Associations Between GGT/HDL and MAFLD: A Cross-Sectional Study.
Diabetes, metabolic syndrome and obesity : targets and therapy
PURPOSE:To explore the association between γ-glutamyl transpeptidase to high-density lipoprotein ratio (GGT/HDL), triglyceride glucose-body mass index (TYG-BMI), and metabolic associated fatty liver disease (MAFLD) in a Chinese population with type 2 diabetes (T2DM) by cross-sectional analysis. To investigate the role of GGT/HDL played in MAFLD by TYG-BMI. PATIENTS AND METHODS:A total of 1434 adult patients hospitalized with T2DM at Hebei General Hospital (Shijiazhuang, China) were included in the study. Patients' demographic and clinical data were collected. Spearman correlation was used to test for an association between GGT/HDL or TYG-BMI and related risk factors of MAFLD among T2DM patients. Multiple logistic regression analyses were performed to investigate the association between GGT/HDL or TYG-BMI and MAFLD. Mediation analysis was used to explore whether TYG-BMI mediated the association between GGT/HDL and MAFLD. RESULTS:A total of 1434 T2DM patients were enrolled, the MAFLD group showed a higher level of GGT/HDL compared to the non-MAFLD group. There was a progressive increase in the prevalence of MAFLD with increasing tertiles of GGT/HDL. After adjusting for confounding factors, multivariate logistic regression analysis revealed that high levels of GGT/HDL were independent risk factors for MAFLD in T2DM patients. BMI further grouped the patients: ≤ 23kg/m2,>23kg/m2. GGT/HDL was found to be an independent risk factor for MAFLD but only in T2DM patients with a BMI greater than 23 kg/m2. Mediation analysis indicated that GGT/HDL had a significant direct effect on MAFLD. CONCLUSION:GGT/HDL was positively associated with MAFLD incidence in T2DM patients with a BMI greater than 23 Kg/m2, and TYG-BMI partly mediated the association.
10.2147/DMSO.S342505
Association Between Nutrient Patterns and Fatty Liver Index: Baseline Survey of the Japan Multi-Institutional Collaborative Cohort Study in Tokushima, Japan.
Journal of epidemiology
BACKGROUNDS:The fatty liver index (FLI) is a good non-invasive approach for fatty liver disease diagnosis. The objective of this study was to examine the associations of nutrient patterns with non-alcoholic fatty liver disease (NAFLD) in a Japanese population. METHODS:A total of 1,588 subjects (789 men and 799 women) aged 35-69 years were recruited in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima Prefecture. Factor analysis was applied to energy-adjusted intake of 21 nutrients, and nutrient patterns were extracted. Multiple logistic regression analysis was used to analyze the relationships between nutrient patterns and the high FLI category (≥60). RESULTS:Four nutrient patterns were extracted: Factor 1, vitamins, dietary fiber, iron and potassium pattern; Factor 2, fats and fat-soluble vitamins pattern; Factor 3, saturated fat, calcium, vitamin B and low carbohydrate pattern; and Factor 4, sodium, protein and vitamin D pattern. After adjustment for sex, age, and other potential confounding variables, higher Factor 1 scores were significantly associated with lower odds ratios of NAFLD (P for trend <0.05). Analysis of each component of FLI showed that there were significant inverse associations between Factor 1 scores and high body mass index and large waist circumference. CONCLUSION:The present findings suggest that a nutrient pattern rich in vitamins, fiber, iron, and potassium was associated with lower prevalence of NAFLD in a Japanese population. Obesity and abdominal obesity may be intermediate variables for the association between this nutrient pattern and NAFLD.
10.2188/jea.JE20200447
Curcumol inhibits ferritinophagy to restrain hepatocyte senescence through YAP/NCOA4 in non-alcoholic fatty liver disease.
Qi Xiaoyu,Song Anping,Ma Mingyue,Wang Peipei,Zhang Xinbei,Lu Chunfeng,Zhang Junxiu,Zheng Shuguo,Jin Huanhuan
Cell proliferation
OBJECTIVES:In recent years, cellular senescence has attracted a lot of interest in researchers due to its involvement in non-alcoholic fatty liver disease (NAFLD). However, the mechanism of cellular senescence is not clear. The purpose of this study was to investigate the effect of curcumol on hepatocyte senescence in NAFLD and the molecular mechanisms implicated. MATERIALS AND METHODS:LVG Golden Syrian hamsters, C57BL/6J mice and human hepatocyte cell line LO2 were used. Cellular senescence was assessed by analyses of senescence marker SA-β-gal, p16 and p21, H3K9me3, γ-H2AX and telomerase activity. RESULTS:The results showed that curcumol could inhibit hepatocyte senescence in both in vivo and in vitro NAFLD models, and the mechanism might be related to its regulation of ferritinophagy and subsequent alleviation of iron overload. Moreover, overexpression of nuclear receptor coactivator 4 (NCOA4) weakened the effect of curcumol on ferritinophagy-mediated iron overload and cellular senescence. Furthermore, we demonstrated that curcumol reduced the expression of NCOA4 by Yes-associated protein (YAP). In addition, depression of YAP could impair the effect of curcumol on iron overload and cellular senescence. CONCLUSION:Our results clarified the mechanism of curcumol inhibition of hepatocyte senescence through YAP/NCOA4 regulation of ferritinophagy in NAFLD. These findings provided a promising option of curcumol to regulate cellular senescence by target YAP/NCOA4 for the treatment of NAFLD.
10.1111/cpr.13107
PPARα alleviates iron overload-induced ferroptosis in mouse liver.
EMBO reports
Ferroptosis is an iron-dependent form of non-apoptotic cell death implicated in liver, brain, kidney, and heart pathology. How ferroptosis is regulated remains poorly understood. Here, we show that PPARα suppresses ferroptosis by promoting the expression of glutathione peroxidase 4 (Gpx4) and by inhibiting the expression of the plasma iron carrier TRF. PPARα directly induces Gpx4 expression by binding to a PPRE element within intron 3. PPARα knockout mice develop more severe iron accumulation and ferroptosis in the liver when fed a high-iron diet than wild-type mice. Ferrous iron (Fe ) triggers ferroptosis via Fenton reactions and ROS accumulation. We further find that a rhodamine-based "turn-on" fluorescent probe(probe1) is suitable for the in vivo detection of Fe . Probe1 displays high selectivity towards Fe , and exhibits a stable response for Fe with a concentration of 20 μM in tissue. Our data thus show that PPARα activation alleviates iron overload-induced ferroptosis in mouse livers through Gpx4 and TRF, suggesting that PPARα may be a promising therapeutic target for drug discovery in ferroptosis-related tissue injuries. Moreover, we identified a fluorescent probe that specifically labels ferrous ions and can be used to monitor Fe in vivo.
10.15252/embr.202052280
A predictive model for non-completion of an intensive specialist obesity service in a public hospital: a case-control study.
Atlantis Evan,Lin Fang,Anandabaskaran Sulak,Fahey Paul,Kormas Nic
BMC health services research
BACKGROUND:Despite the growing evidence base supporting intensive lifestyle and medical treatments for severe obesity, patient engagement in specialist obesity services is difficult to achieve and poorly understood. To address this knowledge gap, we aimed to develop a model for predicting non-completion of a specialist multidisciplinary service for clinically severe obesity, termed the Metabolic Rehabilitation Programme (MRP). METHOD:Using a case-control study design in a public hospital setting, we extracted data from medical records for all eligible patients with a body mass index (BMI) of ≥35 kg/m with either type 2 diabetes or fatty liver disease referred to the MRP from 2010 through 2015. Non-completion status (case definition) was coded for patients whom started but dropped-out of the MRP within 12 months. Using multivariable logistic regression, we tested the following baseline predictors hypothesised in previous research: age, gender, BMI, waist circumference, residential distance from the clinic, blood pressure, obstructive sleep apnoea (OSA), current continuous positive airway pressure (CPAP) therapy, current depression/anxiety, diabetes status, and medications. We used receiver operating characteristics and area under the curve to test the performance of models. RESULTS:Out of the 219 eligible patient records, 78 (35.6%) non-completion cases were identified. Significant differences between non-completers versus completers were: age (47.1 versus 54.5 years, p < 0.001); residential distance from the clinic (21.8 versus 17.1 km, p = 0.018); obstructive sleep apnoea (OSA) (42.9% versus 56.7%, p = 0.050) and CPAP therapy (11.7% versus 28.4%, p = 0.005). The probability of non-completion could be independently associated with age, residential distance, and either OSA or CPAP. There was no statistically significant difference in performance between the alternate models (69.5% versus 66.4%, p = 0.57). CONCLUSIONS:Non-completion of intensive specialist obesity management services is most common among younger patients, with fewer complex care needs, and those living further away from the clinic. Clinicians should be aware of these potential risk factors for dropping out early when managing outpatients with severe obesity, whereas policy makers might consider strategies for increasing access to specialist obesity management services.
