacement, calorie restriction, increased energy expenditure through physical activity, behavioral interventions, pharmacotherapy and bariatric surgery. Current pharmacotherapeutic approaches include stimulants that increase energy consumption, anti-diabetic agents, hypothalamic-pituitary substitution therapy, octreotide, and methionine aminopeptidase 2 (MetAP2) inhibitors. Some pharmacological studies of hypothalamic obesity report weight loss or stabilization but reported intervention periods are short, and others report no effect. The impact of bariatric surgery on weight loss in hypothalamic obesity again is variable. Novel or combined approaches to manage hypothalamic obesity are thus required to achieve credible and sustained weight loss. Identifying etiological factors contributing hypothalamic obesity may lead to multi-faceted interventions targeting hyperphagia, insulin resistance, decreased energy expenditure, sleep disturbance, hypopituitarism and psychosocial morbidity. Placebo-controlled trials using current single, or combination therapies are required to determine the impact of therapeutic agents. A well-defined approach to defining the location of hypothalamic damage may support the use of future targeted therapies. Intranasal oxytocin is currently being investigated as an anorexogenic agent. Novel agents including those targeting pro-opimelanocortin-C and AgRP/NPY expressing neurons and the MC4 receptor may result in better outcomes. This article discusses the current challenges in the management of hypothalamic obesity in children and young people and future therapeutic approaches to increasing weight loss and quality of life in these patients.
10.3389/fendo.2022.846880
Oxytocin in metabolic homeostasis: implications for obesity and diabetes management.
Ding C,Leow M K-S,Magkos F
Obesity reviews : an official journal of the International Association for the Study of Obesity
Oxytocin was once understood solely as a neuropeptide with a central role in social bonding, reproduction, parturition, lactation and appetite regulation. Recent evidence indicates that oxytocin enhances glucose uptake and lipid utilization in adipose tissue and skeletal muscle, suggesting that dysfunction of the oxytocin system could underlie the pathogenesis of insulin resistance and dyslipidaemia. Murine studies revealed that deficiencies in oxytocin signalling and oxytocin receptor expression lead to obesity despite normal food intake, motor activity and increased leptin levels. In addition, plasma oxytocin concentration is notably lower in obese individuals with diabetes, which may suggest an involvement of the oxytocin system in the pathogenesis of cardiometabolic disease. More recently, small scale studies demonstrated that intranasal administration of oxytocin was associated with significant weight loss as well as improvements in insulin sensitivity and pancreatic β-cell responsivity in human subjects. The multi-pronged effects of oxytocin signalling on improving peripheral insulin sensitivity, pancreatic function and lipid homeostasis strongly suggest a role for this system as a therapeutic target in obesity and diabetes management. The complexity of obesity aetiology and the pathogenesis of obesity-related metabolic complications underscore the need for a systems approach to better understand the role of oxytocin in metabolic function.
10.1111/obr.12757
Oxytocin as an Anti-obesity Treatment.
Niu JingJing,Tong Jenny,Blevins James E
Frontiers in neuroscience
Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.
10.3389/fnins.2021.743546
Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice.
eLife
Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (Oxt) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. Oxt has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of Oxt signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of or () has little effect on food intake. We herein show that acute conditional KO (cKO) of selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of Oxt rescues the hyperphagic phenotype of the PVH cKO model. Furthermore, we show that cKO of selectively in the posterior hypothalamic regions, especially the arcuate hypothalamic nucleus, a primary center for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data reveal that Oxt signaling in the arcuate nucleus suppresses excessive food intake.
10.7554/eLife.75718
A distinct hypothalamus-to-β cell circuit modulates insulin secretion.
Cell metabolism
The central nervous system has long been thought to regulate insulin secretion, an essential process in the maintenance of blood glucose levels. However, the anatomical and functional connections between the brain and insulin-producing pancreatic β cells remain undefined. Here, we describe a functional transneuronal circuit connecting the hypothalamus to β cells in mice. This circuit originates from a subpopulation of oxytocin neurons in the paraventricular hypothalamic nucleus (PVN), and it reaches the islets of the endocrine pancreas via the sympathetic autonomic branch to innervate β cells. Stimulation of PVN neurons rapidly suppresses insulin secretion and causes hyperglycemia. Conversely, silencing of these neurons elevates insulin levels by dysregulating neuronal signaling and secretory pathways in β cells and induces hypoglycemia. PVN neuronal activity is triggered by glucoprivation. Our findings reveal that a subset of PVN neurons form functional multisynaptic circuits with β cells in mice to regulate insulin secretion, and their function is necessary for the β cell response to hypoglycemia.
10.1016/j.cmet.2021.12.020
Agreement of bioelectrical impedance with dual-energy X-ray absorptiometry and MRI to estimate changes in body fat, skeletal muscle and visceral fat during a 12-month weight loss intervention.
Pietiläinen Kirsi H,Kaye Sanna,Karmi Anna,Suojanen Laura,Rissanen Aila,Virtanen Kirsi A
The British journal of nutrition
The aim of the present study was to analyse the agreement of bioelectrical impedance analysis (BIA) compared with dual-energy X-ray absorptiometry (DXA) and MRI in estimating body fat, skeletal muscle and visceral fat during a 12-month weight loss intervention. A total of nineteen obese adults (twelve females, seven males) aged 20·2-48·6 years, mean BMI 34·6 (SE 0·6) kg/m², participated in the study. Body fat, skeletal muscle and visceral fat index were measured by BIA (Omron BF-500; Omron Medizintechnik) and compared with DXA (body fat and skeletal muscle) at baseline, 5 and 12 months, and with MRI (visceral fat) at baseline and 5 months. The subjects lost 8·9 (SE 1·8) kg (9·0 (SE 1·7) %) of body weight during the 12-month intervention. BIA, as compared to DXA, accurately assessed loss of fat (7·0 (SE 1·5) v. 7·0 (SE 1·4) kg, P= 0·94) and muscle (1·0 (SE 0·2) v. 1·4 (SE 0·3) kg, P= 0·18). While body fat was similar by the two methods, skeletal muscle was underestimated by 1-2 kg using BIA at each time point. Compared to MRI, BIA overestimated visceral fat, especially in males. BIA and DXA showed high correlations for kg fat, both cross-sectionally and longitudinally (r 0·91-0·99). BIA, compared with DXA and MRI, detected kg muscle and visceral fat more accurately cross-sectionally (r 0·77-0·87 and r 0·40-0·78, respectively) than their changes longitudinally (r 0·24-0·61 and r 0·46, respectively). BIA is at its best when assessing the amount or changes in fat mass. It is a useful method for measuring skeletal muscle, but limited in its ability to measure visceral fat.
10.1017/S0007114512003698
Effects of weight loss intervention on body composition and blood pressure among overweight and obese women: findings from the MyBFF@home study.
BMC women's health
BACKGROUND:Obesity is related to the increased incidence of hypertension and in healthy individuals, blood pressure changes with age and body mass. The aims of this paper were to evaluate the effectiveness of the weight loss intervention on body composition and blood pressure, and to evaluate the relationship between these factors among housewives in the MyBFF@home study. METHODS:MyBFF@home intervention was a quasi-experimental study which involved 328 overweight and obese housewives aged 18-59 years old (Control group: 159, Intervention group: 169). Data of the control and intervention group (pre and post intervention who completed the body composition and blood pressure measurements were analysed. Body compositions were measured using the Body Impedance Analyser (InBody 720) and blood pressure (Systolic and Diastolic) was taken using the blood pressure monitoring device (Omron HEM 907) at baseline, 6 month and 12 month. Data analyses (Pearson's correlation test and ANOVA) were performed and analysed using SPSS Statistics for Windows, version 22.0. RESULTS:Visceral fat area, fat mass and body fat percentage, were all significantly decreased in the intervention group compared to the control group after 6 month intervention (p < 0.05). Systolic blood pressure was reduced significantly by - 6.81 mmHg (95% CI: -9.72,-3.90; p < 0.01) in the intervention and by - 7.95 mmHg (95% CI: -11.69,-4.20; p < 0.01) in the control group after 6 month intervention. Diastolic blood pressure was significantly correlated with BMI (r = 0.19), waist circumference (r = 0.23), body fat mass (r = 0.22), body fat percentage (r = 0.18) visceral fat area (r = 0.22) and skeletal muscle mass (r = 0.14) with p < 0.05. At 12-month follow-up, no significant changes of blood pressure were detected in both groups. CONCLUSION:There were significant changes in the body fat and systolic blood pressure over 6 month among the participants in the intervention group compared to the control group. However, both groups were unable to sustain the positive changes in the body fats during the maintenance phase. There was a relationship between the body composition and blood pressure during the weight loss intervention and weight loss maintenance phase. Participation among obese housewives in a community-based intervention programme led to the improvements in blood pressure and body composition.
10.1186/s12905-018-0592-2
Associations between diurnal cortisol patterns and lifestyle factors, psychotic symptoms, and neurological deficits: A longitudinal study on patients with chronic schizophrenia.
Ho Rainbow T H,Fong Ted C T,Wan Adrian H Y,Au-Yeung Friendly S W,Chen Eric Y H,Spiegel David
Journal of psychiatric research
The present study examined the relationships between diurnal cortisol patterns and perceived stress, lifestyle factors, psychotic symptoms, neurological deficits, and daily functioning in patients with chronic schizophrenia. The participants were 149 Chinese patients with chronic schizophrenia, who provided salivary cortisol measures upon waking, before lunchtime, and before bedtime at baseline (Time 1). Self-report measures on perceived stress and lifestyle factors such as body-mass index and daily exercise span were recorded at Time 1. Diagnostic assessments on psychotic symptoms, neurological deficits, and daily functioning were made at Time 1 and Time 2 (3 months later). Latent growth modeling and path modeling analysis were performed to investigate the diurnal cortisol patterns and the relationships with the study variables, respectively. Greater perceived stress and body-mass index and less physical activity were significantly linked to reduced cortisol decline. Reduced cortisol decline at Time 1 significantly predicted greater psychotic (positive and negative) symptoms and more severe neurological deficits in motor coordination and sequencing of complex motor acts at Time 2. The present results contribute to a better understanding of the diurnal cortisol patterns among chronic schizophrenia patients and the associations with lifestyle factors, psychotic symptoms, and neurological deficits. The findings lend support to the neural diathesis-stress model and suggest that hypothalamic-pituitary-adrenal axis may potentially mediate the effects of lifestyle factors on psychotic symptoms and neurological deficits.
10.1016/j.jpsychires.2016.06.014
HDL-apoA-I kinetics in response to 16 wk of exercise training in men with nonalcoholic fatty liver disease.
Whyte Martin B,Shojaee-Moradie Fariba,Sharaf Sharaf E,Cuthbertson Daniel J,Kemp Graham J,Barrett Mark,Jackson Nicola C,Herring Roselle A,Wright John,Thomas E Louise,Bell Jimmy,Umpleby A Margot
American journal of physiology. Endocrinology and metabolism
Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise ( = 15), or conventional lifestyle advice ( = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[C]-leucine and 1,1,2,3,3-H glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL-TAG.
10.1152/ajpendo.00019.2020
Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.
Isgren Anniella,Jakobsson Joel,Pålsson Erik,Ekman Carl Johan,Johansson Anette G M,Sellgren Carl,Blennow Kaj,Zetterberg Henrik,Landén Mikael
Brain, behavior, and immunity
Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication.
10.1016/j.bbi.2014.10.001
Increased risk of hyperlipidemia in patients with bipolar disorder: a population-based study.
Hsu Jer-Hwa,Chien I-Chia,Lin Ching-Heng
General hospital psychiatry
OBJECTIVE:We conducted this nationwide study to examine the epidemiology of hyperlipidemia among Taiwanese patients with bipolar disorder. METHODS:We used a random sample of 766,427 subjects who were ≥18 years old in 2005. Subjects with at least one primary diagnosis of bipolar disorder were identified. Individuals with a primary or secondary diagnosis of hyperlipidemia or medication treatment for hyperlipidemia were also identified. We compared the prevalence of hyperlipidemia in patients with bipolar disorder with the general population in 2005. Furthermore, we investigated this cohort from 2006 to 2010 to detect the incident cases of hyperlipidemia. RESULTS:The prevalence of hyperlipidemia in patients with bipolar disorder was higher than that of the general population [13.5% vs. 7.9%; odds ratio, 1.75; 95% confidence interval (CI), 1.52-2.02] in 2005. The average annual incidence of hyperlipidemia in patients with bipolar disorder was also higher than that of the general population (4.37% vs. 2.55%; risk ratio, 1.66; 95% CI, 1.47-1.87) from 2006 to 2010. CONCLUSIONS:Patients with bipolar disorder had a higher prevalence and incidence of hyperlipidemia compared with the general population. Patients with bipolar disorder coexisting hypertension exhibited a higher likelihood of hyperlipidemia.
10.1016/j.genhosppsych.2015.04.003
Complex polypharmacy in bipolar disorder: Results from a real-world inpatient psychiatric unit.
Psychiatry research
BACKGROUND:Multiple medications are frequently prescribed to patients with bipolar disorder (BD). The aim of the present study was to identify sociodemographic and clinical characteristics associated with complex polypharmacy in patients affected by BD. METHODS:556 patients with BD were included. A semi-structured interview was used to collect sociodemographic and clinical characteristics, as well as pharmacological treatment. Participants were divided in two groups, abased on the use of complex polypharmacy (i.e., a combination of 4 or more psychotropic medications). Differences between the two groups were evaluated with t-test and chi-squared test. A stepwise logistic regression was then applied to identify factors significantly associated with complex polypharmacy. RESULTS:Patients with BD and complex polypharmacy were more likely to be single and unemployed. Moreover, earlier age at onset, longer duration of illness, higher number of hospitalizations, higher prevalence of medical and psychiatric comorbidity, and the use of illicit substances (except heroin) were associated with complex polypharmacy. In the logistic regression model, single status, older age, number of hospitalizations, and the presence of psychiatric comorbidities were regarded as factors significantly associated with complex polypharmacy. CONCLUSIONS:Our findings reflect the need to develop clear guidelines for the long-term management of BD, especially when pharmacological discontinuation is needed.
10.1016/j.psychres.2022.114927
Association between thyroid hormones and comorbid psychotic symptoms in patients with first-episode and drug-naïve major depressive disorder.
Psychiatry research
Thyroid dysfunction is common in major depressive disorder (MDD) patients; however, its relationship with psychotic depression (PD) remains unclear. We aimed to assess thyroid hormones in 1718 first episode drug naïve (FEND) MDD patients and to determine their association with PD. The positive subscale of the Positive and Negative Symptom Scale (PANSS-P), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD) were used to detect clinical symptoms. The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), and thyroid peroxidases antibody (TPOAb) were assessed. The logistic regression model was conducted to determine risk factors for PD, and the Area Under the Curve (AUC) was used to test the performance of this model. 171 (10%) patients were identified as having PD. Serum levels of TSH, TgAb, and TPOAb displayed small-to-moderate associations with PANSS-P. HAMA score, HAMD score, and TSH levels were independently associated with PD. The regression model had excellent power to distinguish PD patients from non-PD patients with an AUC value of 0.93. Our study suggests TSH levels and severity of depression and anxiety symptoms were independent risk factors for PD. Regular thyroid function tests may help early detect PD.
10.1016/j.psychres.2023.115052
Prevalence and clinical-demographic correlates of hyperhomocysteinemia in inpatients with bipolar disorder in a Han Chinese population.
Zhou Shuang-Jiang,Zhang Li-Gang,Chen Hong-Mei,Li Ju-Yan,Li Ran,Zhang Xi-Mei,Wang Ning,Soares Jair C,Cassidy Ryan M,Zheng Yingjun,Ning Yuping,Wang Shao-Li,Chen Jing-Xu,Zhang Xiang-Yang
Psychiatry research
Recent studies have reported that hyperhomocystinemia (HHcy) is highly prevalent in patients with bipolar disorder (BD), placing them at greater risk of cardiovascular disease and possibly serving as a disease biomarker. However, the correlation of HHcy with demographic or clinical parameters is not well known. In this study, we examined the prevalence of HHcy and its association with these parameters in a sample of Chinese BD patients. Fasting plasma homocysteine (Hcy) levels were determined in 198 BD inpatients and 84 healthy controls. HHcy was defined when Hcy concentration exceeded 15.0µmol/L. Affective symptomatology was assessed by the Young Mania Rating Scale, Hamilton Depression Rating Scale and the Clinical Global Impressions severity scale. Compared to healthy controls, BD patients had a significantly higher prevalence (34.85% vs. 19.05%) of HHcy and a higher absolute level of homocysteine. Logistic regression analysis demonstrated that BD patients with HHcy were more likely to be male, have elevated BMI, more frequent treatment on lithium but less on valproate. These results suggest that Chinese inpatients with bipolar disorder have a higher rate of HHcy than the general population, and those at greatest risk are male, have an elevated BMI, and take more lithium but less valproate therapy.
10.1016/j.psychres.2017.08.063
10-year CVD risk in Han Chinese mainland patients with schizophrenia.
Zhao Shuai,Xia HaiLong,Mu JingJing,Wang Long,Zhu Li,Wang AnZhen,Zhou XiaoQin
Psychiatry research
People with schizophrenia have a shortened life expectancy, with cardiovascular disease (CVD) being the primary contributor to this excessive mortality. A total of 466 inpatients with schizophrenia and 507 healthy community controls in the Chinese mainland were recruited in this study. Sociodemographic information, medical history, and smoking history were recorded. In addition, total cholesterol (TC), fasting blood glucose (FBG), triglycerides (TG), and high-destiny lipoprotein cholesterol (HDL-C) were analyzed. The 10-year CVD risk was significantly higher in patients with schizophrenia compared with healthy controls. Male schizophrenia patients had significantly higher Framingham risk scores (FRS) than the females. Patients with schizophrenia carried significantly greater risk factors of CVD; body-mass index (BMI), TG and smoking prevalence were significantly higher than in the health community controls, while FBG and HDL-C were on the contrary. Smoking was significantly associated with FRS among schizophrenia inpatients. Collectively, these results suggest that Han Chinese mainland patients with schizophrenia harbor a high 10-year CVD risk when compared with healthy controls, especially in males. CVD in schizophrenia patients requires greater attention by clinicians and researchers.
10.1016/j.psychres.2018.04.020
Homocysteine levels and glucose metabolism in non-obese, non-diabetic chronic schizophrenia.
Henderson D C,Copeland P M,Nguyen D D,Borba C P,Cather C,Eden Evins A,Freudenreich O,Baer L,Goff D C
Acta psychiatrica Scandinavica
OBJECTIVE:We studied a sample of schizophrenia out-patients to test the hypotheses that serum homocysteine concentrations would correlate positively with measures of glucose metabolism. METHOD:Subjects underwent a nutritional assessment and fasting plasma, serum insulin and homocysteine tests. RESULTS:Males had a significantly higher homocysteine levels than females (7.69 +/- 1.42 microM vs. 6.63 +/- 1.40 microM; P = 0.02). Comparing subjects with normal fasting glucose (NFG) (glucose < 100 mg/dl) and impaired fasting glucose (IFG) (> or = 100 mg/dl) subjects with IFG (mean 8.2 +/- 1.5 microM) had significantly higher homocysteine levels than those with NFG (mean 7.2 +/- 1.4 microM, P = 0.03). IFG was also associated with greater mean values for a Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.002) and diastolic blood pressure (P = 0.045). CONCLUSION:The group with IFG had higher fasting serum homocysteine concentrations than those with NFG which supports a connection to an important cardiovascular risk factor.
10.1111/j.1600-0447.2005.00621.x
Dissecting Causal Associations of Diet-Derived Circulating Antioxidants with Six Major Mental Disorders: A Mendelian Randomization Study.
Antioxidants (Basel, Switzerland)
Although observational studies have suggested associations between circulating antioxidants and many mental disorders, causal inferences have not been confirmed. Mendelian randomization (MR) analyses were conducted using summary-level statistics from genome-wide association studies (GWASs) to explore whether genetically determined absolute circulating antioxidants (i.e., ascorbate, retinol, β-carotene, and lycopene) and metabolites (i.e., α- and γ-tocopherol, ascorbate, and retinol) were causally associated with the risk of six major mental disorders, including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BIP), schizophrenia (SCZ), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). MR analyses were performed per specific-outcome databases, including the largest GWAS published to date (from 9725 for OCD to 413,466 for BIP participants), UK Biobank (over 370,000 participants), and FinnGen (over 270,000 participants), followed by meta-analyses. We found no significant evidence that genetically determined diet-derived circulating antioxidants were significantly causally associated with the risk of the six above-mentioned major mental disorders. For absolute antioxidant levels, the odds ratios (ORs) ranged from 0.91 (95% CI, 0.67-1.23) for the effect of β-carotene on OCD to 1.18 (95% CI, 0.90-1.54) for the effect of ascorbate on OCD. Similarly, for antioxidant metabolites, ORs ranged from 0.87 (95% CI, 0.55-1.38) for the effect of ascorbate on MDD to 1.08 (95% CI, 0.88-1.33) for the effect of ascorbate on OCD. Our study does not support significant causal associations of genetically determined diet-derived circulating antioxidants with the risk of major mental disorders.
10.3390/antiox12010162
Assessing dietary and lifestyle risk factors and their associations with disease comorbidities among patients with schizophrenia: A case-control study from Bahrain.
Jahrami Haitham Ali,Faris Mo'ez Al-Islam Ezzat,Saif Zahraa Qassim,Hammad Laila Habib
Asian journal of psychiatry
OBJECTIVE:Acquired dietary habits and lifestyle behaviors of patients with schizophrenia may affect their life expectancy, disease complications and prognosis. The objectives of the current study were to assess the dietary habits and other lifestyle behaviors for Bahraini patients with schizophrenia, and to determine their associations with different medical comorbidities. METHOD:A case-control study was conducted during the period of March to December 2016. A sample of 120 cases were recruited from the Psychiatric Hospital, Bahrain and age-sex-matched with 120 controls. Controls were recruited from primary health centres, and were free from serious mental illness. Dietary habits and lifestyle behaviors including smoking, alcohol intake and physical activity were assessed using a questionnaire. All medical records were reviewed retrospectively. Logistic regression analysis was used to identify dietary and lifestyle risk factors that are associated with one or more disease comorbidities. RESULTS:Cases had higher prevalence of smoking and alcohol intake, excessive dietary intake, and decreased physical activity (all P<0.05) compared with controls. Cases appeared to be at higher risk for developing chronic medical conditions such as obesity, type 2 diabetes, hypertension, cardiovascular disease, and musculoskeletal disorders. Cases were three times more likely to have up to three or more medical comorbidities compared with controls. Excessive dietary intake and decreased physical activity were identified as the main risk factors. CONCLUSION:Excessive caloric intake and decreased physical activity represent the main dietary and lifestyle risk factors associated with comorbidities among patients with schizophrenia in Bahrain.
10.1016/j.ajp.2017.03.036
Increased Dietary Inflammatory Index Is Associated with Schizophrenia: Results of a Case-Control Study from Bahrain.
Jahrami Haitham,Faris Mo'ez Al-Islam,Ghazzawi Hadeel Ali,Saif Zahra,Habib Layla,Shivappa Nitin,Hébert James R
Nutrients
BACKGROUND:Several studies have indicated that chronic low-grade inflammation is associated with the development of schizophrenia. Given the role of diet in modulating inflammatory markers, excessive caloric intake and increased consumption of pro-inflammatory components such as calorie-dense, nutrient-sparse foods may contribute toward increased rates of schizophrenia. This study aimed to examine the association between dietary inflammation, as measured by the dietary inflammatory index (DII), and schizophrenia. METHODS:A total of 120 cases attending the out-patient department in the Psychiatric Hospital/Bahrain were recruited, along with 120 healthy controls matched on age and sex. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a comprehensive food frequency questionnaire (FFQ). Logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders including age, sex, body mass index, education, employment, diabetes, hypertension, and cardiovascular disease with E-DII expressed both as a continuous variable and categorized as quartiles. RESULTS:The mean E-DII score for the entire sample was 1.79 ± 1.52, indicating a generally pro-inflammatory diet. The cases with schizophrenia appeared to have a higher E-DII score compared to controls: 1.99 ± 1.39 vs. 1.60 ± 1.38, respectively ( = 0.009). For every one unit increase in the E-DII score, the odds of having schizophrenia increased by 62% (OR 1.62; 95% CI 1.17-2.26). Similarly, increased risk was observed when the E-DII was used as quartiles, with participants in most pro-inflammatory quartile 4 being nearly 6 times more likely to be schizophrenic than participants in the most anti-inflammatory group quartile 1 (OR 5.96; 1.74-20.38; -trend = 0.01). CONCLUSIONS:The data suggest that a pro-inflammatory diet, as indicated by increasing E-DII score, is associated with schizophrenia. This is the first study to examine the association between the DII and schizophrenia in a Middle Eastern population. Although these results are consistent with findings from research conducted in depression, additional studies are required before generalizing the findings to other populations.
10.3390/nu11081867
Usefulness of the Mini Nutritional Assessment (MNA) in predicting the nutritional status of people with mental disorders in Taiwan.
Tsai Alan C,Chou Yuan-Ti,Chang Tsui-Lan
Journal of clinical nursing
OBJECTIVE:The study was to evaluate the ability of the Mini Nutritional Assessment in predicting malnutrition in people with three subtypes of mental disorder (schizophrenia, major depression and bipolar disorder) in Taiwan. DESIGN:The study involved a convenience sample of 120 residents of psychiatric wards managed by a hospital in central Taiwan (52 with schizophrenia, 36 with major depression and 32 with bipolar disorder) classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. METHODS:A structured questionnaire elicited subjects' personal data, disease history and answers to questions in the Mini Nutritional Assessment. Serum and anthropometrical parameters were measured. Nutritional status was evaluated with a content-equivalent version of the Mini Nutritional Assessment (Taiwan version-1, T1). RESULTS:The Mini Nutritional Assessment-Taiwan version-1 was effective in assessing the nutritional status of people of all three subtypes of disorder. Nutritional statuses predicted with the Mini Nutritional Assessment-Taiwan version-1 agreed well with other nutritional indicators such as BMI, waist circumference and appetite status. According to the Mini Nutritional Assessment-Taiwan version-1, people with major depression were more likely to be at risk of undernutrition, whereas people with schizophrenia or bipolar disorder were more likely to be at risk of overnutrition. CONCLUSION:The Mini Nutritional Assessment-Taiwan version-1 can effectively grade both undernutrition and overnutrition of people with schizophrenia, major depression or bipolar disorder. RELEVANCE TO CLINICAL PRACTICE:The Mini Nutritional Assessment enables nurses to monitor emerging nutritional problems in people with psychiatric disorder without relying on subjective judgement. With proper intervention, it can help reduce nutrition-related chronic conditions in these individuals and save on healthcare cost.
10.1111/j.1365-2702.2010.03467.x
Associations of polycyclic aromatic hydrocarbons, water-soluble ions and metals in PM with liver function: Evidence from schizophrenia cohort.
The Science of the total environment
BACKGROUND:Fine particulate matter (PM) was reported to impact liver function, but the roles of specific PM chemical components remained to be explored. Besides, severe liver dysfunction in schizophrenia patients deserves attention. OBJECTIVE:To investigate the associations of short-term PM components with liver function in schizophrenia patients. METHODS:A repeated-measures study based on schizophrenia cohort including 1023 visits (n = 446) was conducted during 2017-2020. Liver function was reflected by 10 indicators including liver enzymes, proteins and bilirubin et al. Monitoring data of PM and its components, including 16 polycyclic aromatic hydrocarbons (PAHs), 4 water-soluble ions and 10 metals were collected. Linear mixed effect and Bayesian kernel machine regression (BKMR) models were used to evaluate the single and combined effects of PM components (0-3 day) on liver function in schizophrenia patients. RESULTS:Several PAHs were significantly associated with liver enzymes, while water-soluble ions and metal components had almost no association. Specifically, with per interquartile range (IQR) increased in Fluoranthene, levels of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) increased by 2.06 %, 5.07 %, 4.94 % and 5.56 %, respectively. An IQR increases in Benzo[a]pyrene was significantly associated with 6.62 %, 3.67 % and 7.83 % increase in ALT, AST and GGT. Almost all PAHs, sulfate, nitrate, ammonium, Sb, Al, As, Pb, Mn and Tl were positively associated with albumin (ALB). Phenanthrene was associated with increased levels of direct bilirubin (DBIL) and total bilirubin (TBIL). The combined effects of significant PM components on ALP, GGT, ALB, globulin (GLOB), ratio of albumin to globulin (A/G), TBIL and total bile acid (TBA) were found by BKMR, respectively. CONCLUSIONS:Findings highlight the short-term combined effects of PM components, especially PAHs, on liver function in schizophrenia patients, which contribute to the management of PM sources including combustion activities and traffic emissions as well as improving schizophrenia comorbidities.
10.1016/j.scitotenv.2023.161624
Sunshine duration and risks of schizophrenia hospitalizations in main urban area: Do built environments modify the association?
The Science of the total environment
BACKGROUND:Although studies have explored the relationship between sunshine duration and schizophrenia, the evidence was ambiguous. Different built environments may alter the effect of sunlight on schizophrenia, thus the purpose of this study was to investigate the effects of built environments on the sunshine duration-schizophrenia association. MATERIALS AND METHODS:Daily schizophrenia hospitalizations data during 2017-2020 in Hefei's main urban area, China, and corresponding meteorological factors as well as ambient pollutants were collected. The impact of sunshine duration on schizophrenia admissions in urban areas was investigated using a generalized additive model combined with a distributed lagged nonlinear model. Additionally, the various modifying effects of different Building Density, Building Height, Normalized Vegetation Index, and Nighttime Light were also explored between sunshine duration and schizophrenia. RESULTS:We observed that inadequate sunshine duration (<5.3 h) was associated with an increase in schizophrenia hospital admissions, with a maximum relative risk of 1.382 (95 % confidence interval (CI): 1.069-1.786) at 2.9 h. In turn, adequate sunshine duration reduced the risk of schizophrenia hospitalizations. Subgroup analyses indicated females and old patients were particularly vulnerable. In the case of insufficient sunshine duration, significant positive effects were noticed on schizophrenia risk at High-Building Density and High-Nighttime Light. Higher NDVI as well as Building Height were found to be associated with lower risks of schizophrenia. CONCLUSIONS:Given that sunshine duration in various built environments might lead to distinct effects on schizophrenia hospitalizations. Our findings assist in identifying vulnerable populations that reside in particular areas, thus suggesting policymakers provide advice to mitigate the onset of schizophrenia by allocating healthcare resources rationally and avoiding adverse exposures to vulnerable populations timely.
10.1016/j.scitotenv.2023.162057
Prevalence of non-alcoholic fatty liver disease in pediatric mental disorder inpatients: a tertiary mental health referral hospital study.
Revista espanola de enfermedades digestivas
BACKGROUND AND AIM:Studies have revealed a high prevalence of non-alcoholic fatty liver disease (NAFLD) among adult patients with mental disorders, as well as its associate risk factors, however little is known about these in pediatric population. The aim of the present study is to investigate the prevalence of NAFLD in pediatric inpatients with mental disorder, as well as to explore the risk factors. METHODS:In this retrospective study, we included 1156 pediatric inpatients with mental disorder admitted to our hospital between January 2020 and December 2021, including inpatients with schizophrenia, bipolar disorder, depressive disorder and other mental disorders. Relevant clinical data were obtained from the electronic medical records. We calculated the prevalence rate of NAFLD, and compared NAFLD prevalence between gender, mental disorders types, antipsychotics use, and comorbidities. Multivariable logistic regression was used to examine risk factors associated with NAFLD. RESULTS:The prevalence of NAFLD in pediatric inpatients with mental disorders was 7.35% (85/1156). Patients with NAFLD had senior age than those without NAFLD (15.33±1.75 vs 14.21±1.95 year-old, P<0.001). The NAFLD prevalence in participants with schizophrenia (12.11%) was higher than in participants with bipolar disorder (8.45%), depressive disorder (7.06%) and other mental disorders (2.97%)(p=0.002). The NAFLD prevalence was higher in participants who used antipsychotics (8.70%) than those who didn't (5.45%) (p=0.038). Multivariate analysis revealed that senior age, body weight (overweight/obese) and dyslipidemia were independent risk factors for NAFLD in pediatric inpatients with mental disorders. CONCLUSIONS:The NAFLD prevalence was is higher in those patients with schizophrenia and receiving antipsychotic medication. Metabolic factors and longer evolution may explain these differences.
10.17235/reed.2022.8986/2022
Atypical antipsychotics-induced metabolic syndrome and nonalcoholic fatty liver disease: a critical review.
Xu Haiyun,Zhuang Xiaoyin
Neuropsychiatric disease and treatment
The atypical antipsychotics (AAPs) have been used as first-line drugs in psychiatric practice for a wide range of psychotic disorders, including schizophrenia and bipolar mania. While effectively exerting therapeutic effects on positive and negative symptoms, as well as cognitive impairments in schizophrenia patients, these drugs are less likely to induce extrapyramidal symptoms compared to typical antipsychotics. However, the increasing application of them has raised questions on their tolerability and adverse effects over the endocrine, metabolic, and cardiovascular axes. Specifically, AAPs are associated to different extents, with weight gain, metabolic syndrome (MetS), and nonalcoholic fatty liver disease (NAFLD). This article summarized clinical evidence showing the metabolic side effects of AAPs in patients with schizophrenia, and experimental evidence of AAPs-induced metabolic side effects observed in animals and cell culture studies. In addition, it discussed potential mechanisms involved in the APPs-induced MetS and NAFLD.
10.2147/NDT.S208061
Obesity in patients with bipolar disorder: a biopsychosocial-behavioral model.
Wildes Jennifer E,Marcus Marsha D,Fagiolini Andrea
The Journal of clinical psychiatry
OBJECTIVE:We provide a model to explicate how factors representing different levels of analysis (i.e., biology, psychology, sociodemographics, and behavior) interact to influence the onset and maintenance of obesity in bipolar disorder. DATA SOURCES:We conducted MEDLINE (1966-2005) and PsycInfo (1872-2005) searches of all English-language articles using the keywords obesity, body weight, weight gain, and metabolic syndrome combined with bipolar disorder, depression, atypical depression, binge eating, and pharmacotherapy. STUDY SELECTION:Studies were selected if they provided data regarding (1) the prevalence of obesity in patients with bipolar disorder, (2) correlates of obesity in patients with bipolar disorder, or (3) evidence that a clinical feature(s) or correlate(s) of bipolar disorder is associated with obesity. Ninety-two studies were reviewed. DATA SYNTHESIS:Obesity is prevalent in patients with bipolar disorder and is associated with increased medical morbidity and poorer psychiatric outcome. Variables that may interact to influence the onset and maintenance of obesity in bipolar disorder include genetic factors, neurotransmitter abnormalities, atypical depression, eating behaviors, pharmacotherapy, age, gender, socioeconomic status, and physical inactivity. CONCLUSIONS:Although the exact causes of obesity in bipolar disorder undoubtedly vary across patients, the etiologic cascade, which includes biological, psychological, and sociodemographic variables, ultimately directly or indirectly affects levels of physical activity and eating behavior, leading to obesity in this population. Behavioral interventions aimed at targeting physical inactivity and overeating in bipolar disorder patients are needed, as are better screening and treatment for binge eating. Finally, there is a clear need for ongoing research to explicate the causes and consequences of obesity across levels of analysis.
Impact of Psychotropic Medication Effects on Obesity and the Metabolic Syndrome in People With Serious Mental Illness.
Frontiers in endocrinology
People with serious mental illness (SMI), including schizophrenia, bipolar disorder, and major depressive disorder, have a higher mortality rate and shortened life expectancy. This is mainly attributable to physical diseases, particularly cardiovascular diseases (CVDs). Important risk factors for CVDs are obesity and other metabolic abnormalities, which are especially prevalent in people with SMI. Several factors contribute to this increased risk, including unhealthy lifestyles. Psychotropic medication independently further increases this risk. In this review we want to examine the relationship between obesity and other components of the metabolic syndrome and psychotropic medication in people with SMI.
10.3389/fendo.2020.573479
Obesity in bipolar disorder: an overview.
McElroy Susan L,Keck Paul E
Current psychiatry reports
Bipolar disorder (BD) is associated with obesity, overweight, and abdominal obesity, and BD individuals with obesity have a greater illness burden. Factors related to BD, its treatment, and the individual may all contribute to BD's association with obesity. Management strategies for the obese BD patient include use of medications with better metabolic profiles, lifestyle interventions, and adjunctive pharmacotherapy for weight loss. Obesity-related psychiatric and medical comorbidities should also be assessed and managed. Bariatric surgery may be an option for carefully selected patients. Greater research into the theoretical underpinnings and clinical management of the BD-obesity connection is needed.
10.1007/s11920-012-0313-8
Obesity in Adolescents with Psychiatric Disorders.
Chao Ariana M,Wadden Thomas A,Berkowitz Robert I
Current psychiatry reports
PURPOSE OF REVIEW:This narrative review synthesized recent research related to obesity in adolescents with psychiatric disorders, with a focus on epidemiology, mechanisms, and weight management approaches. The paper reviews literature on depressive and anxiety disorders, bipolar disorder, and schizophrenia spectrum and other psychotic disorders. RECENT FINDINGS:Depression has a bidirectional relationship with obesity. Bipolar disorder and schizophrenia spectrum disorders, and their treatments, increase the risk of developing obesity. Mechanisms underlying this weight gain include lifestyle and environmental factors and psychiatric medications, though emerging evidence has also suggested the role of genetic and neuroendocrine processes. Evidence about the most effective treatments for obesity in adolescents with psychiatric disorders remains limited. Adolescents with psychiatric disorders are at high risk for obesity. Close monitoring for increases in weight and cardiometabolic risk factors with use of antipsychotic and mood-stabilizing medications is recommended. Clinical trials are needed that test the efficacy of weight management strategies for this population.
10.1007/s11920-019-0990-7
Obesity and overweight among children and adolescents with bipolar disorder from the general population: A review of the scientific literature and a meta-analysis.
Girela-Serrano Braulio M,Guerrero-Jiménez Margarita,Spiers Alexander D V,Gutiérrez-Rojas Luis
Early intervention in psychiatry
There is substantial evidence of the high prevalence of obesity (OB) and overweight (OW) and their association with increased medical and psychiatric burden among adults with bipolar disorder (BD). However, little is known regarding its prevalence among young people with BD, other than the risk from psychotropic medication, which has been the focus of research in this population. We present a systematic review and meta-analysis of the literature on prevalence and correlates of OB and OW children and adolescents with BD using a different perspective than impact of medication. Four studies met inclusion criteria. The prevalence of OB in children and adolescents with BD was 15% (95% CI 11-20%). We observed a higher prevalence of OB in comparison to the general population. Different studies found significant associations between OB, OW, and BD in young populations including non-Caucasian race, physical abuse, suicide attempts, self-injurious behaviours, psychotropic medication, and psychiatric hospitalizations.