10.1186/s12913-019-4531-1
The burden of nonalcoholic steatohepatitis (NASH) in the United States.
BMC gastroenterology
BACKGROUND:There is limited data on the comparative economic and humanistic burden of non-alcoholic steatohepatitis (NASH) in the United States. The objective was to examine the burden of disease comparing NASH to a representative sample of the general population and separately to a type 2 diabetes mellitus (T2DM) cohort by assessing health-related quality of life (HRQoL) measures, healthcare resource use (HRU) and work productivity and activity impairment (WPAI). METHODS:Data came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey conducted in the United States. Respondents with physician-diagnosed NASH, physician-diagnosed T2DM, and respondents from the general population were compared. Humanistic burden was examined with mental (MCS) and physical (PCS) component summary scores from the Short-Form (SF)-36v2, concomitant diagnosis of anxiety, depression, and sleep difficulties. Economic burden was analysed based on healthcare professional (HCP) and emergency room (ER) visits, hospitalizations in the past six months; absenteeism, presenteeism, overall work impairment, and activity impairment scores on WPAI questionnaire. Bivariate and multivariable analysis were conducted for each outcome and matched comparative group. RESULTS:After adjusting for baseline demographics and characteristics, NASH (N = 136) compared to the matched general population cohort (N = 544), reported significantly lower (worse) mental (MCS 43.19 vs. 46.22, p = 0.010) and physical (PCS 42.04 vs. 47.10, p < 0.001) status, higher % with anxiety (37.5% vs 25.5%, p = 0.006) and depression (43.4% vs 30.1%, p = 0.004), more HCP visits (8.43 vs. 5.17), ER visits (0.73 vs. 0.38), and hospitalizations (0.43 vs. 0.2) all p's < 0.05, and higher WPAI scores (e.g. overall work impairment 39.64% vs. 26.19%, p = 0.011). NASH cohort did not differ from matched T2DM cohort (N = 272) on mental or work-related WPAI scores, but had significantly worse physical status (PCS 40.52 vs. 44.58, p = 0.001), higher % with anxiety (39.9% vs 27.8%, p = 0.043), more HCP visits (8.63 vs. 5.68, p = 0.003) and greater activity impairment (47.14% vs. 36.07%, p = 0.010). CONCLUSION:This real-world study suggests that burden of disease is higher for all outcomes assessed among NASH compared to matched general controls. When comparing to T2DM, NASH cohort has comparable mental and work-related impairment but worse physical status, daily activities impairment and more HRU.
10.1186/s12876-023-02726-2
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
The impact of fatigue on mortality of patients with non-alcoholic fatty liver disease: Data from National Health and nutrition examination survey 2005-2010 and 2017-2018.
Liver international : official journal of the International Association for the Study of the Liver
OBJECTIVE:Fatigue among patients with NAFLD may negatively impact their health-related quality of life and clinical outcomes (mortality). We determined fatigue prevalence and its association with all-cause mortality among patients with NAFLD. DESIGN:NHANES 2005-2010 and 2017-2018 data were used with linked mortality data. NAFLD was defined by fatty liver index for NHANES 2005-2010 and by transient elastography for NHANES 2017-2018. Fatigue was assessed by Patient Health Questionnaire. RESULTS:NHANES 2005-2010 cohort (n = 5429, mean age 47.1 years, 49.7% male, 69.9% white), 37.6% had NAFLD. Compared to non-NAFLD controls, fatigue was more common in NAFLD (8.35% vs 6.0%, p = .002). Among NHANES 2017-2018 cohort (n = 3830, mean age 48.3 years, 48.6% male, 62.3% white), 36.9% had NAFLD. Compared to non-NAFLD controls, fatigue was more common among NAFLD (8.7% vs 6.2%). NAFLD had more sleep disturbance (34.0% vs 26.7%), cardiovascular disease (CVD) (10.7% vs. 6.3%), significant hepatic fibrosis (liver stiffness>8.0 kPa, 17.9% vs 3.5%) and advanced hepatic fibrosis (>13.1 kPa, 5.4% vs 0.9%; all p < .003). The presence of depression (OR: 11.52, 95% CI: 4.45-29.80, p < .0001), CVD (OR: 3.41, 95% CI: 1.02-11.34, p = .0462) and sleep disturbance (OR: 2.00, 95% CI: 1.00-3.98, p = .0491) was independently associated with fatigue; good sleep quality (OR: 0.58, 95% CI: 0.35-0.96, p = .0366) had an inverse association. By multivariable Cox model, NAFLD adults with fatigue experienced 2.3-fold higher mortality than NAFLD without fatigue (HR: 2.31, 95% CI: 1.37-3.89, p = .002). CONCLUSIONS:Fatigue among those with NAFLD is associated with increased risk for mortality and is mainly driven by depression, sleep disturbance and CVD. These findings have important clinical implications.
10.1111/liv.15437
Complications of Non-Alcoholic Fatty Liver Disease in Extrahepatic Organs.
Tomeno Wataru,Imajo Kento,Takayanagi Takuya,Ebisawa Yu,Seita Kosuke,Takimoto Tsuneyuki,Honda Kanami,Kobayashi Takashi,Nogami Asako,Kato Takayuki,Honda Yasushi,Kessoku Takaomi,Ogawa Yuji,Kirikoshi Hiroyuki,Sakamoto Yasunari,Yoneda Masato,Saito Satoru,Nakajima Atsushi
Diagnostics (Basel, Switzerland)
Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most common chronic liver disease worldwide, along with the concurrent epidemics of metabolic syndrome and obesity. Patients with NAFLD have increased risks of end-stage liver disease, hepatocellular carcinoma, and liver-related mortality. However, the largest cause of death among patients with NAFLD is cardiovascular disease followed by extrahepatic malignancies, whereas liver-related mortality is only the third cause of death. Extrahepatic complications of NAFLD include chronic kidney disease, extrahepatic malignancies (such as colorectal cancer), psychological dysfunction, gastroesophageal reflux disease, obstructive sleep apnea syndrome, periodontitis, hypothyroidism, growth hormone deficiency, and polycystic ovarian syndrome. The objective of this narrative review was to summarize recent evidences about extrahepatic complications of NAFLD, with focus on the prevalent/incident risk of such diseases in patients with NAFLD. To date, an appropriate screening method for extrahepatic complications has not yet been determined. Collaborative care with respective experts seems to be necessary for patient management because extrahepatic complications can occur across multiple organs. Further studies are needed to reveal risk profiles at baseline and to determine an appropriate screening method for extrahepatic diseases.
10.3390/diagnostics10110912
Child and adolescent obesity.
Nature reviews. Disease primers
The prevalence of child and adolescent obesity has plateaued at high levels in most high-income countries and is increasing in many low-income and middle-income countries. Obesity arises when a mix of genetic and epigenetic factors, behavioural risk patterns and broader environmental and sociocultural influences affect the two body weight regulation systems: energy homeostasis, including leptin and gastrointestinal tract signals, operating predominantly at an unconscious level, and cognitive-emotional control that is regulated by higher brain centres, operating at a conscious level. Health-related quality of life is reduced in those with obesity. Comorbidities of obesity, including type 2 diabetes mellitus, fatty liver disease and depression, are more likely in adolescents and in those with severe obesity. Treatment incorporates a respectful, stigma-free and family-based approach involving multiple components, and addresses dietary, physical activity, sedentary and sleep behaviours. In adolescents in particular, adjunctive therapies can be valuable, such as more intensive dietary therapies, pharmacotherapy and bariatric surgery. Prevention of obesity requires a whole-system approach and joined-up policy initiatives across government departments. Development and implementation of interventions to prevent paediatric obesity in children should focus on interventions that are feasible, effective and likely to reduce gaps in health inequalities.
10.1038/s41572-023-00435-4
Metabolic syndrome in bipolar disorder: a review with a focus on bipolar depression.