10.1111/eip.13137
Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms.
Liu Clarissa M,Spaulding Mai O,Rea Jessica J,Noble Emily E,Kanoski Scott E
International journal of molecular sciences
The neuropeptide oxytocin is produced in the paraventricular hypothalamic nucleus and the supraoptic nucleus of the hypothalamus. In addition to its extensively studied influence on social behavior and reproductive function, central oxytocin signaling potently reduces food intake in both humans and animal models and has potential therapeutic use for obesity treatment. In this review, we highlight rodent model research that illuminates various neural, behavioral, and signaling mechanisms through which oxytocin's anorexigenic effects occur. The research supports a framework through which oxytocin reduces food intake via amplification of within-meal physiological satiation signals rather than by altering between-meal interoceptive hunger and satiety states. We also emphasize the distributed neural sites of action for oxytocin's effects on food intake and review evidence supporting the notion that central oxytocin is communicated throughout the brain, at least in part, through humoral-like volume transmission. Finally, we highlight mechanisms through which oxytocin interacts with various energy balance-associated neuropeptide and endocrine systems (e.g., agouti-related peptide, melanin-concentrating hormone, leptin), as well as the behavioral mechanisms through which oxytocin inhibits food intake, including effects on nutrient-specific ingestion, meal size control, food reward-motivated responses, and competing motivations.
10.3390/ijms221910859
Oxytocin and Vasopressin Systems in Obesity and Metabolic Health: Mechanisms and Perspectives.
Ding Cherlyn,Magkos Faidon
Current obesity reports
PURPOSE OF REVIEW:The neurohypophysial endocrine system is identified here as a potential target for therapeutic interventions toward improving obesity-related metabolic dysfunction, given its coinciding pleiotropic effects on psychological, neurological and metabolic systems that are disrupted in obesity. RECENT FINDINGS:Copeptin, the C-terminal portion of the precursor of arginine-vasopressin, is positively associated with body mass index and risk of type 2 diabetes. Plasma oxytocin is decreased in obesity and several other conditions of abnormal glucose homeostasis. Recent data also show non-classical tissues, such as myocytes, hepatocytes and β-cells, exhibit responses to oxytocin and vasopressin receptor binding that may contribute to alterations in metabolic function. The modulation of anorexigenic and orexigenic pathways appears to be the dominant mechanism underlying the effects of oxytocin and vasopressin on body weight regulation; however, there are apparent limitations associated with their use in direct pharmacological applications. A clearer picture of their wider physiological effects is needed before either system can be considered for therapeutic use.
10.1007/s13679-019-00355-z
Oxytocin and potential benefits for obesity treatment.
Olszewski Pawel K,Klockars Anica,Levine Allen S
Current opinion in endocrinology, diabetes, and obesity
PURPOSE OF REVIEW:Laboratory animal experiments have consistently shown that oxytocin causes early termination of food intake, thereby promoting a decrease in body weight in a long term. Recent studies have also assessed some of oxytocin's effects on appetite and energy balance in humans. The present study examines the findings of the key basic research and of the few clinical studies published thus far in the context of potential benefits and challenges stemming from the use of oxytocin in obese patients. RECENT FINDINGS:Basic research indicates the involvement of oxytocin in satiety, processing, in reducing a drive to eat for pleasure and because of psychosocial factors. Although the results of clinical studies are very scarce, they suggest that oxytocin administered intranasally in humans decreases energy-induced and reward-induced eating, supports cognitive control of food choices, and improves glucose homeostasis, and its effectiveness may be BMI dependent. SUMMARY:Despite the wealth of basic research showing broad anorexigenic effects of oxytocin, clinical studies on oxytocin's therapeutic potential in obesity, are still in their infancy. Future implementation of oxytocin-based pharmacological strategies in controlling energy balance will likely depend on our ability to integrate diverse behavioral and metabolic effects of oxytocin in obesity treatment regimens.
10.1097/MED.0000000000000351
Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State.
Li Chia,Navarrete Jovana,Liang-Guallpa Jing,Lu Chunxia,Funderburk Samuel C,Chang Rui B,Liberles Stephen D,Olson David P,Krashes Michael J
Cell metabolism
Understanding the neural framework behind appetite control is fundamental to developing effective therapies to combat the obesity epidemic. The paraventricular hypothalamus (PVH) is critical for appetite regulation, yet, the real-time, physiological response properties of PVH neurons to nutrients are unknown. Using a combination of fiber photometry, electrophysiology, immunohistochemistry, and neural manipulation strategies, we determined the population dynamics of four molecularly delineated PVH subsets implicated in feeding behavior: glucagon-like peptide 1 receptor (PVH), melanocortin-4 receptor (PVH), oxytocin (PVH), and corticotropin-releasing hormone (PVH). We identified both calorie- and state-dependent sustained activity increases and decreases in PVH and PVH populations, respectively, while observing transient bulk changes of PVH, but no response in PVH, neurons to food. Furthermore, we highlight the role of PVH neurons in orchestrating acute feeding behavior, independent of the anti-obesity drug liraglutide, and demonstrate the indispensability of PVH and PVH, but not PVH PVH neurons, in body weight maintenance.
10.1016/j.cmet.2018.10.016
Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance.
Zhang Guo,Bai Hua,Zhang Hai,Dean Camin,Wu Qiang,Li Juxue,Guariglia Sara,Meng Qingyuan,Cai Dongsheng
Neuron
Hypothalamic neuropeptides play essential roles in regulating energy and body weight balance. Energy imbalance and obesity have been linked to hypothalamic signaling defects in regulating neuropeptide genes; however, it is unknown whether dysregulation of neuropeptide exocytosis could be critically involved. This study discovered that synaptotagmin-4, an atypical modulator of synaptic exocytosis, is expressed most abundantly in oxytocin neurons of the hypothalamus. Synaptotagmin-4 negatively regulates oxytocin exocytosis, and dietary obesity is associated with increased vesicle binding of synaptotagmin-4 and thus enhanced negative regulation of oxytocin release. Overexpressing synaptotagmin-4 in hypothalamic oxytocin neurons and centrally antagonizing oxytocin in mice are similarly obesogenic. Synaptotagmin-4 inhibition prevents against dietary obesity by normalizing oxytocin release and energy balance under chronic nutritional excess. In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases.
10.1016/j.neuron.2010.12.036
An oxytocinergic neural pathway that stimulates thermogenic and cardiac sympathetic outflow.
Cell reports
Oxytocin alters autonomic functions besides social behaviors. However, the central neuronal links between hypothalamic oxytocinergic neurons and the autonomic nervous system remain unclear. Here we show that oxytocinergic neurons in the rat paraventricular hypothalamic nucleus (PVH), a pivotal site for energy homeostasis, innervate sympathetic premotor neurons in the rostral medullary raphe region (rMR) to stimulate brown adipose tissue (BAT) thermogenesis and cardiovascular functions. Oxytocin receptor stimulation in the rMR evokes BAT thermogenesis and tachycardia. In vivo optogenetic stimulation of the PVH→rMR long-range oxytocinergic pathway, using a virus-mediated system for amplified gene expression in oxytocinergic neurons, not only elicits BAT thermogenic and cardiac responses but also potentiates sympathetic responses evoked by glutamatergic transmission in the rMR. The PVH→rMR oxytocinergic pathway connects the hypothalamic circuit for energy homeostasis to thermogenic and cardiac sympathetic outflow, and, therefore, its defects may cause obesity and impaired thermoregulation, as seen in Prader-Willi syndrome.
10.1016/j.celrep.2022.111380
Oxytocin neurons enable social transmission of maternal behaviour.
Nature
Maternal care, including by non-biological parents, is important for offspring survival. Oxytocin, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.
10.1038/s41586-021-03814-7
A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis.
General hospital psychiatry
BACKGROUND:Schizophrenia and antipsychotic use are associated with clinically significant weight gain and subsequent increased mortality. Despite weight loss medications (WLMs) licensed by regulatory bodies (FDA, EMA, and MHRA) being available, current psychiatric guidelines recommend off-label alternatives, which differ from non-psychiatric guidelines for obesity. OBJECTIVE:Evaluate the efficacy of licensed WLMs on treating antipsychotic-induced weight gain (AIWG) and obesity in schizophrenia and psychosis (OSP). METHOD:A literature search was conducted using Medline, EMBASE, PsycINFO and Cochrane Library online databases for human studies using licensed WLMs to treat AIWG and OSP. RESULTS:Three RCTs (two liraglutide, one naltrexone-bupropion), one unpublished open-label trial (naltrexone-bupropion), and seven observational studies (five liraglutide, one semaglutide, one multiple WLMs) were identified. Results for liraglutide showed statistically significant improvement in weight, BMI, waist circumference, HbA1c, cholesterol, and LDL readings on meta-analysis. Evidence was mixed for naltrexone-bupropion with no detailed studies conducted for setmelanotide, or stimulants. CONCLUSION:Evidence is strongest for liraglutide compared to other licensed WLMs. The findings, particularly the inclusion of human trial data, provide evidence for liraglutide use in treating AIWG and OSP, which would better align psychiatric practice with non-psychiatric practices around obesity. The findings also identify continued literature gaps regarding other licensed WLMs.
10.1016/j.genhosppsych.2022.07.006
Antipsychotic drugs and obesity.
Correll Christoph U,Lencz Todd,Malhotra Anil K
Trends in molecular medicine
Mechanisms underlying antipsychotic cardiometabolic adverse effects are incompletely understood. This hampers the identification of high-risk patients, low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical, molecular and genetic data suggest that: (i) antipsychotic-naïve samples provide the greatest power for mechanistic studies; (ii) weight and metabolic effects can be discordant, pointing to overlapping and distinct mechanisms; (iii) antipsychotics affect satiety and energy homeostasis signaling; (iv) the specific peptides mediating these effects are unknown but probably overlap with those involved in idiopathic obesity; and (v) single nucleotide polymorphisms in genes encoding known neurotransmitter receptors and metabolic proteins are promising pharmacogenomic targets for countering adverse affects. However, sophisticated molecular studies and genome-wide association studies, ideally in antipsychotic-naïve/first episode samples, are needed to further advance the field.
10.1016/j.molmed.2010.10.010
Potential for oxytocin use in children and adolescents with mental illness.
Netherton Elisabeth,Schatte Dawnelle
Human psychopharmacology
BACKGROUND:Oxytocin, long known for its role in childbirth and breastfeeding, has recently come under investigation for its psychoactive properties. We investigated its potential for use in adolescent psychiatric populations for anxiety, depression, attachment disorders, and conduct disorder. METHODS:We conducted a thorough search of the literature using the Pubmed and Psychinfo databases and reviewed both the Journal of the American Academy of Child and Adolescent Psychiatry from January 2000 until June 2010 and the new research abstracts from the 2009 and 2008 American Academy of Child and Adolescent Psychiatry conferences. We also surveyed the studies, both ongoing and recruiting, currently receiving National Institutes of Health funding to study oxytocin. RESULTS:We found numerous articles outlining benefits of intranasal oxytocin administration on individual traits, both in healthy and psychiatric populations. We also found ongoing phase II clinical trials for oxytocin uses as an antipsychotic or anxiolytic. CONCLUSIONS:Given the research already conducted, we recommend investigation into the therapeutic use of oxytocin in adolescent populations for anxiety, psychosis, attachment disorders, and conduct disorder.
10.1002/hup.1212
A brief history of oxytocin and its role in modulating psychostimulant effects.
Carson Dean S,Guastella Adam J,Taylor Emily R,McGregor Iain S
Journal of psychopharmacology (Oxford, England)
Over the past century, the polypeptide oxytocin has played an important role in medicine with major highlights including the identification of its involvement in parturition and the milk let-down reflex. Oxytocin is now implicated in an extensive range of psychological phenomena including reward and memory processes and has been investigated as a treatment for several psychiatric disorders including addiction, anxiety, autism, and schizophrenia. In this review, we first provide an historical overview of oxytocin and describe key aspects of its physiological activity. We then outline some pharmacological limitations in this field of research before highlighting the role of oxytocin in a wide range of behavioral and neuronal processes. Finally, we review evidence for a modulatory role of oxytocin with regard to psychostimulant effects. Key findings suggest that oxytocin attenuates a broad number of cocaine and methamphetamine induced behaviors and associated neuronal activity in rodents. Evidence also outlines a role for oxytocin in the prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in both rodents and humans. Clinical trials should now investigate the effectiveness of oxytocin as a novel intervention for psychostimulant addiction and should aim to determine its specific role in the therapeutic properties of MDMA that are currently being investigated.
10.1177/0269881112473788
Intranasal delivery of antipsychotic drugs.
Katare Yogesh K,Piazza Justin E,Bhandari Jayant,Daya Ritesh P,Akilan Kosalan,Simpson Madeline J,Hoare Todd,Mishra Ram K
Schizophrenia research
Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses. We also review clinical studies in which intranasal delivery of peptides, like oxytocin (7 studies) and desmopressin (1), were used as an adjuvant to antipsychotic treatment with promising results. Experimental animal studies (17) investigating intranasal delivery of mainstream antipsychotic drugs have revealed successful targeting to the brain as suggested by pharmacokinetic parameters and behavioral effects. To improve delivery to the brain, nanotechnology-based carriers like nanoparticles and nanoemulsions have been used in several studies. However, human studies assessing intranasal delivery of mainstream antipsychotic drugs are lacking, and the potential toxicity of nanoformulations used in animal studies has not been explored. A brief discussion of future directions anticipates that if limitations of low aqueous solubility of antipsychotic drugs can be overcome and non-toxic formulations used, IN delivery (particularly targeting specific tissues within the brain) will gain more importance moving forward given the inherent benefits of IN delivery in comparison to other methods.
10.1016/j.schres.2016.11.027
Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice.
Caldwell H K,Stephens S L,Young W S
Molecular psychiatry
It has been previously suggested that oxytocin (Oxt) may act as a natural antipsychotic. To test this hypothesis, we investigated whether disruption of the oxytocin gene (Oxt-/-) made mice more susceptible to the psychosis-related effects of amphetamine (Amp), apomorphine (Apo) and phencyclidine (PCP). We examined drug-induced changes in the prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating deficits characteristic of several psychiatric and neurological disorders, including schizophrenia. We found that treatment with Amp, Apo and PCP all had effects on PPI. However, in Oxt-/- mice, but not Oxt+/+ mice, PCP treatment resulted in large PPI deficits. As PCP is a noncompetitive N-methyl-D-aspartic acid receptor antagonist, these findings suggest that the absence of Oxt alters the glutamatergic component of the PPI.
10.1038/sj.mp.4002150
Oxytocin and cardioprotection in diabetes and obesity.
Jankowski Marek,Broderick Tom L,Gutkowska Jolanta
BMC endocrine disorders
Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs.
10.1186/s12902-016-0110-1
Metabolic Effects of Oxytocin.
McCormack Shana E,Blevins James E,Lawson Elizabeth A
Endocrine reviews
There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears to modulate both homeostatic and reward-driven food intake, although the observed response depends on nutrient milieu (eg, obese vs. nonobese), clinical characteristics (eg, sex), and experimental paradigm. In animal models, OXT is anabolic to muscle and bone, which is consistent with OXT-induced weight loss occurring primarily via fat loss. In some human observational studies, circulating OXT concentrations are also positively associated with lean mass and bone mineral density. The impact of exogenous OXT on human obesity is the focus of ongoing investigation. Future randomized, placebo-controlled clinical trials in humans should include rigorous, standardized, and detailed assessments of adherence, adverse effects, pharmacokinetics/pharmacodynamics, and efficacy in the diverse populations that may benefit from OXT, in particular those in whom hypothalamic OXT signaling may be abnormal or impaired (eg, individuals with Sim1 deficiency, Prader-Willi syndrome, or craniopharyngioma). Future studies will also have the opportunity to investigate the characteristics of new OXT mimetic peptides and the obligation to consider long-term effects, especially when OXT is given to children and adolescents. (Endocrine Reviews XX: XX - XX, 2020).
10.1210/endrev/bnz012
Oxytocin as a potential pharmacological tool to combat obesity.
Journal of neuroendocrinology
The neuropeptide oxytocin (OT) has emerged as an important anorexigen in the regulation of food intake and energy balance. It has been shown that the release of OT and activation of hypothalamic OT neurons coincide with food ingestion. Its effects on feeding have largely been attributed to limiting meal size through interactions in key regulatory brain regions governing the homeostatic control of food intake such as the hypothalamus and hindbrain in addition to key feeding reward areas such as the nucleus accumbens and ventral tegmental area. Furthermore, the magnitude of an anorexigenic response to OT and feeding-related activation of the brain OT circuit are modified by the composition and flavor of a diet, as well as by a social context in which a meal is consumed. OT is particularly effective in reducing consumption of carbohydrates and sweet tastants. Pharmacologic, genetic, and pair-feeding studies indicate that OT-elicited weight loss cannot be fully explained by reductions of food intake and that the overall impact of OT on energy balance is also partly a result of OT-elicited changes in lipolysis, energy expenditure, and glucose regulation. Peripheral administration of OT mimics many of its effects when it is given into the central nervous system, raising the questions of whether and to what extent circulating OT acts through peripheral OT receptors to regulate energy balance. Although OT has been found to elicit weight loss in female mice, recent studies have indicated that sex and estrous cycle may impact oxytocinergic modulation of food intake. Despite the overall promising basic research data, attempts to use OT in the clinical setting to combat obesity and overeating have generated somewhat mixed results. The focus of this mini-review is to briefly summarize the role of OT in feeding and metabolism, address gaps and inconsistencies in our knowledge, and discuss some of the limitations to the potential use of chronic OT that should help guide future research on OT as a tailor-made anti-obesity therapeutic.
10.1111/jne.13106
Oxytocin: A Potential Therapeutic for Obesity.
Hong Soo Min,Ko Jeong-Kyung,Moon Jung-Joon,Kim Youl-Ri
Journal of obesity & metabolic syndrome
Oxytocin is a neuropeptide involved in the homeostasis of food consumption and energy; it affects hedonic eating. Studies in obese or binge-eating patients reported the hypophagic effect of oxytocin, which reduced caloric intake after administration. Several studies have demonstrated the effect of oxytocin's increasing energy intake, decreasing food consumption, and contributing to weight loss. Oxytocin's effects on food intake and metabolism suggest its therapeutic potential for treating obesity and binge eating.
10.7570/jomes20098
Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines.
Frontiers in neuroscience
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world and one of the leading indications for liver transplantation. It is one of the many manifestations of insulin resistance and metabolic syndrome as well as an independent risk factor for cardiovascular disease. There is growing evidence linking the incidence of NAFLD with psychiatric illnesses such as schizophrenia, bipolar disorder and depression mechanistically genetic, metabolic, inflammatory and environmental factors including smoking and psychiatric medications. Indeed, patients prescribed antipsychotic medications, regardless of diagnosis, have higher incidence of NAFLD than population norms. The mechanistic pharmacology of antipsychotic-associated NAFLD is beginning to emerge. In this review, we aim to discuss the pathophysiology of NAFLD including its risk factors, insulin resistance and systemic inflammation as well as its intersection with psychiatric illnesses.
10.3389/fnins.2022.1042442
Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators.
Vancampfort Davy,Vansteelandt Kristof,Correll Christoph U,Mitchell Alex J,De Herdt Amber,Sienaert Pascal,Probst Michel,De Hert Marc
The American journal of psychiatry
OBJECTIVE:Patients with bipolar disorder have high levels of cardiovascular disease risk factors. The presence of metabolic syndrome significantly influences future cardiovascular disease morbidity and mortality. The authors sought to clarify the prevalence and moderators of metabolic syndrome in bipolar patients, accounting for subgroup differences. METHOD:The authors searched MEDLINE, PsycINFO, EMBASE, and CINAHL through April 2012 for research reporting metabolic syndrome prevalence rates in bipolar patients. Medical subject headings "metabolic syndrome" and "bipolar" were used in the title, abstract, or index term fields. Manual searches were conducted using the reference lists from identified articles. RESULTS:The search yielded 81 articles in 37 publications (N=6,983). The overall metabolic syndrome rate was 37.3% (95% confidence interval [CI]=36.1-39.0) using any standardized metabolic syndrome criteria. Compared with general population groups, bipolar patients had higher metabolic syndrome rates (odds ratio=1.98; 95% CI=1.74-2.25). In bipolar patients, older age had a modest effect on the metabolic syndrome rate. The strongest moderator was the region in which the study took place, with the highest rates observed in New Zealand and Australia (64.2% [95% CI=38.3-83.9]) and North America (49.3% [95% CI=29.7-69.3]). Metabolic syndrome was significantly more prevalent in patients currently treated with antipsychotics (45.3% [95% CI=39.6-50.9] than in patients who were antipsychotic free (32.4% [95% CI=27.5-37.4]; odds ratio=1.72 [95% CI=1.24-2.38]). CONCLUSIONS:These findings strongly support the claim that patients with bipolar disorder are at high risk for metabolic syndrome and related cardiovascular morbidity and mortality and require regular monitoring and adequate preventive efforts and treatment for cardio-metabolic risk factors. These findings further suggest that the risk of metabolic syndrome is greater in bipolar patients taking prescribed antipsychotic medication.
10.1176/appi.ajp.2012.12050620
Prevalence and associated factors of obesity and overweight in Chinese patients with bipolar disorder.
Frontiers in psychiatry
Object:Despite abundant literature demonstrating a high prevalence of obesity and overweight in people with bipolar disorder (BD), little is known about this topic in China. Therefore, we assessed the prevalence and associated factors of obesity and overweight among inpatients with BD in our hospital, one of the largest public psychiatric hospitals in China. Methods:In this retrospective, cross-sectional study, 1,169 inpatients ≥18 years with BD during 2019 were included. Obesity was defined as having a BMI ≥25 kg/m, and overweight was defined as having a BMI from 23 kg/m to <25 kg/m. Binary logistic regression analysis was performed to identify factors associated with obesity and overweight. Results:The prevalence of obesity and overweight was 21.0% and 32.2% in patients with BD, respectively. Compared to patients with overweight and normal weight, patients with obesity were older, had a longer duration of BD and a longer length of hospital stay, had a higher prevalence of diabetes and hypertension, and had a higher level of all metabolic indices, except for HDL cholesterol. Binary logistic regression analysis showed that duration of BD, uric acid, alanine aminotransferase (ALT), triglyceride, and LDL cholesterol were significantly associated with obesity, and male sex and uric acid level were significantly associated with overweight ( < 0.05). Conclusions:Obesity and overweight were fairly prevalent in Chinese BD patients, and several factors were related to obesity and overweight. The results of the present study call for the need to implement early screening, prevention and interventions for obesity and overweight in patients with BD in China.
10.3389/fpsyt.2022.984829
Low prevalence of obesity and metabolic syndrome in never-treated chronic schizophrenia.
Padmavati Ramachandran,McCreadie Robin G,Tirupati Srinivasan
Schizophrenia research
INTRODUCTION:Antipsychotic medication and lifestyle factors are implicated in the high rates of obesity and metabolic syndrome in schizophrenia. While the two Consensus Statements made in 2004 concluded they were unclear whether psychiatric disorders per se accounted for increased prevalence of metabolic disorders several later studies have presented the case for an association between schizophrenia and metabolic disorders, especially impaired glucose metabolism and Type 2 diabetes mellitus, independent of antipsychotic drug treatment. METHODS:This is a comparative study of 51 patients with chronic schizophrenia who never received antipsychotic drug treatment and 51 healthy controls. Physical and laboratory assessments were made to measure body-mass index and diagnose metabolic syndrome using the International Diabetes Federation (2006) criteria. RESULTS:The study observed a significantly lower mean body-mass index in patients (19.4) than controls (22.7) and very low and comparable rates of metabolic syndrome (3.9% in patients, 7.8% in controls). DISCUSSION:Economic affordability and lifestyles modified by living conditions were discussed as factors underlying the high rates of underweight in the patient population and low rates of metabolic disorders in all the study subjects. The study concluded that schizophrenia in the absence of antipsychotic drug treatment is not a factor contributing to high prevalence of metabolic abnormalities. Lifestyle factors and the social and economic circumstances that drive them should be considered for better understanding and management of excess weight gain and metabolic abnormalities in people with schizophrenia.
10.1016/j.schres.2010.05.010
Prevalence and associated factors of overweight/obesity among severely ill psychiatric patients in Eastern Ethiopia: A comparative cross-sectional study.
PloS one
BACKGROUND:Globally, the burden of overweight and obesity is a major cardiovascular disease risk factor and is even higher among patients with psychiatric disorders compared to the general population. This is mainly due to the deleterious lifestyles characterized by physical inactivity, excessive substance use, and unhealthy diets common among patients with psychiatric disorders, as well as the negative metabolic effects of psychotropic medications. Despite these conditions being a high burden among patients with psychiatric illness, little attention is given to them during routine reviews in psychiatric clinics in most African nations, including Ethiopia. Therefore, this study aimed to estimate and compare the prevalence of and associated risk factors for overweight and obesity among patients with psychiatric illnesses. METHODS:A comparative cross-sectional study was conducted between severely ill psychiatric patients and non-psychiatric patients in Dire Dawa, Eastern Ethiopia. The study included 192 study participants (96 psychiatric patients and 96 non-psychiatric controls). Weight and height were measured for 192 study participants. Baseline demographic and clinical characteristics of psychiatric and non-psychiatric patients were described. The data were cleaned and analyzed using the Statistical Package for Social Sciences, Version 21. The intergroup comparisons were performed using an independent sample t-test and Chi-square tests. Logistic regression analysis was used to identify the association between overweight/obesity and the associated variables. RESULTS:The magnitude of overweight/obesity was significantly higher in the severely ill psychiatric groups (43.8%) than in the non-exposed controls (20.80%). The prevalence of overweight/obesity was highest in major depressive disorders (40%), followed by schizophrenia (32%), and bipolar disorder (28%). CONCLUSIONS:There was a high prevalence of obesity/overweight among psychiatric patients. Educational status, unemployment, and late stages of the disease were significant predictors of overweight/ obesity. Clinicians should be aware of the health consequences of overweight/obesity, and considering screening strategies as a part of routine psychiatric care is strongly recommended.
10.1371/journal.pone.0264461
Prevalence of underweight in patients with schizophrenia: A meta-analysis.
Sugawara Norio,Maruo Kazushi,Sugai Takuro,Suzuki Yutaro,Ozeki Yuji,Shimoda Kazutaka,Someya Toshiyuki,Yasui-Furukori Norio
Schizophrenia research
AIMS:Although the relationship between body mass index and all-cause mortality is U-shaped, underweight has received comparatively less attention than obesity. There is only limited evidence to date regarding underweight among patients with schizophrenia. This is the first meta-analysis to address the prevalence of underweight in these patients. METHODS:We conducted database searches (PubMed, PsycINFO) to identify studies examining underweight in patients with schizophrenia. In total, 17 studies (18 groups) with 45,474 patients were included; data were extracted independently by two authors. A meta-analysis was performed to calculate the pooled prevalence of underweight in patients. RESULTS:The pooled prevalence of underweight was 6.2% (95% CI=4.5-8.6) for the 18 groups, which included 45,474 patients with schizophrenia. The heterogeneity was I=98.9% (95% Cl=98.7-99.1%). Four studies with 4 groups, consisting of 30,014 individuals, focused on Japanese inpatients with schizophrenia. The pooled prevalence of underweight among inpatients in these 4 groups was 17.6% (95% CI=15.5-20.0). Fourteen studies were conducted with non-Japanese inpatients and included 14 groups of 15,460 patients with schizophrenia. The pooled prevalence of underweight in non-Japanese inpatients was 4.6% (95% CI=3.9-5.4). The proportion of underweight in the 18 groups significantly varied between Japanese inpatients and other patients. CONCLUSIONS:The results indicated that Japanese inpatients with schizophrenia have a high proportion of underweight. Future research should focus on evaluating interventions that target underweight.
10.1016/j.schres.2017.10.017
Higher prevalence of metabolic syndrome and related factors in patients with first-episode psychosis and schizophrenia: a cross-sectional study in Turkey.
Sahpolat Musa,Ari Mustafa
Nordic journal of psychiatry
BACKGROUND:Schizophrenia patients (SPP) have an increased risk of metabolic syndrome (MetS) and are twice more likely to experience diabetes mellitus and obesity than the general population. AIMS:The main purpose of this study was to assess the prevalence of MetS and its components in first-episode psychosis patients (FEPP) and SPP. METHODS:This study consisted a total of 38 untreated FEPP, 40 SPP and 41 randomly selected healthy volunteers admitted to the psychiatric outpatient clinic. The diagnosis of MetS was made based on Adult Treatment Panel III (ATP III), ATP III-A and International Diabetes Federation (IDF) criteria. RESULTS:The prevalence of MetS was 26.3, 28.9 and 31.5% according to ATP III, ATP III-A and IDF criteria in the FEPP, respectively. The prevalence of MetS was 37.5, 40 and 42.5% according to ATP III, ATP III-A and IDF criteria in the SPP, respectively. The prevalence of MetS was 9.7, 9.7 and 12.2% according to ATP III, ATP III-A and IDF criteria in the control group, respectively. The prevalence of MetS was higher in female patients than male patients based on all three diagnostic criteria. The MetS patients had a higher mean of age, a longer duration of disease, and treatment compared to patients without MetS. CONCLUSION:The current study found that FEPP and SPP had an increased prevalence of MetS. Especially, clinicians should pay attention to MetS in SPP due to the presence of risk factors, such as advanced age, being female, and long duration of disease and treatment.
10.1080/08039488.2020.1815080
Sex Differences in Body Mass Index and Obesity in Chinese Patients With Chronic Schizophrenia.
Li Qiongzhen,Chen Dachuan,Liu Tiebang,Walss-Bass Consuelo,de Quevedo Joao L,Soares Jair C,Zhao Jingping,Zhang Xiang Yang
Journal of clinical psychopharmacology
Sex differences in schizophrenia have been well recognized. However, sex differences in obesity associated with antipsychotics have received little systematic study. This study was conducted to compare sex difference effects of antipsychotics and related risk factors on obesity and body mass index (BMI) in Chinese patients with schizophrenia. A total of 204 inpatients with chronic schizophrenia (males/females = 140/66) were recruited. Demographic and clinical data were collected, and serum glucose and lipid levels were measured. The Positive and Negative Syndrome Scale (PANSS) was used to assess patients' psychopathology. The prevalence of obesity in female patients (21/66, 31.82%) was approximately 2 times that of male patients (22/140, 15.83%; P < 0.001) and women also had higher BMI than men (25.49 ± 4.42 kg/m versus 23.95 ± 3.67 kg/m; P < 0.005). Regression analyses showed that obesity was associated with type 2 diabetes (P < 0.05) and triglycerides (P < 0.05) in women, and limited to triglyceride in men (P < 0.01). Further correlation analysis showed that BMI was associated with the PANSS negative symptom subscore (P < 0.001) and the PANSS total score (P < 0.01) in men. In addition, women had higher low-density lipoprotein plasma levels than men. Our findings suggest that there are significant sex differences in bodyweight and obesity in chronic medicated patients with schizophrenia, with worse lipid metabolic dysfunction in female patients.
10.1097/JCP.0000000000000594
Body mass index, obesity, and psychopathology in patients with schizophrenia.
Subramaniam Mythily,Lam Max,Guo Meng En,He Vincent Y F,Lee Jimmy,Verma Swapna,Chong Siow Ann
Journal of clinical psychopharmacology
A number of studies have reported that patients with schizophrenia have a higher body mass index (BMI) than the general population. Few Asian studies have examined BMI in patients with schizophrenia. The aims of the current study were to evaluate the distribution of BMI and prevalence of obesity in a large sample of Chinese patients with schizophrenia (n = 973) and to examine the sociodemographic and clinical correlates of overweight (BMI ≥ 25 kg/m) and obesity (BMI ≥ 30 kg/m). There was a preponderance of patients who were overweight (58.7%) and obese (73.6%) as compared with control subjects. Regression modeling of clinical and symptom factors in schizophrenia patients revealed that females were almost twice as likely to be obese compared with males and patients with comorbid medical conditions were more likely to be obese compared with those who did not have a comorbid medical condition (odds ratio, 1.6). Those prescribed typical antipsychotic medications were 1.7 times more likely to be obese, whereas individuals prescribed with both typical and atypical antipsychotic medications were 2.2 times more likely to be obese as compared with those prescribed atypical antipsychotics. A significant predictor interaction for obesity was observed between sex and typical antipsychotics, sex and comorbid medical conditions, and years of education and comorbid medical conditions. The higher prevalence of obesity in patients with schizophrenia is a matter of clinical and public health concern; interventions to reduce weight to healthy levels would result in both improved health and quality of life among patients with schizophrenia.
10.1097/JCP.0000000000000058
Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management.
Manu P,Dima L,Shulman M,Vancampfort D,De Hert M,Correll C U
Acta psychiatrica Scandinavica
OBJECTIVE:To review recent advances in the epidemiology, pathobiology, and management of weight gain and obesity in patients with schizophrenia and to evaluate the extent to which they should influence guidelines for clinical practice. METHOD:A Medline literature search was performed to identify clinical and experimental studies published in 2005-2014 decade. RESULTS:Weight gain and obesity increase the risk of adult-onset diabetes mellitus and cardiovascular disorders, non-adherence with pharmacological interventions, quality of life, and psychiatric readmissions. The etiology includes adverse effects of antipsychotics, pretreatment/premorbid genetic vulnerabilities, psychosocial and socioeconomic risk factors, and unhealthy lifestyle. Patients with schizophrenia have higher intake of calories in the form of high-density food and lower energy expenditure. The inverse relationship between baseline body mass index and antipsychotic-induced weight gain is probably due to previous antipsychotic exposure. In experimental models, the second-generation antipsychotic olanzapine increased the orexigenic stimulation of hypothalamic structures responsible for energy homeostasis. CONCLUSION:The management of weight gain and obesity in patients with schizophrenia centers on behavioural interventions using caloric intake reduction, dietary restructuring, and moderate-intensity physical activity. The decision to switch antipsychotics to lower-liability medications should be individualized, and metformin may be considered for adjunctive therapy, given its favorable risk-benefit profile.
10.1111/acps.12445
Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: Results from the FACE-SZ cohort.
Godin O,Leboyer M,Gaman A,Aouizerate B,Berna F,Brunel L,Capdevielle D,Chereau I,Dorey J M,Dubertret C,Dubreucq J,Faget C,Gabayet F,Le Strat Y,Llorca P M,Misdrahi D,Rey R,Richieri R,Passerieux C,Schandrin A,Schürhoff F,Urbach M,Vidalhet P,Girerd N,Fond G,
Schizophrenia research
OBJECTIVE:Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. METHOD:240 SZ patients (age=31.4years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360μmol/L. RESULTS:MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR=5.9, IC95 [1.7-21.4]) and in subjects with high waist circumference (OR=3.1, IC95 [1.1-8.3]) or hypertriglyceridemia (OR=4.9, IC95 [1.9-13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. CONCLUSIONS:The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.
10.1016/j.schres.2015.07.047
Factors associated with overweight and obesity in schizophrenia, schizoaffective and bipolar disorders.
Chouinard Virginie-Anne,Pingali Samira M,Chouinard Guy,Henderson David C,Mallya Sonal G,Cypess Aaron M,Cohen Bruce M,Öngür Dost
Psychiatry research
Evidence suggests abnormal bioenergetic status throughout the body in psychotic disorders. The present study examined predictors of elevated body mass index (BMI) across diagnostic categories of schizophrenia, schizoaffective and bipolar disorders. In a cross-sectional study, we studied demographic and clinical risk factors for overweight and obesity in a well-characterized sample of 262 inpatients and outpatients with schizophrenia (n=59), schizoaffective disorder (n=81) and bipolar I disorder (n=122). Across the three diagnostic categories, the prevalence of overweight (29.4%) and obesity (33.2%) combined was 62.6% (164/262). Logistic regression analyses, adjusted for age, sex and ethnicity, showed that schizoaffective disorder, lifetime major depressive episode, presence of prior suicide attempt, and more than 5 lifetime hospitalizations were significantly associated with BMI≥25. Patients with schizophrenia had significantly lower risk for overweight and obesity. Overall, we found that affective components of illness were associated with elevated BMI in our cross-diagnostic sample. Our results show that patients with schizoaffective disorder have a greater risk for obesity. Identifying predictors of elevated BMI in patients with psychotic and mood disorders will help prevent obesity and related cardiovascular and cerebral complications. Future studies are needed to elucidate the mechanistic nature of the relationship between obesity and psychiatric illness.
10.1016/j.psychres.2016.01.024
Prevalence of Overweight and Obesity in People With Severe Mental Illness: Systematic Review and Meta-Analysis.
Frontiers in endocrinology
Aims:1) To determine the pooled prevalence of overweight and obesity in people with severe mental illness (SMI), overall and by type of SMI, geographical region, and year of data collection; and 2) to assess the likelihood of overweight and obesity, in people with SMI compared with the general population. Methods:PubMed, Medline, EMBASE, and PsycINFO databases were searched to identify observational studies assessing the prevalence of obesity in adults with SMI. Screening, data extraction and risk of bias assessments were performed independently by two co-authors. Random effect estimates for the pooled prevalence of overweight and obesity and the pooled odds of obesity in people with SMI compared with the general population were calculated. Subgroup analyses were conducted for types of SMI, setting, antipsychotic medication, region of the world, country income classification, date of data collection and sex. We assessed publication bias and performed a series of sensitivity analyses, excluding studies with high risk of bias, with low sample size and those not reporting obesity according to WHO classification. Result:120 studies from 43 countries were included, the majority were from high income countries. The pooled prevalence of obesity in people with SMI was 25.9% (95% C.I. = 23.3-29.1) and the combined pooled prevalence of overweight and obesity was 60.1% (95% C.I. = 55.8-63.1). Sub-Saharan Africa (13.0%, 95%C.I. = 6.7-25.1) and South Asia (17.7%, 95%C.I. = 10.5-28.5) had the lowest prevalence of obesity whilst North Africa and the Middle East (35.8%, 95%C.I. = 23.8-44.8) reported the highest prevalence. People with SMI were 3.04 more likely (95% C.I. = 2.42-3.82) to have obesity than the general population, but there was no difference in the prevalence of overweight. Women with schizophrenia were 1.44 (95% C.I. = 1.25-1.67) times more likely than men with schizophrenia to live with obesity; however, no gender differences were found among those with bipolar disorder. Conclusion:People with SMI have a markedly high prevalence and higher odds of obesity than the general population. This may contribute to the very high prevalence of physical health conditions and mortality in this group. People with SMI around the world would likely benefit from interventions to reduce and prevent obesity.
10.3389/fendo.2021.769309
Metabolic syndrome among older adults with schizophrenia spectrum disorder: Prevalence and associated factors in a multicenter study.