McElroy Susan L,Keck Paul E
The Journal of clinical psychiatry
OBJECTIVE:To perform a detailed, qualitative review of existing literature on the co-occurrence of bipolar disorder and metabolic syndrome, the impact of metabolic dysregulation on patients with bipolar disorder, and treatment considerations, with a focus on bipolar depression. DATA SOURCES:Searches of the PubMed database (October 23, 2012) and Cochrane Library (September 20, 2013) were conducted for English-language articles published from January 1980 onward containing the keywords bipolar AND metabolic, weight, obesity, diabetes, dyslipidemia, OR hypertension in the title or abstract. The searches yielded 1,817 citations from which case reports, conference abstracts, and pediatric studies were excluded. STUDY SELECTION:Abstracts and titles were evaluated for relevance to the stated objectives. Full texts of 176 articles were obtained for further evaluation; additional articles were identified from reference lists. RESULTS:Metabolic risk factors are highly prevalent yet undertreated in patients with bipolar disorder. Putative factors accounting for the link between bipolar disorder and metabolic syndrome include behavioral/phenomenological features, shared neurobiologic abnormalities, and adverse effects of psychotropic medications. A comprehensive assessment of metabolic risk and regular monitoring of body mass index, waist circumference, lipid profile, and plasma glucose are important for patients with bipolar disorder. Management strategies for the bipolar patient with metabolic risk factors include use of bipolar disorder medications with better metabolic profiles, lifestyle interventions, and adjunctive pharmacotherapy for dyslipidemia, hypertension, and/or hyperglycemia. CONCLUSIONS:Adequate management of metabolic syndrome may improve clinical outcomes in patients with bipolar disorder, as well as prevent adverse cardiovascular events and the development of diabetes.
10.4088/JCP.13r08634
Depression and 24 gastrointestinal diseases: a Mendelian randomization study.
Translational psychiatry
The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.
10.1038/s41398-023-02459-6
Non-alcoholic fatty liver disease - A global public health perspective.
Younossi Zobair M
Journal of hepatology
As the epidemics of obesity and type 2 diabetes mellitus increase worldwide, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing proportionately. The subtype of NAFLD which can be characterised as non-alcoholic steatohepatitis (NASH) is a potentially progressive liver disease that can lead to cirrhosis, hepatocellular carcinoma, liver transplantation, and death. NAFLD is also associated with extrahepatic manifestations such as chronic kidney disease, cardiovascular disease and sleep apnoea. NAFLD and NASH carry a large economic burden and create poor health-related quality of life. Despite this important burden, we are only beginning to understand its mechanisms of pathogenesis and the contribution of environmental and genetic factors to the risk of developing a progressive course of disease. Research is underway to identify appropriate non-invasive diagnostic methods and effective treatments. Although the risk of liver-related mortality is increased in patients with NAFLD and liver fibrosis stages F3 or F4, the leading cause of death is cardiovascular disease. Given the rapidly growing global burden of NAFLD and NASH, efforts must continue to find accurate non-invasive diagnostic and prognostic biomarkers, to develop effective treatments for individuals with advanced NASH and prevention methods for individuals at high risk of NAFLD and progressive liver disease.
10.1016/j.jhep.2018.10.033
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
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
The burden of non-alcoholic steatohepatitis (NASH) among patients from Europe: A real-world patient-reported outcomes study.
JHEP reports : innovation in hepatology
Data on the economic and humanistic burden of non-alcoholic steatohepatitis (NASH) are scarce. This study assessed the comparative burden of NASH, relative to a representative sample from the general population and a type 2 diabetes mellitus (T2DM) cohort, in terms of health-related quality of life, work productivity and activity impairment (WPAI), and healthcare resource use. METHODS:Data across 5 European countries came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey. Outcomes included mental (MCS) and physical (PCS) component scores from the Short-Form (SF)-36v2, WPAI scores, self-reported physician diagnosis of sleep difficulties, anxiety, and depression, and healthcare resource use: healthcare professional visits, hospital visits, and emergency room visits in the previous 6 months. Bivariate and multivariable analyses were conducted for each outcome and comparative group. RESULTS:After adjusting for matching criteria and covariates, patients with NASH (n = 184) reported significantly worse health-related quality of life, worse WPAI scores, and more healthcare resource use than the general population (n = 736) (MCS 39.22 45.16, PCS 42.84 47.76; overall work impairment 49.15% 30.77%, healthcare professional visits 10.73 6.01, emergency room visits 0.57 0.22, hospitalizations 0.47 0.17, ≪0.05 for all). Patients with NASH did not differ from patients with T2DM (n = 368) on PCS and WPAI scores, suggesting a similar impairment on work and daily activities, but did report significantly worse mental status (MCS 39.64 43.64, ≪0.05) and more healthcare resource use than those with T2DM (healthcare professional visits 10.85 7.86, emergency room visits 0.65 0.23, hospitalizations 0.39 0.19, ≪0.05 for all). CONCLUSIONS:These findings suggest that the burden of NASH may be underestimated, highlighting the unmet needs of patients with NASH. LAY SUMMARY:These findings show that patients with non-alcoholic steatohepatitis (NASH) experience a significant burden of illness, in terms of health-related quality of life, work productivity and activity impairment, and healthcare resource use. As there is currently no approved treatment for NASH, these findings highlight the unmet medical need of patients with NASH.
10.1016/j.jhepr.2019.05.009
The burden of non-alcoholic steatohepatitis: A systematic review of health-related quality of life and patient-reported outcomes.
JHEP reports : innovation in hepatology
Background & Aims:Non-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients' health-related quality of life (HRQoL), but published data on the humanistic burden of disease are limited. This review aimed to summarise and critically evaluate studies reporting HRQoL or patient-reported outcomes (PROs) in populations with NASH and identify key gaps for further research. Methods:Medline, EMBASE, the Cochrane Library and PsycINFO were searched for English-language publications published from 2010 to 2021 that reported HRQoL/PRO outcomes of a population or subpopulation with NASH. Results:Twenty-five publications covering 23 unique studies were identified. Overall, the data showed a substantial impact of NASH on HRQoL, particularly in terms of physical functioning and fatigue, with deterioration of physical and mental health as NASH progresses. Prevalent symptoms, including fatigue, abdominal pain, anxiety/depression, cognition problems, and poor sleep quality, adversely impact patients' ability to work and perform activities of daily living and the quality of relationships. However, some patients fail to attribute symptoms to their disease because of a lack of patient awareness and education. NASH is associated with high rates of comorbidities such as obesity and type 2 diabetes, which contribute to reduced HRQoL. Studies were heterogeneous in terms of diagnostic methods, population, outcomes, follow-up time, and measures of HRQoL/utility. Most studies were rated 'moderate' at quality assessment, and all evaluable studies had inadequate control of confounders. Conclusions:NASH is associated with a significant HRQoL burden that begins early in the disease course and increases with disease progression. More robust studies are needed to better understand the humanistic burden of NASH, with adequate adjustment for confounders that could influence outcomes. Lay summary:Non-alcoholic steatohepatitis (NASH) has a significant impact on quality of life, with individuals experiencing worse physical and mental health compared with the general population. NASH and its symptoms, which include tiredness, stomach pain, anxiety, depression, poor focus and memory, and impaired sleep, affect individuals' relationships and ability to work and perform day-to-day tasks. However, not all patients are aware that their symptoms may be related to NASH. Patients would benefit from more education on their disease, and the importance of good social networks for patient health and well-being should be reinforced. More studies are needed to better understand the patient burden of NASH.
10.1016/j.jhepr.2022.100525
Elevated alanine aminotransferase independently predicts new onset of depression in employees undergoing health screening examinations.
Zelber-Sagi S,Toker S,Armon G,Melamed S,Berliner S,Shapira I,Halpern Z,Santo E,Shibolet O
Psychological medicine
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression. METHOD:The present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score. RESULTS:The final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40-2.92] and major (OR 3.132, 95% CI 1.81-5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001). CONCLUSIONS:Elevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression.
10.1017/S0033291713000500
Tlr4 upregulation in the brain accompanies depression- and anxiety-like behaviors induced by a high-cholesterol diet.
Strekalova Tatyana,Evans Matthew,Costa-Nunes Joao,Bachurin Sergey,Yeritsyan Naira,Couch Yvonne,Steinbusch Harry M W,Eleonore Köhler S,Lesch Klaus-Peter,Anthony Daniel C
Brain, behavior, and immunity
An association between metabolic abnormalities, hypercholesterolemia and affective disorders is now well recognized. Less well understood are the molecular mechanisms, both in brain and in the periphery, that underpin this phenomenon. In addition to hepatic lipid accumulation and inflammation, C57BL/6J mice fed a high-cholesterol diet (0.2%) to induce non-alcoholic fatty liver disease (NAFLD), exhibited behavioral despair, anxiogenic changes, and hyperlocomotion under bright light. These abnormalities were accompanied by increased expression of transcript and protein for Toll-like receptor 4, a pathogen-associated molecular pattern (PAMP) receptor, in the prefrontal cortex and the liver. The behavioral changes and Tlr4 expression were reversed ten days after discontinuation of the high-cholesterol diet. Remarkably, the dietary fat content and body mass of experimental mice were unchanged, suggesting a specific role for cholesterol in the molecular and behavioral changes. Expression of Sert and Cox1 were unaltered. Together, our study has demonstrated for the first time that high consumption of cholesterol results in depression- and anxiety-like changes in C57BL/6J mice and that these changes are unexpectedly associated with the increased expression of TLR4, which suggests that TLR4 may have a distinct role in the CNS unrelated to pathogen recognition.