Abou Kassm Sandra,Hoertel Nicolas,Naja Wadih,McMahon Kibby,Barrière Sarah,Blumenstock Yvonne,Portefaix Christophe,Raucher-Chéné Delphine,Béra-Potelle Céline,Cuervo-Lombard Christine,Guerin-Langlois Christophe,Lemogne Cédric,Peyre Hugo,Kaladjian Arthur,Limosin Frédéric,
Psychiatry research
Metabolic syndrome and its associated morbidity and mortality have been well documented in adults with schizophrenia. However, data is lacking for their geriatric counterparts. We sought to investigate the frequency of screening and the prevalence of metabolic syndrome in older adults with schizophrenia, as well as its possible correlates, using the Cohort of individuals with schizophrenia Aged 55 years or more study (n = 353). We found that 42.2% (n = 149) of our sample was screened for metabolic syndrome. Almost half of those (n = 77; 51.7%) screened positive according to ATPIII criteria. Hypertension and abdominal obesity were the two most prevalent metabolic abnormalities. Screening was positively associated with male gender and urbanicity, and metabolic syndrome diagnosis was positively associated with cardiovascular disorders and consultation with a general practitioner (all p < 0.05). However, there were no significant associations of metabolic syndrome with socio-demographic or clinical characteristics, psychotropic medications, other medical conditions and other indicators of mental health care utilization. Our findings support that the prevalence of metabolic syndrome among older adults with schizophrenia spectrum disorder is high and screening is crucial mainly in those patients with hypertension and/or abdominal obesity. Factors at play might be different than those in the younger population.
10.1016/j.psychres.2019.03.036
Influencing factors of obesity in community patients with deficit schizophrenia: a cross-sectional study.
European journal of medical research
BACKGROUND:Obesity is very common in patients with schizophrenia. We aimed to evaluate the influencing factors of obesity in community patients with deficit schizophrenia, to provide implication for schizophrenia management in community. METHODS:We selected patients with deficit schizophrenia who lived in 10 communities in our city from March 1 to June 30, 2021. The characteristics of included schizophrenia patients were evaluated and analyzed. Pearson correlation analysis was conducted to evaluate the obesity and related characteristics. Logistic regression analyses were conducted to assess the risk factors of obesity in patients with schizophrenia. RESULTS:A total of 284 patients with schizophrenia were included, the incidence of obesity in patients with schizophrenia was 56.70%. gender (r = 0.619), waist circumference (r = 0.644), BMI (r = 0.891), diabetes (r = 0.698), FG (r = 0.582), triglyceride (r = 0.618), HDL-C (r = -0.644), LDL-C (r = 0.583), apolipoprotein B (r = 0.595), and PANSS score (r = 0.813) were all correlated with the obesity in patients with schizophrenia (all p < 0.05). Logistic regression analysis indicated that female (OR 2.129, 95% CI 1.615-3.022), waist circumference ≥ 90 cm (OR 3.814, 95% CI 2.778 ~ 4.312), diabetes (OR 2.856, 95% CI 1.905 ~ 3.448), FG ≥ 88 mg/dL (OR 1.551, 95% CI 1.284 ~ 2.183), triglyceride ≥ 160 mg/dL (OR 1.804, 95% CI 1.236-2.845), HDL-C ≤ 0.8 mmol/L (OR 2.032, 95% CI 1.614-3.079), LDL-C ≥ 2.0 mmol/L (OR 1.926, 95% CI 1.442-2.041) and apolipoprotein B ≥ 0.70 g/L (OR 2.119, 95% CI 1.658-2.873) were the risk factors of obesity in patients with schizophrenia (all p < 0.05). CONCLUSIONS:The obesity rate of patients with deficit schizophrenia in the community is high, and there are many associated risk factors. Early intervention targeted on those risk factors are warranted to reduce the obesity in schizophrenia patients.
10.1186/s40001-022-00706-y
Sex Differences in Obesity and Cognitive Function in Chinese Elderly Patients With Chronic Schizophrenia.
Frontiers in endocrinology
Background:It is well known that schizophrenia is associated with sex differences. However, no study has explored the sex differences in obesity and cognitive function in elderly Chinese patients with schizophrenia. Objective:This study aimed to compare sex differences in obesity and cognitive function in elderly Chinese individuals with schizophrenia. Methods:A total of 304 elderly patients with schizophrenia and 130 sex- and age-matched healthy controls from the community were recruited. Demographic, clinical, and lipid parameters were collected for all subjects. The Montreal Cognitive Assessment (MoCA) was used to assess the global cognitive functions of the participants, while the Positive and Negative Syndrome Scale (PANSS) was used to assess psychopathological symptoms in patients with schizophrenia. Results:Of the patients with schizophrenia, the prevalence of obesity in men and women was 11.7% (19/163) and 21.3% (30/141), respectively. The score (14.51 ± 6.504) of MOCA in elderly male patients with schizophrenia was significantly higher than that (11.40 ± 6.822) in female patients. There was a positive correlation between the MOCA scores and body mass index (BMI) (r=0.206, p=0.018) in male elderly patients with schizophrenia. Conversely, the MOCA scores of female elderly patients with schizophrenia did not correlate with BMI (p>0.05). However, we found no sex differences in obesity and cognition among control older adults. Conclusions:Our findings suggest that there are significant sex differences in obesity and cognitive function in elderly Chinese patients with schizophrenia.
10.3389/fendo.2022.742474
Diabetes in late-life schizophrenia: Prevalence, factors, and association with clinical symptoms.
Huo Lijuan,Lu Xiaobing,Wu Fengchun,Huang Xingbing,Ning Yuping,Zhang Xiang Yang
Journal of psychiatric research
OBJECTIVE:The prevalence of diabetes mellitus has been found to be higher in patients with schizophrenia. Older patients are the fastest-growing segment of the schizophrenia population. However, few studies have explored diabetes in older patients with schizophrenia. Therefore, this study aimed to determine the prevalence and characteristics of factors associated with diabetes in Chinese patients with late-life schizophrenia (LLS), which has not been reported in previous studies. METHODS:A total of 289 inpatients aged 60 or above who met the DSM-IV criteria for schizophrenia were recruited. The severity of psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Diabetes was diagnosed by fasting blood glucose tests, or oral glucose tolerance tests. RESULTS:The overall prevalence of diabetes in LLS patients was 25.3%. The prevalence of diabetes in female patients was significantly higher than that in male patients (35% vs. 21.53%). Other factors associated with diabetes included higher BMI, greater waistline (only for males), higher levels of triglyceride, and more severe positive symptoms. CONCLUSION:These results indicate that the prevalence of diabetes in LLS patients is similar to that in the age-matched general population. Female gender, excess weight and abdominal obesity, dyslipidemia, and clinical symptoms can be potential risk factors of diabetes in the LLS patient group.
10.1016/j.jpsychires.2020.09.026
Body mass index (BMI) and obesity in Nigerians with schizophrenia.
Nordic journal of psychiatry
BACKGROUND:Few Nigerian studies have examined BMI in people with schizophrenia. The aims of the present study were to assess the prevalence and distribution of obesity in Nigerians with schizophrenia and to examine the clinical correlates of BMI and obesity. METHODS:A total of 207 people with schizophrenia met the inclusion criteria and were evaluated for BMI.The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS), Social and Occupational Functioning Assessment Scale (SOFAS) were rated for all participants. Anthropometric measures such as weight and height were taken using a standard protocol. RESULTS:The prevalence of obesity was 12.6%. The non-obese participants were made up of underweight 24 (11.7%), normal weight 118 (57%) and overweight 38 (18.4%). Compared to non-obese participants, obese participants were older, more educated, more likely to be employed, had higher incomes, lower PANSS score (negative subscale), had fewer female participants, and better social and occupational functioning (<0.05). BMI was positively correlated with age and monthly income. In the adjusted model, age, gender and education were independently associated with obesity while only age was associated with BMI. CONCLUSION:The present study suggests that unlike in high-income countries, obese patients with schizophrenia in Nigeria have better social and psychological functioning than non-obese patients.
10.1080/08039488.2021.1926538
The prevalence, risk factors and clinical correlates of obesity in Chinese patients with schizophrenia.
Li Qiongzhen,Du Xiangdong,Zhang Yingyang,Yin Guangzhong,Zhang Guangya,Walss-Bass Consuelo,Quevedo João,Soares Jair C,Xia Haishen,Li Xiaosi,Zheng Yingjun,Ning Yuping,Zhang Xiang Yang
Psychiatry research
Obesity is a common comorbidity in schizophrenia. Few studies have addressed obesity in Chinese schizophrenia patients. The aims of this current study were to evaluate the prevalence, risk factors and clinical correlates of obesity in Chinese patients with schizophrenia. A total of 206 patients were recruited from a hospital in Beijing. Their clinical and anthropometric data together with plasma glucose and lipid parameters were collected. Positive and Negative Syndrome Scale (PANSS) was rated for all patients. Overall, 43 (20.9%) patients were obese and 67 (32.5%) were overweight. The obese patients had significantly higher glucose levels, triglyceride levels than non-obese patients. Females and patients with type 2 diabetes mellitus had increased risk for obesity. Correlation analysis showed that BMI was associated with sex, education levels, negative symptoms, total PANSS score, triglyceride levels and type 2 diabetes mellitus. Further stepwise regression analysis showed that sex, type 2 diabetes, education level, triglyceride and amount of smoking/day were significant predictors for obesity. Our study showed that the prevalence of obesity in Chinese patients with schizophrenia is higher than that in the general population. Some demographic and clinical variables are risk factors for obesity in schizophrenia.
10.1016/j.psychres.2016.12.041
Obesity in Chinese patients with chronic schizophrenia: Prevalence, clinical correlates and relationship with cognitive deficits.
Tian Yang,Liu Dianying,Wang Dongmei,Wang Jiesi,Xu Hang,Dai Qilong,Andriescue Elena C,Wu Hanjing E,Xiu Meihong,Chen Dachun,Wang Li,Chen Yiwen,Yang Ruilang,Wu Anshi,Wei Chang Wei,Zhang Xiangyang
Schizophrenia research
The prevalence of obesity in schizophrenia patients is high, especially in chronic and medicated patients. Few studies have explored the relationships between obesity, cognition and clinical correlates in patients with schizophrenia. This study was designed to assess the prevalence and clinical correlates of obesity and its relationship to cognitive impairment in Chinese patients with schizophrenia. We recruited 633 inpatients and collected clinical, demographic data and lipid parameters. The Positive and Negative Syndrome Scale (PANSS) and its five-factor model were adopted for psychopathological symptoms. The prevalence of comorbid obesity in schizophrenia patients was 16.4%. The plasma levels of glucose, triglyceride, low density lipoprotein (LDL), apolipoprotein B, and cholesterol were higher, but high density lipoprotein (HDL) levels were lower in obese patients than those in non-obese patients (all p < 0.05). Furthermore, obese patients had lower PANSS negative symptom, cognitive factor and total scores than non-obese patients (all p < 0.05). Correlation analysis showed a significant correlation between BMI and the following variables: age, marriage, gender, negative symptoms, general psychopathological symptoms, cognitive factor, PANSS total score, glucose, triglycerides, HDL, LDL, cholesterol and apolipoprotein B (all p < 0.05). Further multiple regression showed that PANSS cognitive factor, PANSS total score, and triglyceride were important independent predictors of obesity. Our results indicate a high prevalence of obesity in Chinese patients with chronic schizophrenia. Multiple demographics, clinical variables, and lipid parameters are associated with obesity in schizophrenia. Moreover, obesity appears to be a protective factor for psychological symptoms. However, not having objective assessments for cognition in this study is a limitation.
10.1016/j.schres.2019.10.017
Prevalence of obesity and clinical and metabolic correlates in first-episode schizophrenia relative to healthy controls.
Tian Yang,Wang Dongmei,Wei Gaoxia,Wang Jiesi,Zhou Huixia,Xu Hang,Dai Qilong,Xiu Meihong,Chen Dachun,Wang Li,Zhang Xiang Yang
Psychopharmacology
OBJECTIVE:People with schizophrenia exhibit a high obesity rate. However, little is known about the prevalence of obesity and its relationship with clinical symptoms and metabolic indicators in first-episode drug-naïve (FEDN) schizophrenia. METHODS:Demographic and lipid parameters were gathered from 297 FEDN schizophrenia and 325 healthy controls. The patients' symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS:The obesity rate of FEDN patients was 10.77%, similar to that of controls (10.5%). The prevalence of overweight plus obesity of patients was 44.8%, significantly higher than that of controls (36.6%). Compared with non-obese patients, obese patients had higher levels of cholesterol (4.81 ± 0.93 vs 4.22 ± 1.00 mmol/L), triglyceride (0.27 ± 0.21 vs 0.14 ± 0.24 mg/dL), low-density lipoprotein (0.48 ± 0.12 vs 0.40 ± 0.12 mg/dL), greater ratio of triglyceride/high-density lipoprotein (2.01 ± 1.23 vs 1.44 ± 1.26), and higher PANSS positive symptom subscale score (29.81 ± 6.29 vs 27.05 ± 6.15), general psychopathology subscale score (70.75 ± 11.74 vs 66.87 ± 11.37), and total score (149.81 ± 21.08 vs 140.64 ± 21.58), but lower high-density lipoprotein level (1.09 ± 0.21 vs 1.27 ± 0.34 mg/dL) (all p < 0.05). Correlation analysis revealed that body mass index (BMI) was positively correlated with triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, triglyceride/high-density lipoprotein ratio, PANSS positive symptoms, general psychopathology, and total scores (all p < 0.05, r = 0.124 ~ 0.335). Multiple regression analysis confirmed that PANSS positive symptoms, total score, and cholesterol level were significantly associated with BMI (all p < 0.05, β: 0.126-0.162). CONCLUSION:There was no significant difference in the prevalence of obesity between FEDN patients and the control group. Moreover, BMI was positively associated with positive symptom severity in FEDN patients.
10.1007/s00213-020-05727-1
The prevalence and independent influencing factors of obesity and underweight in patients with schizophrenia: a multicentre cross-sectional study.
Wang Juan,Zhang Yulong,Yang Yating,Liu Zhiwei,Xia Lei,Li Wenzheng,Li Zhongxiang,Xie Xinhui,Deng Wenfeng,Zhang Kai,Liu Huanzhong
Eating and weight disorders : EWD
BACKGROUND:Few studies have investigated the weight of patients with schizophrenia in China. OBJECTIVE:The aim of this study was to analyse the prevalence, clinical characteristics and influencing factors of obesity and underweight in patients with chronic schizophrenia in China. METHODS:A total of 325 patients with schizophrenia and 172 sex- and age-matched healthy controls from the community were recruited. Socio-demographic data and laboratory measurements were collected for all subjects. Using the Positive and Negative Syndrome Scale (PANSS), we evaluated the psychiatric symptoms of patients with schizophrenia. According to the body mass index (BMI) criteria in China, BMI ≥ 28 kg/m indicates obesity, and BMI < 18.5 kg/m indicates underweight. RESULTS:Of the patients with schizophrenia, 16.3% were obese, and 6.8% were underweight; 11.0% of the healthy controls were obese, and 3.5% were underweight. There was no difference between the two groups in the prevalence of obesity and underweight. After controlling for relevant variables, the obesity rate remained non significant, but the underweight rate appeared to be different. The multinomial regression analysis revealed that among the patients with schizophrenia, female sex, triglyceride level and LDL level were independent risk factors for obesity and that HDL level was an independent protective factor against obesity. In contrast, male sex and HDL level were independent risk factors for underweight. CONCLUSION:We found that the patients with schizophrenia had an increased rate of underweight and some factors related to weight. LEVEL OF EVIDENCE:Level V, descriptive study.
10.1007/s40519-020-00920-9
Psychological and psychiatric aspects of treatment of obesity and nonalcoholic fatty liver disease.
Stewart Karen E,Levenson James L
Clinics in liver disease
Chronic illnesses incur a tremendous cost to American lives in dollars and quality of life. Outcomes in these illnesses are often affected by psychological, behavioral, and pharmacologic issues related to mental illness and psychological symptoms. This article focuses on psychological and psychiatric issues related to the treatment of obesity and nonalcoholic fatty liver disease (NAFLD), including available weight-loss interventions, the complex relationship between psychiatric disorders and obesity, and special considerations regarding use of psychiatric drugs in patients with or at risk for NAFLD and obesity. Recommendations for collaborative care of individuals with comorbid NAFLD and psychological disorders/symptoms are discussed.
10.1016/j.cld.2012.05.007
Olanzapine leads to nonalcoholic fatty liver disease through the apolipoprotein A5 pathway.
Li Rong,Zhu Wenqiang,Huang Piaopiao,Yang Yang,Luo Fei,Dai Wen,Shen Li,Pei Wenjing,Huang Xiansheng
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
The antipsychotic drug olanzapine was reported to induce nonalcoholic fatty liver disease (NAFLD), whereas the underlying mechanism remains incompletely understood. This study investigated whether apolipoprotein A5 (apoA5) and sortilin, two interactive factors involved in NAFLD pathogenesis, are implicated in olanzapine-induced NAFLD. In our study, at week 8, olanzapine treatment successfully induced hepatic steatosis in female C57 BL/6 J mice, which was independent of body weight gain. Likewise, olanzapine effectively mediated hepatocyte steatosis in HepG2 cells characterized by substantially elevated intracellular lipid droplets. Increased plasma triglyceride concentration and decreased plasma apoA5 levels were observed in mice treated with 8-week olanzapine. Surprisingly, olanzapine markedly enhanced hepatic apoA5 protein levels in mice, without a significant effect on rodent hepatic ApoA5 mRNA. Our in vitro study showed that olanzapine reduced apoA5 protein levels in the medium and enhanced apoA5 protein levels in hepatocytes, whereas this drug exerted no effect on hepatocyte APOA5 mRNA. By transfecting APOA5 siRNA into HepG2 cells, it was demonstrated that APOA5 knockdown effectively reversed olanzapine-induced hepatocyte steatosis in vitro. In addition, olanzapine drastically increased sortilin mRNA and protein levels in vivo and in vitro. Interestingly, SORT1 knockdown reduced intracellular apoA5 protein levels and increased medium apoA5 protein levels in vitro, without affecting intracellular APOA5 mRNA levels. Furthermore, SORT1 knockdown greatly ameliorated hepatocyte steatosis in vitro. This study provides the first evidence that sortilin inhibits the hepatic apoA5 secretion that is attributable to olanzapine-induced NAFLD, which provides new insight into effective strategies against NAFLD for patients with schizophrenia administered olanzapine.
10.1016/j.biopha.2021.111803
Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity.
Peng Luting,Wu Su,Zhou Nan,Zhu Shanliang,Liu Qianqi,Li Xiaonan
BMC pediatrics
BACKGROUND:With the increasing number of children with obesity worldwide, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease among children. It is necessary to recognize the risk factors of NAFLD for prevention in childhood since NAFLD is asymptomatic in the early stage. OBJECTIVES:The objective of this study was to investigate possible risk factors of NAFLD in children with obesity, providing evidence for monitoring and prevention strategies at an early stage for obese children with NAFLD. METHODS:Data were collected from 428 children and adolescents aged 6-16 years recruited from the Children's Hospital at Nanjing Medical University from September 2015 to April 2018 and analyzed. Based on a combination of ultrasound results and alanine transaminase levels, subjects were divided into three groups: simple obesity (SOB), simple steatosis (SS), and nonalcoholic fatty hepatitis (NASH). Blood biochemical examination included glucose, insulin, uric acid, lipid profile and liver enzymes. RESULTS:Among 428 children with obesity, 235 (54.9%) had SS and 45 (10.5%) had NASH. Body mass index, body mass index standard deviation score (BMI-SDS), waist circumference, body fat, liver enzymes, uric acid and HOMA-IR level were significantly higher in the NASH group than in the SS and SOB groups (p < 0.001). 53.3% of the SS group and 49.8% of the NASH group had metabolic syndrome, significantly more than in the SOB group (19.6%, p < 0.001). After adjustment for confounding factors, logistic regression models revealed that NASH was associated with BMI-SDS ≥ 3, gender, hyperuricemia and insulin resistance. CONCLUSIONS:The prevalence of NASH in children with obesity is closely related to high BMI-SDS, gender, insulin resistance and hyperuricemia. These findings provide evidence that monitoring risk factors of childhood obesity can assist in developing prevention strategies for liver disease at an early stage.