10.1016/j.bbi.2015.02.015
Sex differences in the relationship between hepatic steatosis, mood and anxiety disorders.
Journal of psychosomatic research
OBJECTIVE:To investigate the association between non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), mental symptoms (mood, anxiety disorders and distress) by sex. METHODS:This a cross-sectional study performed in working-age adults from a Health Promotion Center (primary care) in São Paulo, Brazil. Self-reported mental symptoms from rating scales (21-item Beck Anxiety Inventory, Patient Health Questionnaire-9, and K6 distress scale) were evaluated by hepatic steatosis (NAFLD and ALD). Logistic regression models estimated the association between hepatic steatosis subtypes and mental symptoms by Odds ratios (OR) adjusted by confounders in the total sample and sex stratified. RESULTS:Among 7241 participants (70.5% men, median age: 45 years), the frequency of steatosis was of 30.7% (25.1% NAFLD), being higher in men than women (70.5% vs. 29.5%, p < 0.0001), regardless of the steatosis subtype. Metabolic risk factors were similar in both subtypes of steatosis, but not mental symptoms. Overall, NAFLD was inversely associated with anxiety (OR = 0.75, 95%CI 0.63-0.90) and positively associated with depression (OR = 1.17, 95%CI 1.00-1.38). On the other hand, ALD was positively associated with anxiety (OR = 1.51; 95%CI 1.15-2.00). In sex-stratified analyses, only men presented an association of anxiety symptoms with NAFLD (OR = 0.73; 95%CI 0.60-0.89) and ALD (OR = 1.60; 95%CI 1.18-2.16). CONCLUSIONS:The complex association between different types of steatosis (NAFLD and ALD), mood and anxiety disorders indicates the need for a deeper understanding of their common causal pathways.
10.1016/j.jpsychores.2023.111216
The prevalence and burden of Rome IV bowel disorders of gut brain interaction in patients with non-alcoholic fatty liver disease: a cross-sectional study.
Scientific reports
Rome IV bowel disorders of gut brain interaction (DGBI) and non-alcoholic fatty liver disease (NAFLD) are highly prevalent entities with overlapping pathophysiology and risk factors. We aimed to evaluate the prevalence and burden of Rome IV irritable bowel syndrome (IBS) in patients with NAFLD. Patients diagnosed with NAFLD were recruited from a specialist liver clinic. All participants completed assessments to determine liver fibrosis severity, including liver stiffness measurement (LSM), completed the Rome IV diagnostic questionnaire for bowel disorders of gut brain interaction, the IBS symptom severity score (IBS-SSS), and the EQ-5D-5L to measure of quality-of-life (QoL). 142 patients with NAFLD (71 (50%) female, mean age 53.5 (SD ± 14.9), BMI 35.2 (SD ± 8.1) kg/M) were recruited. 79 (55.6%) patients met criteria for a Rome IV bowel DGBI, including 50 patients (35.2%) who met the criteria for IBS (mean IBS-SSS 277.2 (SD ± 131.5)). There was no difference in liver fibrosis scores between those with and without Rome IV IBS (FIB-4 scores p = 0.14, LSM p = 0.68). Patients with NAFLD and Rome IV IBS had significantly worse QoL scores (EQ-VAS p = 0.005 and EQ-5D-5L index p = 0.0007), impairment of usual activities of daily living (p = 0.012) and were more likely to report anxiety or depression (p = 0.038). Rome IV bowel DGBI such as IBS are highly prevalent in patients with NAFLD attending liver clinics and are associated with impaired QoL and psychosocial distress.
10.1038/s41598-023-35774-5
The antipsychotic drug olanzapine altered lipid metabolism in the common carp (Cyprinus carpio L.): Insight from the gut microbiota-SCFAs-liver axis.
The Science of the total environment
Olanzapine (OLA) is a common drug used to treat schizophrenia and has recently come under increasing scrutiny as an emerging contaminant. However, its impact on lipid metabolism in fish and its mechanisms of action are not well understood. In this study, common carp were exposed to 0, 10, 100, and 250 μM OLA for 60 days. The results indicated that OLA exposure increased weight gain, total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG) and decreased high-density lipoprotein (HDL). In addition, lipids accumulated in the liver of the common carp. To explore the underlying mechanisms of action, gut microbiota, short-chain fatty acids (SCFAs), liver transcripts, and genes related to lipid metabolism were measured. It was discovered that OLA exposure altered the common carp gut microbiota composition and increased the abundance of SCFA-producing bacteria. Correspondingly, this study showed that OLA exposure increased the levels of SCFAs, which are highly relevant to the development of lipid accumulation. Transcriptome sequencing results indicated that OLA exposure could change lipid metabolism signalling pathways, including steroid biosynthesis, the PPAR signalling pathway, asglycerophospholipid metabolism, glycerolipid metabolism, and fatty acid metabolic pathways of the common carp. Additionally, OLA exposure interrupted lipid metabolism by means of significant upregulation of lipid synthesis-related genes, including pparγ, srebp1, and fas. OLA exposure also resulted in significant lipolysis-related gene downregulation, including cpt, lpl, hsl, and pparα. The results of this study indicated that contamination of aquatic environments with OLA alters lipid metabolism in common carp. In addition, the underlying mechanism might be due in part to the modulation of the gut microbiota-SCFA-PPAR signalling pathway.
10.1016/j.scitotenv.2022.159054
Key role for lipids in cognitive symptoms of schizophrenia.
Maas Dorien A,Martens Marijn B,Priovoulos Nikos,Zuure Wieteke A,Homberg Judith R,Nait-Oumesmar Brahim,Martens Gerard J M
Translational psychiatry
Schizophrenia (SZ) is a psychiatric disorder with a convoluted etiology that includes cognitive symptoms, which arise from among others a dysfunctional dorsolateral prefrontal cortex (dlPFC). In our search for the molecular underpinnings of the cognitive deficits in SZ, we here performed RNA sequencing of gray matter from the dlPFC of SZ patients and controls. We found that the differentially expressed RNAs were enriched for mRNAs involved in the Liver X Receptor/Retinoid X Receptor (LXR/RXR) lipid metabolism pathway. Components of the LXR/RXR pathway were upregulated in gray matter but not in white matter of SZ dlPFC. Intriguingly, an analysis for shared genetic etiology, using two SZ genome-wide association studies (GWASs) and GWAS data for 514 metabolites, revealed genetic overlap between SZ and acylcarnitines, VLDL lipids, and fatty acid metabolites, which are all linked to the LXR/RXR signaling pathway. Furthermore, analysis of structural T-weighted magnetic resonance imaging in combination with cognitive behavioral data showed that the lipid content of dlPFC gray matter is lower in SZ patients than in controls and correlates with a tendency towards reduced accuracy in the dlPFC-dependent task-switching test. We conclude that aberrations in LXR/RXR-regulated lipid metabolism lead to a decreased lipid content in SZ dlPFC that correlates with reduced cognitive performance.
10.1038/s41398-020-01084-x
Dietary patterns and risk of non-alcoholic fatty liver disease in adults: A prospective cohort study.
Zhang Shunming,Gu Yeqing,Bian Shanshan,Górska Magdalena J,Zhang Qing,Liu Li,Meng Ge,Yao Zhanxin,Wu Hongmei,Wang Yawen,Zhang Tingjing,Wang Xuena,Sun Shaomei,Wang Xing,Zhou Ming,Jia Qiyu,Song Kun,Qi Lu,Niu Kaijun
Clinical nutrition (Edinburgh, Scotland)
BACKGROUND AND AIMS:Prospective cohort studies linking dietary patterns and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between dietary patterns and risk of NAFLD in a general Chinese adult population. METHODS:This study included a total of 17,360 participants free from NAFLD at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated 100-item food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between dietary patterns and risk of NAFLD. RESULTS:During a median follow-up of 4.2 years, 4034 NAFLD cases were documented. Three main dietary patterns were extracted: sugar rich dietary pattern, vegetable rich dietary pattern, and animal food dietary pattern. After adjusting for age, sex, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, depressive symptoms, dietary supplement use, inflammation markers, and each other dietary pattern score, comparing the highest with the lowest quartiles of dietary pattern scores, the multivariable hazard ratios (95% confidence interval) of NAFLD were 1.11 (1.01, 1.23) for sugar rich dietary pattern, 0.96 (0.86, 1.07) for vegetable rich dietary pattern, and 1.22 (1.10, 1.36) for animal food dietary pattern. Further adjustment for waist circumference instead of body mass index provided similar results. CONCLUSION:Dietary patterns rich in animal foods or sugar were associated with a higher risk of NAFLD among Chinese adults, whereas a vegetable rich dietary pattern was not associated.
10.1016/j.clnu.2021.08.021
Association between depression and nonalcoholic fatty liver disease: Contributions of insulin resistance and inflammation.
Lee Ju Won,Park Seung Ha
Journal of affective disorders
BACKGROUND:It is unclear whether depression is linked to nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to examine the association between depression and NAFLD and whether the association is partly explained by insulin resistance or inflammation. METHODS:Subjects consisted of 4,688 adults who participated in the 2016 Korea National Health and Nutrition Examination Survey. Depression was defined by Patient Health Questionnaire-9 score ≥ 10 or a previous diagnosis of depression. NAFLD was defined by hepatic steatosis index >36. Insulin resistance was assessed by triglycerides and glucose (TyG) index. Inflammation was measured with C-reactive protein (CRP). RESULTS:Depression had a significant association with TyG index (p = 0.005), but not with CRP. Depression was a significant predictor of NAFLD (OR = 1.63; 95% CI, 1.26-2.10; p < 0.001). Adjustment for sociodemographic features and waist circumference did not substantially affect the results. Further adjustment for comorbidities reduced the estimate for depression by 23% (OR = 1.56; 95% CI, 1.18-2.06; p = 0.002). Inclusion of CRP in a fully adjusted model did not affect the results. Addition of the TyG index decreased the estimate for depression by 28% (OR = 1.39; 95% CI, 0.88-2.19; p = 0.161), and the resulting estimate became no longer significant. The TyG index remained the independent predictor of outcome. LIMITATIONS:The absence of a structured diagnostic interview for depression and histological diagnosis of NAFLD. CONCLUSIONS:These data support an association of depression with NAFLD. Insulin resistance seems to play a major role in modulating the association between depression and NAFLD risk.
10.1016/j.jad.2020.09.073
Association between bedtime at night and nonalcoholic fatty liver disease diagnosed by liver ultrasound transient elastography.
Diabetes research and clinical practice
OBJECTIVE:We aimed to explore the association between bedtime at night and nonalcoholic fatty liver disease (NAFLD) measured by liver ultrasound transient elastography (LUTE). METHODS:A total of 4572 individuals were included. The diagnosis of NAFLD was based on the controlled attenuated parameter (CAP) score of LUTE. CAP score ≥ 263 dB/m and CAP score ≥ 285 dB/m were used as the criterions for the diagnosis of NAFLD. RESULTS:For the weekday bedtime, a positive association was identified in CAP (263 dB/m) (OR, 1.04 [95 %CI, 0.99, 1.09]) and CAP (285 dB/m) (OR, 1.00 [95 %CI, 0.95, 1.05]). For the weekend bedtime, a positive relationship was found in CAP (263 dB/m) (OR, 1.05 [95 %CI, 1.00, 1.10]). The positive relationship still presented in CAP (285 dB/m) (OR, 1.05[95 %CI, 1.00, 1.10]). When NAFLD defined as CAP score ≥ 263 dB/m, the relationship between weekday bedtime and NAFLD was a straight line. For the weekend bedtime, the association was nonlinear. Before 22:00 o'clock, the association was positive (OR, 1.26 [95 %CI, 1.06, 1.50]), while between 22:00 and 1:00 o'clock, the relationship was negative (OR, 0.96 [95 %CI, 0.88, 1.05]) without a significant P value. After 1:00o'clock, the relationship was positive (OR, 1.26 [95 %CI, 1.02, 1.57]). CONCLUSION:Later bedtime was positive associated with NAFLD.
10.1016/j.diabres.2022.109195
Association between self-reported snoring and metabolic-associated fatty liver disease: A cross-sectional analysis of the NHANES 2017-2018.
Sleep medicine
BACKGROUND:Snoring may play an important role in a variety of diseases, especially metabolic diseases. However, there are no reports on the relationship between snoring and the risk of metabolic-associated fatty liver disease (MAFLD). This study aimed to investigate the association between snoring and MAFLD. METHODS:A cross-sectional analysis was performed based on the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Self-reported snoring frequency was grouped into four categories (never, rarely, occasionally, and frequently). MAFLD was diagnosed based on the evidence of hepatic steatosis and any of the following three conditions: overweight/obesity, diabetes mellitus or metabolic dysfunction. Logistic regression with sampling weights was used to examine the association between snoring and MAFLD. RESULTS:A total of 5016 patients were included, and 50.14% of individuals had MAFLD. Compared with nonsnorers, those who snored frequently were associated with increased odds for MAFLD (odds ratio (OR): 1.376, 95% confidence interval (CI): 1.122-1.688, p trend <0.001). The subgroup analyses suggested that no significant interactions were found between snoring and other potential effect modifiers, including age, sex, body mass index (BMI), smoking status, chronic obstructive pulmonary disease (COPD) and hypertension. CONCLUSION:Snoring was independently and positively associated with a higher prevalence of MAFLD, suggesting that attention to snoring may contribute to the early detection of MAFLD.
10.1016/j.sleep.2022.11.029
Association of waist-calf circumference ratio, waist circumference, calf circumference, and body mass index with all-cause and cause-specific mortality in older adults: a cohort study.
BMC public health
BACKGROUND:Waist circumference (WC), calf circumference (CC), and body mass index (BMI) have been independently linked to mortality. However, it's not yet clear how the waist-calf circumference ratio (WCR) relates to mortality. This study aims to investigate the relationship between WCR, WC, CC, and BMI with all-cause and cause-specific mortality in older adults. METHODS:In the 2014 Chinese Longitudinal Healthy Longevity Survey, 4627 participants aged 65 years and older were included, and they were subsequently followed up in 2018. Cox proportional hazards models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality, based on WCR, WC, CC, and BMI. RESULTS:During a median follow-up of 3.4 years, 1671 deaths (36.1%) occurred. Compared to the second quartile of WCR, the highest quartile had a higher risk of mortality from all causes (HR 1.42, 95%CI 1.24-1.64), cardiovascular disease (CVD) (HR 1.88, 95%CI 1.38-2.56), and other causes (HR 1.37, 95%CI 1.15-1.63). The first and fourth quartiles of WC had HRs of 2.19 (1.00-4.79) and 2.69 (1.23-5.89), respectively, for cancer mortality. The highest quartile of CC was associated with a lower risk of all-cause and other-cause mortality, whereas the lowest quartile was associated with a higher risk of all-cause, CVD, and other-cause mortality compared to the second CC quartile. Additionally, the lowest quartile of BMI was associated with a higher risk of all-cause and respiratory disease mortality. Interaction analyses showed that the effects of CC on all-cause and CVD mortality were more pronounced in adults aged ≥ 80 years (P-interaction < .05). CONCLUSIONS:Higher WCR and lower CC increased the risk of all-cause, CVD, and other-cause mortality. Lower BMI was associated with higher all-cause and respiratory disease mortality risk, while WC only predicted cancer mortality.
10.1186/s12889-023-16711-7
Metabolic syndrome in a French cohort of patients with bipolar disorder: results from the FACE-BD cohort.
Godin Ophélia,Etain Bruno,Henry Chantal,Bougerol Thierry,Courtet Philippe,Mayliss Leroux,Passerieux Christine,Azorin Jean-Michel,Kahn Jean-Pierre,Gard Sebastien,Costagliola Dominique,Leboyer Marion,
The Journal of clinical psychiatry
OBJECTIVE:The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with bipolar disorder; determine correlations with sociodemographic, clinical, and treatment-related factors; and investigate the gap between optimal care and effective care of the treated patients. METHOD:654 bipolar disorder patients from the FACE-BD cohort were included from 2009 to 2012. Sociodemographic and clinical characteristics, lifestyle information, and data on antipsychotic treatment and comorbidities were collected, and a blood sample was drawn. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis of bipolar disorder. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS:18.5% of individuals with bipolar disorder met criteria for MetS. Two-thirds of bipolar disorder patients did not receive adequate treatment for MetS components. Multivariate analysis showed that risk of MetS in men was nearly twice that in women (OR = 1.9; 95% CI, 1.0-3.8), and older patients had a 3.5 times higher risk (95% CI, 1.5-7.8) of developing MetS than patients under the age of 35 years. Moreover, patients receiving antipsychotic treatment had a 2.3 times increased risk (95% CI, 1.2-3.5) of having MetS, independent of other potential confounders. CONCLUSIONS:The prevalence of MetS is high in bipolar disorder patients, and there was considerable undertreatment of the components of MetS in this population. The prevention and treatment of cardiovascular diseases in these patients should be assessed systematically. The findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers.