10.1186/s12887-021-02595-2
Are mood disorders and obesity related? A review for the mental health professional.
McElroy Susan L,Kotwal Renu,Malhotra Shishuka,Nelson Erik B,Keck Paul E,Nemeroff Charles B
The Journal of clinical psychiatry
OBJECTIVE:We reviewed evidence regarding a possible relationship between mood disorders and obesity to better inform mental health professionals about their overlap. METHOD:We performed a MEDLINE search of the English-language literature for the years 1966-2003 using the following terms: obesity, overweight, abdominal, central, metabolic syndrome, depression, mania, bipolar disorder, binge eating, morbidity, mortality, cardiovascular, diabetes, cortisol, hypertriglyceridemia, sympathetic, family history, stimulant, sibutramine, antiobesity, antidepressant, topiramate, and zonisamide. We evaluated studies of obesity (and related conditions) in persons with mood disorders and of mood disorders in persons with obesity. We also compared studies of obesity and mood disorders regarding phenomenology, comorbidity, family history, biology, and pharmacologic treatment response. RESULTS:The most rigorous clinical studies suggest that (1). children and adolescents with major depressive disorder may be at increased risk for developing overweight; (2). patients with bipolar disorder may have elevated rates of overweight, obesity, and abdominal obesity; and (3). obese persons seeking weight-loss treatment may have elevated rates of depressive and bipolar disorders. The most rigorous community studies suggest that (1). depression with atypical symptoms in females is significantly more likely to be associated with overweight than depression with typical symptoms; (2). obesity is associated with major depressive disorder in females; and (3). abdominal obesity may be associated with depressive symptoms in females and males; but (4). most overweight and obese persons in the community do not have mood disorders. Studies of phenomenology, comorbidity, family history, biology, and pharmacologic treatment response of mood disorders and obesity show that both conditions share many similarities along all of these indices. CONCLUSION:Although the overlap between mood disorders and obesity may be coincidental, it suggests the two conditions may be related. Clinical and theoretical implications of this overlap are discussed, and further research is called for.
Prevalence of obesity, metabolic syndrome, diabetes and risk of cardiovascular disease in a psychiatric inpatient sample: results of the Metabolism in Psychiatry (MiP) Study.
Barton Barbara B,Zagler Anja,Engl Katharina,Rihs Leonie,Musil Richard
European archives of psychiatry and clinical neuroscience
The information on prevalence of obesity, diabetes, metabolic syndrome (MetS) and cardiovascular risk (CVR) and on sociodemographic variables available in patients with psychiatric diseases about to be treated with weight gain-associated medication (e.g., clozapine, mirtazapine, quetiapine) is limited. In a naturalistic study, psychiatric inpatients (age: 18-75) of all F diagnoses according to ICD-10, who were about to be treated with weight gain-associated medication, were included. Demographic variables were assessed as well as biological parameters to calculate the Body Mass Index (BMI), MetS, diabetes and CVR. A total of 163 inpatients were included (60.1% male; mean age: 39.8 (± 15.1, 18-75 years). The three most common disorders were depression (46.0%), bipolar disorder (20.9%) and drug addiction (20.2%). The three most common pharmacotherapeutic agents prescribed were quetiapine (29.4%), mirtazapine (20.9%) and risperidone (12.9%). Of the included inpatients 30.1% were overweight, 17.2% obese, and 26.9% and 22.4% fulfilled the criteria for a MetS according to the International Diabetes Federation (IDF) and the National Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III), respectively, 3.8% had (pre)diabetes and 8.3% had a moderate and 1.9% a high CVR according to the Prospective Cardiovascular Münster (PROCAM) score. Detailed information is reported on all assessed parameters as well as on subgroup analyses concerning sociodemographic variables. The results suggest that psychiatric patients suffer from multiple metabolic disturbances in comparison to the general population. Monitoring weight, waist circumference, blood pressure and cholesterol regularly is, therefore, highly relevant.
10.1007/s00406-019-01043-8
A prospective, longitudinal study of metabolic syndrome in patients with bipolar disorder and schizophrenia.
Malhotra Nidhi,Kulhara Parmanand,Chakrabarti Subho,Grover Sandeep
Journal of affective disorders
BACKGROUND:Although cross sectional studies have evaluated the prevalence of metabolic syndrome (MetS) in patients with bipolar patients (BPAD), data from longitudinal studies are limited. AIM:To assess the prevalence of MetS in patients with BPAD, to observe the change in prevalence rate over a period of 6 months, to assess the prevalence of sub-threshold MetS (i.e., patients fulfilling one or two criteria of MetS) and to compare patients with BPAD and schizophrenia on the above mentioned parameters. METHODOLOGY:Seventy five patients with BPAD and 53 patients with schizophrenia were initially evaluated for MetS and then followed up for a period of 6 months. RESULTS:According to consensus definition, prevalence of MetS at baseline was 40% in BPAD group and 32% in schizophrenia group. Over 6 months of follow-up the prevalence of MetS increased by 8% and 9.4% in the BPAD and the schizophrenia groups respectively. There was no significant difference between the two groups on any of the assessments. Another 28-32% of patients in the BPAD group also fulfilled two criteria and 13-17% fulfilled at least one criterion of MetS at different points of assessment. Similarly, 19-26% of the patients with schizophrenia met at least two and 23-26% of the patients fulfilled at least one criterion of MetS. LIMITATION:The study was limited by small sample size, inclusion and the relatively short follow-up period. CONCLUSION:40% patients with BPAD and 32% with schizophrenia have MetS and the prevalence of MetS increases by 8-9.4% over 6 months.
10.1016/j.jad.2013.03.010
Higher Prevalence of Metabolic Syndrome in Child-adolescent Patients with Bipolar Disorder.
Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
OBJECTIVE:Previous studies have indicated a convergent and bidirectional relationship between metabolic syndrome (MetS) and bipolar disorder (BD). As most of these studies focused mainly on adults diagnosed with BD, our study aims to investigate and characterize metabolic disturbances in child-adolescents diagnosed with BD. METHODS:We retrospectively examined the medical records of psychiatric hospitalizations with admitting diagnosis of BD in child-adolescents (age ＜ 18 years). Body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure were primary variables. National Cholesterol Education Program criteria were used to define MetS. Reference group data was obtained from the National Health and Nutrition Examination Survey study. Statistical analyses included t tests, chi-square tests, and Fisher's exact tests. RESULTS:We identified 140 child-adolescent patients with BD (mean age = 15.12 ± 1.70 years, 53% male). MetS was significantly more common in BD compared to the reference group: 14% (95% confidence interval [95% CI] 8-20) vs. 6.7% (95% CI 4.1-9.2), = 0.001 with no significant difference by sex. MetS components were higher in the BD group, particularly BMI ≥ 95% (25% vs. 11.8%, ＜ 0.001) and high blood pressure (17% vs. 8%, = 0.05). Moreover, female patients had lower odds of high blood pressure (odds ratio = 0.24 [95% CI 0.08-0.69], = 0.005). CONCLUSION:Compared with the general child-adolescent population, the prevalence of MetS was significantly higher in patients with BD of same age. This reiterates the notion of an increased risk of MetS in patients diagnosed with BD; and thus, further exploration is warranted.
10.9758/cpn.2020.18.2.279
Does metabolic syndrome or its component factors alter the course of bipolar disorder? A systematic review.
Giménez-Palomo Anna,Gomes-da-Costa Susana,Dodd Seetal,Pachiarotti Isabella,Verdolini Norma,Vieta Eduard,Berk Michael
Neuroscience and biobehavioral reviews
Metabolic syndrome (MetS) and its component factors, obesity, hypertension, dyslipidaemia and insulin resistance, have shown a bidirectional relationship with the prevalence and severity of bipolar disorder (BD). A systematic search of electronic databases (Pubmed, PsycINFO, clinicaltrials.gov) was conducted to explore and integrate current evidence about the role of MetS and its component factors with clinical outcomes of BD. Thirty-four articles met the inclusion criteria. Studies were grouped by the metabolic factors assessed, which included MetS, obesity and body mass index (BMI), dyslipidaemia, impaired glucose metabolism (IGM), diabetes mellitus and hypertension. They were then classified according to outcomes such as course of episodes, rapid cycling, suicidal behavior, treatment response, and global and cognitive functioning. Although current evidence remains controversial in most aspects of clinical outcomes, metabolic risk factors could alter the course of BD, with worse global functioning, poorer treatment response and a chronic course of illness, as well as enhancing rapid cycling. Further research is needed to elucidate the role of each risk factor in the mentioned outcomes.
10.1016/j.neubiorev.2021.11.026
Prevalence of type 2 diabetes mellitus, impaired fasting glucose, general obesity, and abdominal obesity in patients with bipolar disorder: A systematic review and meta-analysis.
Liu Yuhan Karida,Ling Susan,Lui Leanna M W,Ceban Felicia,Vinberg Maj,Kessing Lars Vedel,Ho Roger C,Rhee Taeho Greg,Gill Hartej,Cao Bing,Mansur Rodrigo B,Lee Yena,Rosenblat Joshua,Teopiz Kayla M,McIntyre Roger S
Journal of affective disorders
OBJECTIVES:The study herein aimed to assess the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), as well as general and abdominal obesity in patients with bipolar disorder (BD). We also compared the prevalence of T2DM and general obesity in patients with BD with age- and gender-matched healthy controls. METHODS:A systematic search of Embase, Medline, PubMed, and APA PsycArticles was conducted from inception to June 2021 without language restrictions. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) modified for case-control studies. RESULTS:A total of forty-nine studies were included in this analysis. The pooled prevalence of T2DM was 9.6% (95% CI, 7.3-12.2%). Patients with BD had a nearly 1.6 times greater risk of developing T2DM compared to their age- and gender-matched controls (RR=1.57, 95% CI 1.36-1.81, p<0.001). In the present analysis, IFG is defined as a fasting plasma glucose (FPG) ≥ 100 mg/dL (FPG≥100) with a prevalence of 22.4% (95% CI, 16.7-28.7%), or as an FPG equal to or greater than 110 mg/d (FPG≥110) with a prevalence of 14.8% (95% CI, 10.8-19.3%). The prevalence of general obesity (BMI≥30 kg/m) was 29.0% (95% CI, 22.8-35.6%); the risk of obesity was almost twice the rate reported in patients with BD compared to controls (RR=1.67, 95% CI 1.32-2.12, p<0.001). We also observed that more than half of the BD participants had abdominal obesity (i.e., prevalence of 51.1%; 95% CI, 45.0-57.3%). LIMITATIONS:A significant degree of heterogeneity was detected. Sources of heterogeneity included differences in study designs, inclusion criteria, measurement tools, and data analysis methods. CONCLUSION:Bipolar disorder is associated with a higher prevalence of T2DM, IFG, general obesity, and abdominal obesity. Type 2 diabetes mellitus and obesity are significantly more prevalent in patients with BD than in their age- and gender-matched controls. STUDY REGISTRATION:CRD42021258431.
10.1016/j.jad.2021.12.110
Diagnosis and treatment of depression in adults with comorbid medical conditions: a 52-year-old man with depression.
Whooley Mary A
JAMA
Approximately 1 in 10 primary care patients has major depressive disorder, and its presence is associated with poor health outcomes in numerous medical conditions. Using the case of Mr J, a 52-year-old man with depressive symptoms and several comorbid medical conditions, diagnosis and treatment of depression are discussed. Specific topics include evidence regarding appropriate depression screening and diagnosis, the importance of team-based care, patient self-management, exercise, structured psychotherapy, pharmacotherapy, monitoring of therapy, and indications for referral.
10.1001/jama.2012.3466
Depression, anxiety, and nonalcoholic steatohepatitis.
Elwing Jill E,Lustman Patrick J,Wang Hanlin L,Clouse Ray E
Psychosomatic medicine
OBJECTIVE:Nonalcoholic steatohepatitis (NASH) is a morbid liver disease with limited treatment. Depression and anxiety have been associated recently with insulin resistance and inflammatory states, factors that are relevant to the development of NASH. We hypothesized that depression and anxiety would be more prevalent in NASH patients and predict more severe histological findings on liver biopsy. METHODS:Histories of major depressive disorder (MDD) and generalized anxiety disorder (GAD) were determined using a structured interview and DSM-IV criteria in 36 NASH subjects and 36 matched controls without liver disease who had undergone cholecystectomy. Histological changes on liver biopsy in NASH subjects were age-adjusted and compared in subjects with and without psychiatric disorders. A multivariate model incorporating other potential risk factors for NASH (female sex, body mass index, waist-to-hip ratio, and presence of diabetes) was used to determine independent effects of MDD and GAD on severity of histological findings. RESULTS:NASH subjects had significantly increased lifetime rates of MDD (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.4-10.2; p = .018) and GAD (OR 5.0, 95% CI, 1.7-14.9; p = .005). The onset of psychiatric illness preceded diagnosis of liver disease by 18 to 20 years. Each psychiatric disorder was associated with more severe histological features (p < .05 for each), the effect of GAD on fibrosis stage persisting in the multivariate model. CONCLUSIONS:MDD and GAD are overrepresented in NASH subjects and are associated with more advanced liver histological abnormalities. Additional investigation will be required to determine if depression and anxiety affect the development or progression of NASH and serve as modifiable risk factors.
10.1097/01.psy.0000221276.17823.df
Depression and Cognitive Impairment-Extrahepatic Manifestations of NAFLD and NASH.
Biomedicines
Non-alcoholic fatty liver disease (NAFLD) and its complication non-alcoholic steatohepatitis (NASH) are important causes of liver disease worldwide. Recently, a significant association between these hepatic diseases and different central nervous system (CNS) disorders has been observed in an increasing number of patients. NAFLD-related CNS dysfunctions include cognitive impairment, hippocampal-dependent memory impairment, and mood imbalances (in particular, depression and anxiety). This review aims at summarizing the main correlations observed between NAFLD development and these CNS dysfunctions, focusing on the studies investigating the mechanism(s) involved in this association. Growing evidences point at cerebrovascular alteration, neuroinflammation, and brain insulin resistance as NAFLD/NASH-related CNS manifestations. Since the pharmacological options available for the management of these conditions are still limited, further studies are needed to unravel the mechanism(s) of NAFLD/NASH and their central manifestations and identify effective pharmacological targets.
10.3390/biomedicines8070229
Association Between Anxiety and Depression and Nonalcoholic Fatty Liver Disease.
Choi Ji Min,Chung Goh Eun,Kang Seung Joo,Kwak Min-Sun,Yang Jong In,Park Boram,Yim Jeong Yoon
Frontiers in medicine
Depression and anxiety disorder are frequently seen in patients with nonalcoholic fatty liver disease (NAFLD). However, the associations between mood disorders and NAFLD have not been fully evaluated. In this study, we investigated the relationship between NAFLD and depression or anxiety in a Korean population. We conducted a retrospective cross-sectional study that included subjects who underwent abdominal ultrasonography and completed a symptom questionnaire for a routine health check-up. NAFLD was diagnosed and graded according to the ultrasonography findings. Depression and anxiety were assessed using the Beck Depression Inventory and State-Trait Anxiety Inventory, respectively. Among the total of 25,333 subjects, the mean age was 47 years (men, 56.2%), and the prevalence rate of NAFLD was 30.9%. In the multivariate analysis, NAFLD showed a significant association with depression [adjusted odds ratio (OR) 1.43 and 95% confidence interval (CI) 1.14-1.80, = 0.002] in women. Severe NAFLD significantly correlated with state anxiety and trait anxiety (adjusted OR 1.84 and 95% CI 1.01-3.37, = 0.047 and adjusted OR 2.45 and 95% CI 1.08-4.85, = 0.018, respectively) in women. There was a higher tendency of women with NAFLD to suffer from depression with increase in steatosis, and severe stage of steatosis was significantly associated with anxiety in the female compared to non-NAFLD. Understanding the association between NAFLD and mood disorders may have clinical implications for reducing the prevalence of comorbidities.
10.3389/fmed.2020.585618
Nonalcoholic Fatty Liver Disease Increases the Risk of Anxiety and Depression.
Labenz Christian,Huber Yvonne,Michel Maurice,Nagel Michael,Galle Peter R,Kostev Karel,Schattenberg Jörn M
Hepatology communications
Nonalcoholic fatty liver disease (NAFLD), depression, and anxiety disorders are frequent diseases, and data on mutual influence are inconsistent. The aim of this study was to explore the incidence of depression and anxiety in a large primary care cohort in Germany and to study the impact of NAFLD over a 10-year time frame. Patients with NAFLD diagnosed between 2010 and 2015 were matched to a cohort without NAFLD controlling for age, sex, physician, index year, and Charlson comorbidity index. The primary outcome of the study was the incidence of depression, anxiety, and first prescription of antidepressant drugs. We compared 19,871 patients with NAFLD to 19,871 matched controls. Within 10 years of the index date, 21.2% of patients with NAFLD and 18.2% of controls were diagnosed with depression ( < 0.001). On regression analysis, the hazard ratio (HR) for incidence of depression was 1.21 ( < 0.001). This association was similar for the endpoint of the first prescription of antidepressant drugs (HR, 1.21; < 0.001). Anxiety disorders were diagnosed in 7.9% of patients with NAFLD and 6.5% of controls during the observation time ( = 0.003). The HR for incidence of anxiety was 1.23 ( < 0.001). This association remained significant in women ( < 0.001), while there was only a trend in men (HR, 1.15; 95% confidence interval, 0.99-1.34; < 0.067). The risk of developing anxiety disorders was higher in younger patients. NAFLD constitutes an independent risk factor for emerging depression and anxiety even after controlling for confounding comorbidities.
10.1002/hep4.1541
Non-Alcoholic Fatty Liver Disease (NAFLD) and Potential Links to Depression, Anxiety, and Chronic Stress.
Shea Sue,Lionis Christos,Kite Chris,Atkinson Lou,Chaggar Surinderjeet S,Randeva Harpal S,Kyrou Ioannis
Biomedicines
Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.
10.3390/biomedicines9111697
Metabolic indexes of obesity in patients with common mental disorders in stable stage.
BMC psychiatry
BACKGROUND:Obesity is a serious worldwide public health problem, especially for people with mental disorders. AIM:To explore the related factors of obesity by analyzing the metabolic indexes of patients with common mental disorders in stable stage. METHODS:Five hundred seventy-six subjects with major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia (SCZ) were included, who received fixed drug dose and routine drug treatment for 2 years or more. Their venous blood was collected, and the blood metabolic indexes were analyzed. RESULTS:BD and SCZ are more prone to obesity than MDD. Multiple linear regression analysis showed that the value of BMI increased with the increase of age(B = 0.084, p < 0.001), TG(B = 0.355, p = 0.024), LDL(B = 0.697, p < 0.001), LDH(B = 0.011, p = 0.002), SCr(B = 0.051, p < 0.001), UA(B = 0.014, p < 0.001), HbA1c(B = 0.702, p = 0.004) and hsCRP(B = 0.101, p < 0.001). And It decreased with the increase of HDL(B = -1.493, p < 0.001). DISCUSSION:People with mental disorders should regularly check blood indicators and strengthen weight management to reduce the risk of obesity and promote their health.