10.4088/JCP.14m09038
Lurasidone and risk of metabolic syndrome: results from short and long-term studies in patients with bipolar depression.
CNS spectrums
OBJECTIVE:The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression. METHODS:Data used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N = 1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N = 316; adjunctive therapy, N = 497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N = 490). MetS was defined based on NCEP ATP III criteria (2005 revision). RESULTS:The proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28 weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group. CONCLUSIONS:This post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.
10.1017/S1092852923001190
Prevalence of and risk factors for non-alcoholic fatty liver disease in a Chinese population: An 8-year follow-up study.
Lu Zhen-Ya,Shao Zhou,Li Ya-Li,Wulasihan Muhuyati,Chen Xin-Hua
World journal of gastroenterology
AIM:To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease (NAFLD) in a Chinese population. METHODS:A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD. RESULTS:A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greater increase in body mass index (BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase. CONCLUSION:NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels.
10.3748/wjg.v22.i13.3663
Comparison of the diagnostic value between triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio in metabolic-associated fatty liver disease patients: a retrospective cross-sectional study.
Lipids in health and disease
BACKGROUND:The triglyceride and glucose index (TyG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute markers of insulin resistance (IR). In a retrospective cross-sectional study, the authors aimed to compare the efficacy of the two indicators in diagnosing metabolic-associated fatty liver disease (MAFLD) to construct a novel disease diagnosis model. METHODS:Overall, 229 patients (97 MAFLD and 132 Non-MAFLD at West China Hospital of Sichuan University were included. MAFLD was diagnosed using ultrasonography. Biochemical indexes were collected and analyzed by logistic regression to screen out indicators that were expressed differently in MAFLD patients and healthy controls, which were incorporated into a diagnostic model. RESULTS:After adjusting for age, sex, and body mass index (BMI), serum alanine transaminase (ALT), aspartate transaminase (AST), AST/ALT (A/A), fasting plasma glucose (FPG), cystatin C (Cys-C), uric acid (URIC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), non-HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C, TG/HDL-C, TC/HDL-C, TyG, and TyG-BMI were risk factors for MAFLD. The odds ratio of TG/HDL-C and TyG were 5.629 (95%CI: 3.039-10.424) and 182.474 (95%CI: 33.518-993.407), respectively. In identifying MAFLD, TyG, TyG-BMI, TG, and TG/HDL-C were found to be the most vital indexes based on the random forest method, with the area under the curve (AUC) greater than 0.9. In addition, the combination of BMI, ALT, and TyG had a high diagnostic efficiency for MAFLD. CONCLUSIONS:TyG and TG/HDL-C were potential risk factors for MAFLD, and the former performed better in diagnosing MAFLD. The combination of BMI, ALT, and TyG improved the diagnostic capability for MAFLD.
10.1186/s12944-022-01661-7
Impact of rumination on sleep quality among patients with non‑alcoholic fatty liver disease: a moderated mediation model of anxiety symptoms and resilience.
BMC psychiatry
BACKGROUND:Poor sleep raises the risk of non-alcoholic fatty liver disease (NAFLD) and hastens disease progression. It is critical to figure out what factors impact the sleep quality of NAFLD patients. The present study aimed to investigate the role of anxiety symptoms in accounting for the impact of rumination on sleep quality and the moderating role of resilience on the associations of rumination with anxiety symptoms and sleep quality. METHODS:In the cross-sectional study, 285 NAFLD patients completed the Chinese version of the Pittsburgh Sleep Quality Index, the Ruminative Responses Scale, the Generalized Anxiety Disorder 7-item scale, and the 14-item Resilience Scale to measure sleep quality, rumination (including brooding and reflection), anxiety symptoms, and resilience, respectively. The PROCESS macro for SPSS v4.0 procedure was applied to perform moderated mediation analysis. RESULTS:The roles of anxiety symptoms in accounting for the positive associations of brooding, reflection and rumination with poor sleep quality were revealed. It was found that there was a significant moderating role of resilience on the positive associations of brooding, reflection and rumination with anxiety symptoms, which were gradually reduced as resilience increased. The direct associations between brooding, reflection and rumination and poor sleep quality were not significantly moderated by resilience. Thus, a moderated mediation model involving anxiety symptoms and resilience for explaining the impact of rumination on poor sleep quality was supported among patients with NAFLD. CONCLUSIONS:Rumination (including brooding and reflection) could be positively related to poor sleep quality, and anxiety symptoms had a significant role in accounting for the relationship among patients with NAFLD. Resilience showed a moderating role that could attenuate the positive association between rumination and anxiety symptoms. Interventions aimed at alleviating rumination, reducing anxiety symptoms, and enhancing resilience could improve the sleep quality of NAFLD patients.
10.1186/s12888-023-04572-8
Association of iron status with non-alcoholic fatty liver disease and liver fibrosis in US adults: a cross-sectional study from NHANES 2017-2018.
Food & function
: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder resulting in a high risk of adverse prognosis, and its presence has been considered a cause or an outcome of metabolic syndrome. But the relative factors and mechanism of NAFLD are still unclear. The aim of this study is to explore the association between iron status indicators and NAFLD as well as liver fibrosis. : This study evaluated whether serum iron status indicators are independently related to the risk of NAFLD. The independent variable was each one of the iron status indicators (iron intake, ferritin, iron, unsaturated iron binding force (UIBC), total iron binding capacity (TIBC), transferrin saturation, transferrin receptor, hemoglobin, and mean cell hemoglobin), and the dependent variables were NAFLD and advanced liver fibrosis. A multivariable logistic regression analysis and subgroup analysis were performed to evaluate the association between iron status indicators and NAFLD as well as liver fibrosis. : A total of 3727 patients were included. After adjusting for other covariates in multiple logistic regression models, the serum ferritin, UIBC, TIBC, and hemoglobin had a significant positive association with the NAFLD (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.09, 1.23; 1.31, 95% CI: 1.06, 1.62; 1.82, 95% CI: 1.23, 2.67; 2.67, 95% CI: 1.48, 4.82, separately), and the risk of NAFLD diagnosed by VCTE or ALT/AST further increased in the fourth quartile group of serum ferritin (diagnosed by VCTE OR = 1.93, 95% CI: 1.49, 2.50; diagnosed by ALT/AST OR = 5.76, 95% CI: 3.96, 8.38). Moreover, the main positive correlation between serum ferritin and NAFLD was found in females, participants aged >41 years, with no diabetes. : Our results indicated that iron status indicators were closely associated with the occurrence of advanced liver fibrosis, which may indicate that iron status indicators could be potential biomarkers of NAFLD and advanced liver fibrosis.
10.1039/d2fo04082d
Effects of Thyroid Hormones on Lipid Metabolism Pathologies in Non-Alcoholic Fatty Liver Disease.
Biomedicines
The typical modern lifestyle contributes to the development of many metabolic-related disorders, as exemplified by metabolic syndrome. How to prevent, resolve, or avoid subsequent deterioration of metabolic disturbances and the development of more serious diseases has become an important and much-discussed health issue. Thus, the question of the physiological and pathological roles of thyroid hormones (THs) in metabolism has never gone out of fashion. Although THs influence almost all organs, the liver is one of the most important targets as well as the hub of metabolic homeostasis. When this homeostasis is out of balance, diseases may result. In the current review, we summarize the common features and actions of THs, first focusing on their effects on lipid metabolism in the liver. In the second half of the review, we turn to a consideration of non-alcoholic fatty liver disease (NAFLD), a disease characterized by excessive accumulation of fat in the liver that is independent of heavy alcohol consumption. NAFLD is a growing health problem that currently affects ~25% of the world's population. Unfortunately, there are currently no approved therapies specific for NAFLD, which, if left uncontrolled, may progress to more serious diseases, such as cirrhosis or liver cancer. This absence of effective treatment can also result in the development of non-alcoholic steatohepatitis (NASH), an aggressive form of NAFLD that is the leading cause of liver transplantation in the United States. Because THs play a clear role in hepatic fat metabolism, their potential application in the prevention and treatment of NAFLD has attracted considerable research attention. Studies that have investigated the use of TH-related compounds in the management of NAFLD are also summarized in the latter part of this review. An important take-home point of this review is that a comprehensive understanding of the physiological and pathological roles of THs in liver fat metabolism is possible, despite the complexities of this regulatory axis-an understanding that has clinical value for the specific management of NAFLD.
10.3390/biomedicines10061232
Development of Thyroid Hormones and Synthetic Thyromimetics in Non-Alcoholic Fatty Liver Disease.
International journal of molecular sciences
Non-alcoholic fatty liver disease (NAFLD) is the fastest-growing liver disease in the world. Despite targeted agents which are needed to provide permanent benefits for patients with NAFLD, no drugs have been approved to treat NASH. Thyroid hormone is an important signaling molecule to maintain normal metabolism, and in vivo and vitro studies have shown that regulation of the 3,5,3'-triiodothyronine (T3)/ thyroid hormone receptor (TR) axis is beneficial not only for metabolic symptoms but also for the improvement of NAFLD and even for the repair of liver injury. However, the non-selective regulation of T3 to TR subtypes (TRα/TRβ) could cause unacceptable side effects represented by cardiotoxicity. To avoid deleterious effects, TRβ-selective thyromimetics were developed for NASH studies in recent decades. Herein, we will review the development of thyroid hormones and synthetic thyromimetics based on TR selectivity for NAFLD, and analyze the role of TR-targeted drugs for the treatment of NAFLD in the future.
10.3390/ijms23031102
Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists.
Thyroid : official journal of the American Thyroid Association
Thyroid hormones (THs) exert a strong influence on mammalian lipid metabolism at the systemic and hepatic levels by virtue of their roles in regulating circulating lipoprotein, triglyceride (TAG), and cholesterol levels, as well as hepatic TAG storage and metabolism. These effects are mediated by intricate sensing and feedback systems that function at the physiological, metabolic, molecular, and transcriptional levels in the liver. Dysfunction in the pathways involved in lipid metabolism disrupts hepatic lipid homeostasis and contributes to the pathogenesis of metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD) and hypercholesterolemia. There has been strong interest in understanding and employing THs, TH metabolites, and TH mimetics as lipid-modifying drugs. THs regulate many processes involved in hepatic TAG and cholesterol metabolism to decrease serum cholesterol and intrahepatic lipid content. TH receptor β analogs designed to have less side effects than the natural hormone are currently being tested in phase II clinical studies for NAFLD and hypercholesterolemia. The TH metabolites, 3,5-diiodo-l-thyronine (T2) and T1AM (3-iodothyronamine), have different beneficial effects on lipid metabolism compared with triiodothyronine (T3), although their clinical application is still under investigation. Also, prodrugs and glucagon/T3 conjugates have been developed that direct TH to the liver. TH-based therapies show clinical promise for the treatment of NAFLD and hypercholesterolemia. Strategies for limiting side effects of TH are being developed and may enable TH metabolites and analogs to have specific effects in the liver for treatments of these conditions. These liver-specific effects and potential suppression of the hypothalamic/pituitary/thyroid axis raise the issue of monitoring liver-specific markers of TH action to assess clinical efficacy and dosing of these compounds.
10.1089/thy.2018.0664
Impaired Sensitivity to Thyroid Hormones Is Associated with Hyperuricemia, Obesity, and Cardiovascular Disease Risk in Subjects with Subclinical Hypothyroidism.
Thyroid : official journal of the American Thyroid Association
Subclinical hypothyroidism (SCH) is associated with an increased risk of metabolic disorders and cardiovascular events. There is a delicate interplay between thyroid hormones and thyrotropin (TSH) and metabolic homeostasis. However, the association between thyroid hormone sensitivity and metabolic indices has not been elucidated in SCH. We enrolled 11,109 participants with SCH. All participants had a TSH level >4.2 mIU/L and normal free thyroxine (fT4; 12.0-22.0 pmol/L). Metabolic indices (body mass index [BMI], blood pressure, serum lipid, serum uric acid [sUA], plasma glucose and glycosylated hemoglobin [HbA1]) were measured. The thyroid hormone sensitivity indices that include thyroid feedback quantile-based index (TFQI), TSH index (TSHI), and thyrotroph thyroxine resistance index (TT4RI) were calculated based on fT4 and TSH. Higher TFQI quartiles indicated lower thyroid hormone sensitivity. The relationship between thyroid hormone sensitivity indices and metabolic indices and cardiovascular disease (CVD) risk were calculated. Participants with decreased central sensitivity to thyroid hormone had lower BMI and higher sUA levels. The odds ratio of the fourth versus the first quartile of TFQI was 0.85 [confidence interval, CI: 0.73-0.96] for obesity, 1.64 [CI: 1.37-1.92] for hyperuricemia (HUA), and 12.22 [CI: 5.32-28.07] for 10-year risk distribution for CVD >20%. Further adjustment for BMI when analyzing HbA1, HUA, and CVD risk generated similar results. TSHI and TT4RI also yielded similar results. Impaired sensitivity to thyroid hormone in SCH is associated with higher risk of HUA and CVD and lower risk of obesity. These findings are potentially useful for understanding the interaction between thyroid hormone sensitivity and metabolic diseases in SCH.
10.1089/thy.2021.0500
Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study.
van den Berg Eline H,van Tienhoven-Wind Lynnda J N,Amini Marzyeh,Schreuder Tim C M A,Faber Klaas Nico,Blokzijl Hans,Dullaart Robin P F
Metabolism: clinical and experimental
OBJECTIVE:Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects. METHODS:The study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5-4.0mU/L, free thyroxine (FT4) 11-19.5pmol/L and free triiodothyronine (FT3) 4.4-6.7pmol/L) older than 18years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI≥60 was categorized as NAFLD. A P<0.01 was considered significant. RESULTS:FLI≥60 was found in 4274 (21.1%) of 20,289 individuals (62.1% male, median age 46years) with increased prevalence of MetS (P<0.0001). In age- and sex-adjusted analysis FLI≥60 was independently associated with a higher FT3 (OR 1.34, 95% CI 1.29-1.39, per SD increment, P<0.0001) and a lower FT4 (OR 0.73, 95% CI 0.70-0.75, P<0.0001) but not by TSH. The strongest association was found for the FT3/FT4 ratio (OR 1.44, 95% CI 1.39-1.49, P<0.0001). These associations remained similar after additional adjustment for the presence of MetS. In subjects with enlarged waist circumference, TSH and FT4 were lower while FT3 was higher, resulting in an increased FT3/FT4 ratio (P<0.0001). CONCLUSIONS:Euthyroid subjects with suspected NAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity.
10.1016/j.metabol.2016.11.002
Association of long-term ambient fine particulate matter (PM) and incident non-alcoholic fatty liver disease in Chinese adults.
Environmental pollution (Barking, Essex : 1987)
Air pollution is increasingly recognized as an important environmental risk factor for non-alcoholic fatty liver disease (NAFLD). However, epidemiologic evidence on long-term exposure to high air pollution concentrations with incident NAFLD is still very limited. Here, we constructed a population-based dynamic cohort involving 17,106 subjects who were enrolled between 2005 and 2013 and subsequently followed until 2017, combined with a high-resolution ambient fine particulate matter ≤2.5 μm (PM) dataset, to investigate the association of long-term PM exposure (cumulative annual average levels ranged from 36.67 to 111.16 μg/m) with NAFLD incidence (N = 4,640). We estimated the adjusted hazard ratio (HR) for incident NAFLD among those exposed to the highest quartile of PM was 2.04 [95% confidence interval (CI), 1.80-2.30] compared with individuals exposed to the lowest quartile of PM. The dose-response relationships for PM are non-linear for NAFLD across the exposure distribution. Further stratified analyses revealed that lean (<23 kg/m), younger (<40-year-old), and women individuals appeared more vulnerable to the harmful effects of PM exposure. Our study suggests a greater long-term high ambient PM exposure is associated with an increased risk of NAFLD in Chinese adults, particularly in specific groups, including lean, women, and younger people.
10.1016/j.envpol.2023.121666
PM air pollution exposure and nonalcoholic fatty liver disease in the Nationwide Inpatient Sample.