10.1186/s12888-022-03752-2
Hypertension and psychosis.
Postgraduate medical journal
Hypertension, a prevalent component of metabolic syndrome (MetS), is a well-known risk factor for cardiovascular diseases (CVD). Psychosis is a feature in the schizophrenia spectrum. Meta-analysis suggests that the prevalence of hypertension in schizophrenia and related disorders is 39%. This may be explained by a unidirectional association between hypertension and psychosis, in that psychosis can be a causative factor of hypertension via antipsychotic medication, inflammation and irregular autonomic nervous system activity through multiple mechanisms. Obesity is a side effect of antipsychotic medication and is a risk factor for hypertension. Obesity leads to raised blood pressure, atherosclerosis, increased triglyceride concentration and decreased high-density lipoprotein concentration. Inflammation accompanies hypertension and obesity. In recent years, the role of inflammation in the onset of psychosis has been increasingly recognised. It underlies the immune dysregulation observed in both schizophrenia and bipolar disorder. Interleukin-6, a marker and driver of inflammation, is related to obesity and plays a role in the pathogenesis of MetS and hypertension. The lack of preventive care of hypertension and other MetS risk factors for patients on antipsychotic medication is reflected in the high incidence of CVD in this population. It is important to detect and treat MetS and hypertension in patients with psychosis in order to reduce cardiovascular morbidity and mortality in this population.
10.1136/postgradmedj-2021-141386
Obesity and frontal-striatal brain structures in offspring of individuals with bipolar disorder: Results from the global mood and brain science initiative.
Mansur Rodrigo B,McIntyre Roger S,Cao Bo,Lee Yena,Japiassú Letícia,Chen Kun,Lu Rui,Lu Weicong,Chen Xiaodong,Li Ting,Xu Guiyun,Lin Kangguang
Bipolar disorders
OBJECTIVES:To compare frontal-striatal brain volumes between offspring of individuals with bipolar disorder (BD) and healthy controls; to investigate the associations of body mass index (BMI) and age with brain volumes; and to assess the moderating effects of BMI and age on the relationship between risk status and structural brain differences. METHODS:We cross-sectionally assessed structural regional and global brain volumes using magnetic resonance imaging and BMI among 53 BD offspring subjects, stratified by risk status, and 23 non-BD offspring controls (aged 8-28 years). Analyses of variance and covariance and linear regression analyses were conducted to investigate the associations between BMI and measures of brain volume, as well as the interaction effects between age, BMI, and risk status on brain volumes. RESULTS:After adjusting for age, sex, and intracranial volume, higher BD risk status was associated with lower bilateral cerebellar cortical and right pars orbitalis volumes. Higher BMI was significantly associated with greater brain volumes in frontal and subcortical structures. A significant interaction effect between BMI and risk status was observed in right middle frontal volume. The moderating effect of BMI on brain volume was most robustly observed among subjects aged 14-19 years and less robustly observed among those aged 20-28 years; BMI and brain volumes were negatively correlated among subjects aged 8-13 years. CONCLUSIONS:Alterations in brain structures in individuals at risk for BD may be moderated by BMI. Obesity among individuals with a family history of BD may confer additional risk, particularly in mid-adolescence.
10.1111/bdi.12559
Adverse effects of obesity on cognitive functions in individuals at ultra high risk for bipolar disorder: Results from the global mood and brain science initiative.
McIntyre Roger S,Mansur Rodrigo B,Lee Yena,Japiassú Letícia,Chen Kun,Lu Rui,Lu Weicong,Chen Xiaodong,Li Ting,Xu Guiyun,Lin Kangguang
Bipolar disorders
BACKGROUND:The burden of illness associated with bipolar disorder (BD) warrants early pre-emption/prevention. Prediction models limited to psychiatric phenomenology have insufficient predictive power. Herein, we aimed to evaluate whether the presence of overweight/obesity is associated with greater cognitive decline in individuals at high risk (HR) or ultra high risk (UHR) for BD. METHODS:We conducted a retrospective analysis to investigate the moderational role of body mass index (BMI) on measures of cognitive function. Subjects between the ages of 8 and 28 years with a positive family history of BD were compared to age-matched controls with a negative family history of BD. Subjects with at least one biological parent with bipolar I/II disorder were further stratified into UHR or HR status by the presence or absence, respectively, of subthreshold hypomanic, major depressive, attenuated psychotic, and/or attention-deficit/hyperactivity disorder symptoms. RESULTS:A total of 36 individuals at HR for BD, 33 individuals at UHR for BD, and 48 age-matched controls were included in the analysis. Higher BMI was significantly associated with lower performance on measures of processing speed (i.e. Brief Assessment of Cognition in Schizophrenia-symbol coding: r=-.186, P=.047) and attention/vigilance (i.e. Continuous Performance Test-Identical Pairs: r=-.257, P=.006). There were trends for negative correlations between BMI and measures of working memory (i.e. Wechsler Memory Scale-III Spatial Span: r=-0.177, P=.059) and overall cognitive function (i.e. Measurement and Treatment Research to Improve Cognition in Schizophrenia composite score: r=-.157, P=.097). Negative associations between BMI and cognitive performance were significantly stronger in the UHR group than in the HR group, when compared to controls. CONCLUSIONS:Individuals at varying degrees of risk for BD exhibit greater cognitive impairment as a function of co-existing overweight/obesity. Prediction models for BD may be substantively informed by including information related to overweight/obesity and, perhaps, other general medical conditions that share pathology with BD. Our findings herein, as well as the salutary effects of bariatric surgery on measures of cognitive function in obese populations, provide the rationale for hypothesizing that mitigating excess weight in individuals at elevated risk for BD may forestall or prevent declaration of illness.
10.1111/bdi.12491
Prevalence and risk factors for non-suicidal self-injury among patients with depression or bipolar disorder in China.
Wang Lu,Liu Jun,Yang Yuan,Zou Haiou
BMC psychiatry
BACKGROUNDS:Non-suicidal self-injury is a serious health problem among patients with depression or bipolar disorder. However, few studies within the Chinese context have investigated the prevalence of NSSI and its risk factors in above populations. The purpose of this study was to investigate the prevalence of non-suicidal self-injury and its risk factors in patients with depression or bipolar disorder in China. METHODS:The final sample comprised of 394 inpatients(M = 29.71; SD = 11.95) with depression or bipolar disorder from two psychiatric hospitals in Beijing, China. A General Demographic Data Form, the Non-suicidal Self-injury Questionnaire(NSSI-Q), Impulsivity Item and the Adverse Childhood Experiences-International Questionnaire(ACE-IQ) were completed by all patients. RESULTS:Of the 394 patients examined, 245(62.2%) of this sample reported NSSI in past year. Of the 245 patients with NSSI, 135(55.1%) were diagnosed with depression and 110(44.9%) were diagnosed with bipolar disorder. The most common methods of NSSI for female was "pinching"(23.1%) and "scratching"(22.8%), while for male it was "hiting hard objects"(12.7%). By multivariate regression analysis, young age, unemployment, a higher monthly family income, single, impulsivity, long duration of illness and ACEs were risk factors for NSSI in patients with depression and bipolar disorder(P<0.05). CONCLUSIONS:Our study points to the fact that there was an unfortunate message about the prevalence of NSSI among patients with depression or bipolar disorder in China. It is necessary not only to raise the awareness of NSSI in families and society, but also to formulate targeted assessment and intervention. Moreover, future research should not only focus on individuals being hospitalized, but should be representative of individuals treated at home or in the community because there are no national statistics on NSSI among such patients in China.
10.1186/s12888-021-03392-y
Trajectories of body mass index change in first episode of mania: 3-year data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).
Hu Chen,Torres Ivan J,Qian Hong,Wong Hubert,Halli Priyanka,Dhanoa Taj,Ahn Sharon,Wang Gang,Bond David J,Lam Raymond W,Yatham Lakshmi N
Journal of affective disorders
BACKGROUND:Overweight/obesity is common in patients with bipolar disorder (BD). However, little is known about longitudinal trends in body mass index (BMI) in patients with BD. Furthermore, most studies on the association between BMI and clinical outcomes are restricted by retrospective and cross-sectional designs. This study uses prospectively-gathered data from a first episode mania (FEM) cohort to examine the trajectories of BMI change and analyze their association with clinical outcomes during a 3-year period. METHODS:A total of 110 FEM patients receiving maintenance treatment and 57 healthy subjects were included. The comparisons of BMI trajectories were examined using linear mixed-effects models. The effects of BMI on time to any mood episode were assessed by Cox proportional-hazards models. RESULTS:The estimated mean BMI in FEM patients significantly increased from 24.0kg/m to 25.4kg/m within 6 months. FEM patients had a significant BMI increase trend over the entire 3 years follow-up, which was not observed in the control group. No significant difference in BMI trajectory between patient subgroups (baseline normal-weight vs. overweight/obese; male vs. female) was observed. BMI increase predicted an increased risk of recurrence during follow-up visits (HR=1.50, 95% CI: 1.06-2.13; p=0.02). LIMITATIONS:Naturalistic design does not allow the accurate assessments of the impact of pharmacologic treatments on BMI. CONCLUSIONS:FEM patients showed a significantly increased BMI trajectory compared to healthy subjects. Furthermore, BMI increase is independently associated with an increased risk of recurrence to a new mood episode during 3-year follow-up. Thus, weight control prevention is needed in the early course of BD.
10.1016/j.jad.2016.08.048
BDNF and BMI effects on brain structures of bipolar offspring: results from the global mood and brain science initiative.
Mansur R B,Brietzke E,McIntyre R S,Cao B,Lee Y,Japiassú L,Chen K,Lu R,Lu W,Li T,Xu G,Lin K
Acta psychiatrica Scandinavica
OBJECTIVE:To compare brain-derived neurotrophic factor (BDNF) levels between offspring of individuals with bipolar disorders (BD) and healthy controls (HCs) and investigate the effects of BDNF levels and body mass index (BMI) on brain structures. METHOD:Sixty-seven bipolar offspring and 45 HCs were included (ages 8-28). Structural images were acquired using 3.0 Tesla magnetic resonance imaging. Serum BDNF levels were measured using enzyme-linked immunosorbent assay. Multivariate and univariate analyses of covariance were conducted. RESULTS:Significantly higher BDNF levels were observed among bipolar offspring, relative to HCs (P > 0.025). Offspring status moderated the association between BDNF and BMI (F =4.636, P = 0.034). After adjustment for relevant covariates, there was a trend for a significant interaction of group and BDNF on neuroimaging parameters (Wilks'λ F =1.463, P = 0.052), with significant effects on cerebellar white matter and superior and middle frontal regions. Brain volume and BDNF were positively correlated among HCs and negatively correlated among bipolar offspring. Interactions between BDNF and BMI on brain volumes were non-significant among HCs (Wilks'λ F =2.229, P = 0.357), but significant among bipolar offspring (Wilks'λ F =2.899, P = 0.028). CONCLUSION:Offspring status and BMI moderate the association between BDNF levels and brain structures among bipolar offspring, underscoring BDNF regulation and overweight/obesity as key moderators of BD pathogenesis.
10.1111/acps.12822
Eating behavior and obesity in bipolar disorder.
Bernstein Emily E,Nierenberg Andrew A,Deckersbach Thilo,Sylvia Louisa G
The Australian and New Zealand journal of psychiatry
OBJECTIVES:Individuals with bipolar disorder are more frequently overweight or obese than the general population, but the reasons for this association are unknown. The aim of this study is to further understand the etiology of overweight and obesity in bipolar disorder. METHODS:We invited patients in a specialty outpatient bipolar clinic to complete the Eating Inventory. Patients provided self-reported restraint, disinhibition, and perceived hunger as well as general perceptions of dietary intake. RESULTS:Sixty-two individuals (37 female) between the ages of 18 and 67 (M = 41.5, SD = 13.38) and with an average body mass index (BMI) of 27.18 (SD = 5.71) completed the survey. Disinhibition and perceived hunger were positively correlated with BMI and self-reported difficulty eating healthy foods. Restraint was positively correlated with healthy eating (ps < .05). Stepwise linear regressions revealed that hunger was the most significant predictor of BMI (F(1) = 8.134, p = .006). Those participants with bipolar I or II disorder reported greater hunger scores (p < .01) and difficulty eating healthily (p < .05) than those without a full diagnosis. CONCLUSIONS:These results suggest that disinhibition and perception of hunger may be linked to the disproportionately high rate of obesity in bipolar disorder.
10.1177/0004867414565479
High Prevalence of Metabolic Syndrome Among Adolescents and Young Adults With Bipolar Disorder.
Li Christine,Birmaher Boris,Rooks Brian,Gill Mary Kay,Hower Heather,Axelson David A,Dickstein Daniel P,Goldstein Tina R,Liao Fangzi,Yen Shirley,Hunt Jeffrey,Iyengar Satish,Ryan Neal D,Strober Michael A,Keller Martin B,Goldstein Benjamin I
The Journal of clinical psychiatry
OBJECTIVE:Despite abundant literature demonstrating increased metabolic syndrome (MetS) prevalence and important clinical correlates of MetS among middle-age adults with bipolar disorder, little is known about this topic among adolescents and young adults early in their course of bipolar disorder. We therefore examined this topic in the Course and Outcome of Bipolar Youth (COBY) study. METHODS:A cross-sectional, retrospective study was conducted of 162 adolescents and young adults (mean ± SD age = 20.8 ± 3.7 years; range, 13.6-28.3 years) with bipolar disorder (I, II, or not otherwise specified, based on DSM-IV) enrolled in COBY between 2000 and 2006. MetS measures (blood pressure, glucose, high-density lipoprotein cholesterol [HDL-C], triglycerides, and waist circumference), defined using the International Diabetes Federation criteria, were obtained at a single timepoint. Mood, comorbidity, and treatment over the 6 months preceding the MetS assessment were evaluated using the Longitudinal Interval Follow-Up Evaluation. RESULTS:The prevalence of MetS in the sample was 19.8% (32/162). Low HDL-C (56.5%) and abdominal obesity (46.9%) were the most common MetS criteria. MetS was nominally associated with lower lifetime global functioning at COBY intake (odds ratio [OR] = 0.97, P = .06). MetS was significantly associated with percentage of weeks in full-threshold pure depression (OR = 1.07, P = .02) and percentage of weeks receiving antidepressant medications (OR = 1.06, P = .001) in the preceding 6 months. MetS was not associated with manic symptoms or medications other than antidepressants. CONCLUSIONS:The prevalence of MetS in this sample was at least double compared to the general population. Moreover, MetS is associated with increased burden of depression symptoms in this group. Management of early-onset bipolar disorder should integrate strategies focused on modifying MetS risk factors.
10.4088/JCP.18m12422
Quantification of diet quality utilizing the rapid eating assessment for participants-shortened version in bipolar disorder: Implications for prospective depression and cardiometabolic studies.
Journal of affective disorders
OBJECTIVES:Recognizing bipolar disorder as a multi-system metabolic condition driven, in part, by binge eating behavior and atypical depressive symptoms, this study aimed to quantify diet quality and evaluate clinical correlates in a bipolar disorder cohort. METHODS:Participants from the Mayo Clinic Bipolar Disorder Biobank (n = 734) completed the Rapid Eating Assessment for Participants - Shortened version (REAP-S) to determine diet quality. The average REAP-S score for a U.S. omnivorous diet is 32 (range 13 to 39) with higher scores indicating healthier diet. Demographic variables were collected in a standardized clinical questionnaire. Depressive symptoms were assessed by the Bipolar Inventory of Symptoms Scale. Cardiometabolic variables were retrieved from the electronic health record. Associations between continuous variables and REAP-S scores (total, 'healthy foods' and 'avoidance of unhealthy foods') were assessed using linear regression. RESULTS:Overall, our sample had a mean REAP-S score of 27.6 (4.9), suggestive of a lower diet quality than the average general population in the US. There was a significant inverse relationship between mean REAP-S lower scores with increased BMI, waist circumference, disordered eating and depression. All these associations were significantly stronger in female participants. LIMITATIONS:EHR cross-sectional data. CONCLUSIONS:Our data suggest unhealthy diet quality in bipolar disorder is associated with depression, obesity and cardiometabolic abnormalities. Additional work is encouraged to prospectively track mood and diet quality to further understand the bidirectional relationship and clarify if dietary interventions can positively impact mood. Further delineating potential sex differences in diet quality and depression may provide greater appreciation of modifiable risk factors for future cardiometabolic burden.
10.1016/j.jad.2022.05.037
Bipolar Disorder and Obesity: Contributing Factors, Impact on Clinical Course, and the Role of Bariatric Surgery.
Reilly-Harrington Noreen A,Feig Emily H,Huffman Jeff C
Current obesity reports
PURPOSE OF REVIEW:Bipolar disorder (BD) is a severe, common, and chronic affective disorder. This review highlights the BD and obesity connection and the role of treatments for obesity in this population. RECENT FINDINGS:Patients with BD are at a significantly increased risk for obesity, as compared to those without BD, with obesity serving as a proxy for severity and predictor of poorer outcome. BD is characterized by substantial medical burden, with obesity-related conditions contributing to premature mortality. Pharmacotherapy for BD can cause weight gain and may be moderated by binge eating behavior. Bariatric surgery may be the most robust intervention for weight loss in patients with stable BD, but access may be limited. There is a greater need for interventions to prevent weight gain in BD, the development weight-neutral medications for BD, and more research into the role of bariatric surgery for patients with BD.
10.1007/s13679-018-0322-y
Effects of metabolic syndrome and obesity on suicidality in individuals with bipolar disorder.
Journal of affective disorders
BACKGROUND:The prevalence of metabolic syndrome and overweight/obesity is increased in bipolar disorder (BD) compared to the general population and is related to suicidality. The aim of this study was to examine the association between both the rate of suicidal ideation and suicide attempts and metabolic variables in individuals with BD. METHODS:Anthropometric measures, socio-demographic data, suicide history and serum lipid levels were measured in 215 individuals with BD. Individuals were divided into normal weight, overweight and obese according to their body mass index (BMI), and metabolic syndrome was assessed using "The International Diabetes Federation"-criteria. RESULTS:Of the 215 individuals studied, 80.9% reported suicidal ideation, 35.3% reported at least one suicide attempt and 30.7% were diagnosed with metabolic syndrome. Both metabolic syndrome and BMI were not related to suicide attempts. However, individuals with normal weight had more suicidal ideation than overweight individuals, while obese individuals did not differ from either group. Furthermore, there was no association between suicide attempts or suicidal ideation and serum lipid levels. LIMITATIONS:The cross-sectional design of the study, a non-standardized questionnaire for suicidality, and not controlling the medication intake are limiting factors. CONCLUSION:Contrary to expectations, a difference was found in the BMI categories and suicidal ideation, but not suicide attempts. Serum lipid levels were found to be unsuitable as possible biomarkers for suicidality in individuals with BD. Special attention should be paid to suicidal ideation and BMI rather than metabolic syndrome or lipid values when treating suicidal individuals with BD.
10.1016/j.jad.2022.05.062
Neurococognitive and neuroimaging correlates of obesity and components of metabolic syndrome in bipolar disorder: a systematic review.
Bora Emre,McIntyre Roger S,Ozerdem Aysegul
Psychological medicine
BACKGROUND:Individuals with bipolar disorder (BD) have a higher prevalence of obesity and metabolic syndrome (MetS) compared with the general population. Obesity and MetS are associated with cognitive deficits and brain imaging abnormalities in the general population. Obesity and components of MetS might potentially associate with neuroimaging and neurocognitive findings in BD. METHODS:A literature search of studies investigating the association between obesity (and other components of MetS) and neurocognitive and neuroimaging findings in BD was conducted. In addition to a systematic review, a random-effects meta-analysis was conducted when sufficient data were available. RESULTS:Twenty-three studies were included in the current systematic review. Overweight/obese patients were significantly associated with impaired neurocognition compared normal weight individuals with BD (d = 0.37). The most robust association between obesity and cognitive deficits in BD was observed in the cognitive subdomain of executive functions (d = 0.61). There was also evidence for a significant relationship between cognitive impairment in BD and other components of MetS including hypertension, dyslipidemia, and diabetes. Overweight/obese individuals with BD had more pronounced brain imaging abnormalities than normal weight individuals with BD. CONCLUSIONS:Obesity and related cardiovascular risk factors significantly are associated with more severe cognitive and brain imaging abnormalities in BD. Medical co-morbidities can potentially contribute to functional decline observed in some patients throughout the course of BD.
10.1017/S0033291718003008
Violent suicide attempt history in elderly patients with bipolar disorder: The role of sex, abdominal obesity, and verbal memory: Results from the FACE-BD cohort (FondaMental Advanced center of Expertise for Bipolar Disorders).
Lengvenyte Aiste,Aouizerate Bruno,Aubin Valerie,Loftus Joséphine,Marlinge Emeline,Belzeaux Raoul,Dubertret Caroline,Gard Sebastien,Haffen Emmanuel,Schwan Raymund,Llorca Pierre-Michel,Passerieux Christine,Roux Paul,Polosan Mircea,Etain Bruno,Leboyer Marion, ,Courtet Philippe,Olié Emilie
Journal of affective disorders
BACKGROUND:Bipolar disorder (BD) is a chronic, lifelong condition, associated with increased risk of obesity, cognitive impairment, and suicidal behaviors. Abdominal obesity and a higher risk of violent suicide attempt (SA) seem to be shared correlates with older age, BD, and male sex until middle age when menopause-related female body changes occur. This study aimed at assessing the role of abdominal obesity and cognition in the violent SA burden of individuals with BD. METHODS:From the well-defined nationwide cohort FACE-BD (FondaMental Advanced center of Expertise for Bipolar Disorders), we extracted data on 619 euthymic BD patients that were 50 years or older at inclusion. Cross-sectional clinical, cognitive, and metabolic assessments were performed. SA history was based on self-report. RESULTS:Violent SA, in contrast to non-violent and no SA, was associated with higher waist circumference, abdominal obesity and poorer California Verbal Learning Test short-delay free recall (CVLT-SDFR) (ANOVA, p < .001, p = .014, and p = .006). Waist circumference and abdominal obesity were associated with violent SA history independently of sex, BD type and anxiety disorder (Exp(B) 1.02, CI 1.00-1.05, p = .018; Exp(B) 2.16, CI 1.00-4.64, p = .009, accordingly). In an exploratory model, waist circumference and CVLT-SDFR performance mediated the association between male sex and violent SA. LIMITATIONS:Cross-sectional design and retrospective reporting. CONCLUSIONS:Violent SA history was associated with abdominal obesity and poorer verbal memory in older age BD patients. These factors were interlinked and might mediate the association between male sex and violent SA.
10.1016/j.jad.2021.09.097
Obesity and metabolic comorbidity in bipolar disorder: do patients on lithium comprise a subgroup? A naturalistic study.
Prillo Jake,Soh Jocelyn Fotso,Park Haley,Beaulieu Serge,Linnaranta Outi,Rej Soham
BMC psychiatry
BACKGROUND:Bipolar disorders (BD) are associated with increased prevalence of obesity and metabolic syndrome (MetS). Nevertheless, there is a wide range in prevalence estimates, with little known about the contributions of pharmacotherapy. It has been suggested that lithium might have a more favorable metabolic profile. We hypothesized that lithium use is associated with less increased body mass index (BMI), MetS, and type II diabetes, when compared with non-lithium users (those on anticonvulsants, second-generation antipsychotics). METHODS:Cross-sectional study of 129 patients aged 18-85 with bipolar disorder, followed at tertiary care clinics in Montreal. Patients using lithium were compared with those not on lithium, for body mass index and metabolic syndrome. RESULTS:The prevalence of obesity and metabolic syndrome in the sample of lithium-using patients with BD was 42.4 and 35.7% respectively, with an average BMI of 29.10 (+/- 6.70). Lithium and non-lithium groups did not differ in BMI or prevalence of MetS. However, compared to the non-lithium group, lithium users had lower hemoglobin A1C (5.24 +/- 0.53 versus 6.01 +/- 1.83, U = 753.5, p = 0.006) and lower triglycerides (1.46 +/- 0.88 versus 2.01 +/- 1.25, U = 947, p = 0.020). CONCLUSIONS:There is a high prevalence of obesity and metabolic syndrome among patients with bipolar disorder. However, this did not appear to be associated with lithium use, when compared to those not on lithium. The lithium subgroup was also associated with lower prevalence of type II diabetes. Future prospective and intervention studies with larger sample sizes are necessary to further explore the association between lithium and insulin resistance, as well as its underlying mechanisms.
10.1186/s12888-021-03572-w
Interventions for the management of obesity in people with bipolar disorder.
The Cochrane database of systematic reviews
BACKGROUND:Bipolar disorder is one of the most common serious mental illnesses, affecting approximately 60 million people worldwide. Characterised by extreme alterations in mood, cognition, and behaviour, bipolar disorder can have a significant negative impact on the functioning and quality of life of the affected individual. Compared with the general population, the prevalence of comorbid obesity is significantly higher in bipolar disorder. Approximately 68% of treatment seeking bipolar patients are overweight or obese. Clinicians are aware that obesity has the potential to contribute to other physical health conditions in people with bipolar disorder, including diabetes, hypertension, metabolic syndrome, cardiovascular disease, and coronary heart disease. Cardiovascular disease is the leading cause of premature death in bipolar disorder, happening a decade or more earlier than in the general population. Contributing factors include illness-related factors (mood-related factors, i.e. mania or depression), treatment-related factors (weight implications and other side effects of medications), and lifestyle factors (physical inactivity, poor diet, smoking, substance abuse). Approaches to the management of obesity in individuals with bipolar disorder are diverse and include non-pharmacological interventions (i.e. dietary, exercise, behavioural, or multi-component), pharmacological interventions (i.e. weight loss drugs or medication switching), and bariatric surgery. OBJECTIVES:To assess the effectiveness of interventions for the management of obesity in people with bipolar disorder. SEARCH METHODS:We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) and the Cochrane Central Register for Controlled Trials (CENTRAL) to February 2019. We ran additional searches via Ovid databases including MEDLINE, Embase, and PsycInfo to May 2020. We searched the World Health Organization (WHO) trials portal (International Clinical Trials Registry Platform (ICTRP)) and ClinicalTrials.gov. We also checked the reference lists of all papers brought to full-text stage and all relevant systematic reviews. SELECTION CRITERIA:Randomised controlled trials (RCTs), randomised at the level of the individual or cluster, and cross-over designs of interventions for management of obesity, in which at least 80% of study participants had a clinical diagnosis of bipolar disorder and comorbid obesity (body mass index (BMI) ≥ 30 kg/m²), were eligible for inclusion. No exclusions were based on type of bipolar disorder, stage of illness, age, or gender. We included non-pharmacological interventions comprising dietary, exercise, behavioural, and multi-component interventions; pharmacological interventions consisting of weight loss medications and medication switching interventions; and surgical interventions such as gastric bypass, gastric bands, biliopancreatic diversion, and vertical banded gastroplasty. Comparators included the following approaches: dietary intervention versus inactive comparator; exercise intervention versus inactive comparator; behavioural intervention versus inactive comparator; multi-component lifestyle intervention versus inactive comparator; medication switching intervention versus inactive comparator; weight loss medication intervention versus inactive comparator; and surgical intervention versus inactive comparator. Primary outcomes of interest were changes in body mass, patient-reported adverse events, and quality of life. DATA COLLECTION AND ANALYSIS:Four review authors were involved in the process of selecting studies. Two review authors independently screened the titles and abstracts of studies identified in the search. Studies brought to the full-text stage were then screened by another two review authors working independently. However, none of the full-text studies met the inclusion criteria. Had we included studies, we would have assessed their methodological quality by using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions. We intended to combine dichotomous data using risk ratios (RRs), and continuous data using mean differences (MDs). For each outcome, we intended to calculate overall effect size with 95% confidence intervals (CIs). MAIN RESULTS:None of the studies that were screened met the inclusion criteria. AUTHORS' CONCLUSIONS:None of the studies that were assessed met the inclusion criteria of this review. Therefore we were unable to determine the effectiveness of interventions for the management of obesity in individuals with bipolar disorder. Given the extent and impact of the problem and the absence of evidence, this review highlights the need for research in this area. We suggest the need for RCTs that will focus only on populations with bipolar disorder and comorbid obesity. We identified several ongoing studies that may be included in the update of this review.
10.1002/14651858.CD013006.pub2
Bedroom light exposure at night and obesity in individuals with bipolar disorder: A cross-sectional analysis of the APPLE cohort.
Esaki Yuichi,Obayashi Kenji,Saeki Keigo,Fujita Kiyoshi,Iwata Nakao,Kitajima Tsuyoshi
Physiology & behavior
Obesity and overweight are highly prevalent in individuals with bipolar disorder and are associated with a risk of developing not only physical but also mental problems. The current study aimed to determine the association between bedroom light exposure at night and obesity in individuals with bipolar disorder. This cross-sectional study enrolled 200 outpatients with bipolar disorder. The light intensity in the bedroom between bedtime and rising time was measured for seven consecutive nights using a portable photometer. Body mass index (BMI) was determined using self-reported height and weight, and obesity was defined as a BMI ≥ 25 kg/m. The overall prevalence of obesity was 44%. In the multivariable logistic regression analysis adjusted for age, gender, use of psychiatric medications, sleep parameters, and physical activity, the odds ratio (OR) for obesity was significantly higher in the group exposed to an average light intensity ≥ 3 lux (n = 112) than in the group exposed to an average light intensity < 3 lux (n = 88) (OR, 2.13; 95% confidence interval, 1.19-4.21; P = 0.01). Furthermore, individuals exposed to an average light intensity ≥ 3 lux were significantly higher body weight (adjusted mean, 68.7 vs. 64.4 kg; P = 0.03) and BMI (adjusted mean, 25.6 vs. 24.2 kg/m; P = 0.04) than those exposed to an average light intensity < 3 lux. A significant association was observed between bedroom light exposure at night and obesity in patients with bipolar disorder. Further longitudinal investigations are necessary to clarify this association.
10.1016/j.physbeh.2020.113281
Effects of a Mobile Health Intervention to Promote HIV Self-testing with MSM in China: A Randomized Controlled Trial.
Zhu Xiaofang,Zhang Wenhan,Operario Don,Zhao Yue,Shi Anxia,Zhang Zhihua,Gao Pan,Perez Ashley,Wang Jun,Zaller Nickolas,Yang Cui,Sun Yehuan,Zhang Hongbo
AIDS and behavior
This study tested a mobile health (mHealth) intervention program entitled WeTest, delivered via the WeChat mobile app, to promote oral HIV self-testing (HIVST) among MSM in Hefei, China. A total of 100 MSM participants enrolled, completed baseline assessment, were randomly assigned to intervention or control, and completed 6-month follow-up surveys. Intervention participants (n = 50) received two oral HIVST kits and access to WeTest, a private WeChat group which provided app-based messages and referrals to health services related to HIV. Control participants (n = 50) received two oral HIVST kits only. All participants received instructions to upload photographic results of their oral HIVST, which were sent to the project counselor via a secure WeChat online portal; immediate contact and referrals were made to any participants who tested HIV-positive. In GEE analyses adjusting for time effects and baseline confounders, intervention participants had significantly higher rates of HIV testing (adjusted rate ratio RR = 1.99, 95% confidence interval (CI) 1.07-3.84) and, in particular, higher rates of testing via oral HIVST (adjusted RR = 2.17, 95% CI 1.08-4.37) compared with the control group. Significant time effects were also found such that all participants, regardless of group allocation, had significantly higher rates of reporting consistent condom use with main partners (adjusted RR = 18.13, 95% CI 5.19-63.31) and with non-main partners (adjusted RR = 5.33, 95% CI 2.35-12.08). Findings from this study provide evidence for the feasibility, acceptability and preliminary effects of this mHealth approach to promoting oral HIVST among MSM in China.
10.1007/s10461-019-02452-5
Treating refractory obsessive-compulsive disorder with transcranial direct current stimulation: An open label study.
Harika-Germaneau Ghina,Heit Damien,Chatard Armand,Thirioux Berangere,Langbour Nicolas,Jaafari Nemat
Brain and behavior
BACKGROUND:Obsessive-compulsive disorder (OCD) is a complex disorder with 40%-60% of patients' refractory to treatment. Transcranial direct current stimulation (tDCS) has been shown to induce potent and long-lasting effects on cortical excitability. The aim of the present clinical trial was to evaluate the therapeutic efficacy and tolerability of cathodal tDCS over the supplementary motor area (SMA) in treatment-resistant OCD patients. METHODS:Twenty-one treatment-resistant OCD outpatients received 10 sessions of tDCS. Each treatment session consisted of 2 mA stimuli for 30 min. The cathode was positioned over the bilateral SMA and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment, one-month follow-up, and three-month follow-up. Response to treatment was defined as at least a decrease of 35% on the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and a score of 2 or less on the Clinical Global Impressions-Improvement (CGI-I) between baseline and 1-month follow-up. RESULTS:There was a significant decrease of YBOCS scores between baseline and one-month assessment. At one month, five patients (24%) were considered as responders and 3 (15%) at 3 months. We also observed concomitant changes in depressive symptoms, and insight. The treatment was well tolerated. Short-lasting side effects were reported as localized tingling sensation and skin redness. CONCLUSION:Our results suggest that the use of cathodal tDCS over the SMA and anodal tDCS over the right supraorbital area in OCD treatment-refractory patients is safe and promising to improve obsessive and compulsive symptoms. Large randomized controlled trials are needed to confirm this positive result.
10.1002/brb3.1648
Transcranial direct-current stimulation in ultra-treatment-resistant schizophrenia.
Lindenmayer J P,Kulsa Mila Kirstie C,Sultana Tania,Kaur Amandeep,Yang Ran,Ljuri Isidora,Parker Benedicto,Khan Anzalee
Brain stimulation
BACKGROUND:Transcranial direct-current stimulation (tDCS), a non-invasive neurostimulation treatment, has been reported in a number of sham-controlled studies to show significant improvements in treatment-resistant auditory hallucinations in schizophrenia patients, primarily in ambulatory and higher-functioning patients, but little is known of the effects of tDCS on hospitalized, low-functioning inpatients. OBJECTIVE/HYPOTHESIS:The purpose of this study was to examine the efficacy and safety of tDCS for auditory hallucinations in hospitalized ultra-treatment-resistant schizophrenia (TRS) and to evaluate the effects of tDCS on cognitive functions. We hypothesized that treatment non-response reported in previous tDCS studies may have been due to the insufficient duration of direct-current stimulation. METHODS:Inpatient participants with DSM-V schizophrenia, long-standing treatment-resistance, and auditory verbal hallucinations (AVH) participated in this 4-week sham-controlled, randomized trial. Assessments included the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) at baseline and endpoint (at the end of Week 4), and the Auditory Hallucinations Rating Scale (AHRS) administered at baseline, endpoint, and weekly throughout the study. Participants were randomized to receive active vs. sham tDCS treatments twice daily for 4 weeks. RESULTS:Twenty-eight participants were enrolled (tDCS, n = 15; control, n = 13) and 21 participants completed all 4 weeks of the trial. Results showed a significant reduction for the auditory hallucination total score (p ≤ 0.05). We found a 21.9% decrease in AHRS Total Score for the tDCS group and a 12.6% decrease in AHRS Total Score for the control group. Significant reductions in frequency, number of voices over time, length of auditory hallucinations, and overall psychopathology were also observed for the tDCS group. When assessing cognitive functioning, only Working Memory showed improvement for the tDCS group. CONCLUSION:Although there was only a small improvement noted in auditory hallucination scores for the tDCS group, this improvement was meaningful when compared to no standard treatment of the control group. While this makes the interpretation of clinical significance debatable, it does confirm that tDCS combined with pharmacological intervention can provide clinical gains over pharmacological intervention alone. Therefore, tDCS treatment appears to be effective not only for ambulatory, higher-functioning patients, but also for patients with ultra-treatment-resistant schizophrenia.
10.1016/j.brs.2018.10.002
Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia.
Brunelin Jerome,Mondino Marine,Gassab Leila,Haesebaert Frederic,Gaha Lofti,Suaud-Chagny Marie-Françoise,Saoud Mohamed,Mechri Anwar,Poulet Emmanuel
The American journal of psychiatry
OBJECTIVE:Some 25%–30% of patients with schizophrenia have auditory verbal hallucinations that are refractory to antipsychotic drugs. Outcomes in studies of repetitive transcranial magnetic stimulation suggest the possibility that application of transcranial direct-current stimulation (tDCS) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could affect hallucinations and negative symptoms, respectively. The authors investigated the efficacy of tDCS in reducing the severity of auditory verbal hallucinations as well as negative symptoms. METHOD:Thirty patients with schizophrenia and medication-refractory auditory verbal hallucinations were randomly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays. The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex. RESULTS:Auditory verbal hallucinations were robustly reduced by tDCS relative to sham stimulation, with a mean diminution of 31% (SD=14; d=1.58, 95% CI=0.76–2.40). The beneficial effect on hallucinations lasted for up to 3 months. The authors also observed an amelioration with tDCS of other symptoms as measured by the Positive and Negative Syndrome Scale (d=0.98, 95% CI=0.22–1.73), especially for the negative and positive dimensions. No effect was observed on the dimensions of disorganization or grandiosity/excitement. CONCLUSIONS:Although this study is limited by the small sample size, the results show promise for treating refractory auditory verbal hallucinations and other selected manifestations of schizophrenia.
10.1176/appi.ajp.2012.11071091
Transcranial direct current stimulation: a roadmap for research, from mechanism of action to clinical implementation.
Chase Henry W,Boudewyn Megan A,Carter Cameron S,Phillips Mary L
Molecular psychiatry
Transcranial direct current stimulation (tDCS) is a promising method for altering the function of neural systems, cognition, and behavior. Evidence is emerging that it can also influence psychiatric symptomatology, including major depression and schizophrenia. However, there are many open questions regarding how the method might have such an effect, and uncertainties surrounding its influence on neural activity, and human cognition and functioning. In the present critical review, we identify key priorities for future research into major depression and schizophrenia, including studies of the mechanism(s) of action of tDCS at the neuronal and systems levels, the establishment of the cognitive impact of tDCS, as well as investigations of the potential clinical efficacy of tDCS. We highlight areas of progress in each of these domains, including data that appear to favor an effect of tDCS on neural oscillations rather than spiking, and findings that tDCS administration to the prefrontal cortex during task training may be an effective way to enhance behavioral performance. Finally, we provide suggestions for further empirical study that will elucidate the impact of tDCS on brain and behavior, and may pave the way for efficacious clinical treatments for psychiatric disorders.
10.1038/s41380-019-0499-9