Environmental research
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Particulate matter air pollution <2.5 μm in diameter (PM) is a ubiquitous exposure primarily produced from fossil fuel combustion. Previous epidemiologic studies have been mixed. The objective of this study was to examine the association between ambient PM exposure and NAFLD among hospitalized patients in the Nationwide Inpatient Sample (NIS). METHODS:We conducted a cross-sectional analysis of hospitalizations from 2001 to 2011 using the NIS, the largest nationally representative all-payer inpatient care administrative database in the United States. Average annual PM exposure was estimated by linking census tracts (based on NIS-provided hospital ZIP Codes) with a spatiotemporal exposure model. Clinical conditions were identified using hospital discharge diagnosis codes. Multivariable logistic regression incorporating discharge weights was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PM exposure and odds of NAFLD among hospitalized patients adjusting for age, sex, race/ethnicity, year, individual- and area-level socioeconomic status, urbanicity, region, obesity, diabetes, metabolic syndrome, impaired fasting glucose, dyslipidemia, hypertension, obstructive sleep apnea, and smoking. RESULTS:There were 269,705 hospitalized patients with NAFLD from 2001 to 2011 (total unweighted n = 45,433,392 hospitalizations). Higher ambient PM exposure was associated with increased odds of NAFLD among hospitalized patients (adjusted OR: 1.24 per 10 μg/m increase, 95% CI 1.15-1.33, p < 0.01). There were statistically significant interactions between PM exposure and age, race/ethnicity, diabetes, smoking, and region, with stronger positive associations among patients who were aged ≥45 years, non-Hispanic White or Asian/Pacific Islander, non-diabetics, non-smokers, or in the Midwest and West regions, respectively. CONCLUSIONS:In this nationwide cross-sectional analysis of the NIS database, there was a positive association between ambient PM exposure and odds of NAFLD among hospitalized patients. Future research should examine the effects of long-term historical PM exposure and incident NAFLD cases.
10.1016/j.envres.2022.113611
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
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
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
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
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
Olanzapine-induced liver injury in mice: aggravation by high-fat diet and protection with sulforaphane.
Isaacson Robin H,Beier Juliane I,Khoo Nicholas Kh,Freeman Bruce A,Freyberg Zachary,Arteel Gavin E
The Journal of nutritional biochemistry
Olanzapine is effective to treat for schizophrenia and other mood disorders, but limited by side effects such as weight gain, dyslipidemia, and liver injury. Obesity in the US is at epidemic levels, and is a significant risk factor for drug-induced liver injury. Obesity incidence in the psychiatric population is even higher than in the US population as a whole. The purpose of this study was to test the hypothesis that obesity worsens olanzapine-induced hepatic injury, and to investigate the potential protective effects of sulforaphane. 8-week old female C57BL/6 mice were fed either a high-fat or low-fat control diet (HFD and LFD). Mice also received either olanzapine (8 mg/kg/d) or vehicle by osmotic minipump for 4 weeks. A subset of mice in the HFD + olanzapine group was administered sulforaphane, a prototypical Nrf2 inducer (90 mg/kg/d). Olanzapine alone increased body weight, without a commensurate increase in food consumption. Olanzapine also caused hepatic steatosis and injury. Combining olanzapine and HFD caused further dysregulation of glucose and lipid metabolism. Liver damage from concurrent HFD and olanzapine was worse than liver damage from high-fat diet or olanzapine alone. Sulforaphane alleviated many metabolic side effects of olanzapine and HFD. Taken together, these data show that olanzapine dysregulates glucose and lipid metabolism and exacerbates hepatic changes caused by eating a HFD. Activation of the intrinsic antioxidant defense pathway with sulforaphane can partially prevent these effects of olanzapine and may represent a useful strategy to protect against liver injury.
10.1016/j.jnutbio.2020.108399
Olanzapine-induced nonalcoholic fatty liver disease: The effects of differential food pattern and the involvement of PGRMC1 signaling.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Detrimental dietary habits with high-fat food are common in the psychiatric population, leading to higher obesity rate. Olanzapine (OLZ), as one of the mainstream antipsychotic drugs, shows superior efficacy in treating schizophrenia but limited by adverse effects such as obesity, dyslipidemia and liver injury, which are risk factors for the development of nonalcoholic fatty liver disease (NAFLD). Progesterone receptor component 1 (PGRMC1) is a key regulator associated with antipsychotic drug-induced metabolic disorders. Our study aims to investigate whether high-fat supplementation worsens OLZ-induced NAFLD and to validate the potential role of PGRMC1 pathway. In vivo, eight-week OLZ treatment successfully induced hepatic steatosis in female C57BL/6 mice fed with either a high-fat or normal diet, which is independent of body weight gain. Likewise, in vitro, OLZ markedly led to hepatocyte steatosis along with enhanced oxidative stress, which was aggravated by free fatty acids. Moreover, in vivo and in vitro, high-fat supplementation aggravated OLZ-induced hepatic lipid accumulation and oxidative stress via inhibition of hepatic PGRMC1-AMPK-mTORC1/Nrf2 pathways. Inspiringly, PGRMC1 overexpression effectively reversed OLZ-induced hepatocyte steatosis in vitro. Hence, hepatic PGRMC1 is attributable to OLZ-induced NAFLD especially with high-fat supplementation and potentially serves as a novel therapeutic target.
10.1016/j.fct.2023.113757
Nonalcoholic fatty liver disease.
Brunt Elizabeth M,Wong Vincent W-S,Nobili Valerio,Day Christopher P,Sookoian Silvia,Maher Jacquelyn J,Bugianesi Elisabetta,Sirlin Claude B,Neuschwander-Tetri Brent A,Rinella Mary E
Nature reviews. Disease primers
Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring.
10.1038/nrdp.2015.80
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
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
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
Prevalence and Risk Factors of Metabolic Associated Fatty Liver Disease in Xinxiang, China.
Li Hongbin,Guo Meihao,An Zhen,Meng Jun,Jiang Jing,Song Jie,Wu Weidong
International journal of environmental research and public health
Metabolic associated fatty liver disease (MAFLD) is recognized as the liver disease component of metabolic syndrome, which is mainly related to insulin resistance and genetic susceptibility. It is the most prevalent chronic liver disease worldwide. With rapid lifestyle transitions, its prevalence worldwide is increasing, and tremendous challenges in controlling this pandemic are arising. The objective of this study was to investigate the prevalence and risk factors of MAFLD in rural areas of Xinxiang, Henan in 2017. We conducted a cross-sectional analysis of rural inhabitants aged 20-79 years in Xinxiang, Henan in 2017, using cluster random sampling ( = 9140). Physical examinations were conducted at local clinics from April to June 2017. After overnight fasting, all participants underwent physical examinations, blood routine tests, biochemical examinations, and liver ultrasound and completed questionnaires. We investigated the crude and age-adjusted MAFLD prevalence and analyzed the characteristics of those with, and without, MAFLD, using logistic regression. Approximately 2868 (31.38%) participants were diagnosed with MAFLD. The overall age-adjusted MAFLD prevalence was 29.85% (men: 35.36%; women: 26.49%). The MAFLD prevalence increased with age, and peaked at the 50-59-year age group, and then began to decline. Higher body mass index, waist circumference, percentage of lymphocytes, levels of hemoglobin, platelet count, triglyceride, fasting plasma glucose, and serum uric acid were independently and positively correlated with MAFLD; In contrary, active physical activity and high-density lipoprotein cholesterol were negatively correlated with MAFLD. In summary, the MAFLD prevalence in the study population was 29.85%. Higher body mass index, waist circumference, percentage of lymphocytes, levels of hemoglobin, platelet count, triglyceride, fasting plasma glucose, and serum uric acid were risk factors for MAFLD.
10.3390/ijerph17061818
The prevalence of alcoholic and nonalcoholic fatty liver disease in adolescents and young adults in the United States: analysis of the NHANES database.
BMC gastroenterology
BACKGROUND:The prevalence of fatty liver disease is potentially increasing in adolescents and young adults (AYAs) due to the obesity and alcohol pandemics. The aim of this study was to assess the prevalence of alcohol-associated fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) in a representative U.S. cohort utilizing transient elastography to directly measure hepatic steatosis and suspected fibrosis. METHODS:AYAs (age 15-39 years) with valid FibroScan measurements in the National Health and Nutrition Examination Survey (NHANES) database (2017-2018) were included in the analyses. Those with viral hepatitis, pregnancy, or ALT/AST > 500 U/L were excluded. The population was divided into those with excessive alcohol consumption (ALQ130) and those without. Controlled attenuation parameter (CAP) score ≥ 248 dB/m was used to identify suspected ALD and NAFLD. In those with evidence of ALD, the following cutoffs of liver stiffness measurement (LSM) were used for suspected fibrosis: F ≥ F2 at LSM ≥ 7.5 kPa and F ≥ F3 at ≥ 9.5 kPa, respectively. In those with suspected NAFLD, the following LSM cutoffs were used: F ≥ F2 at 6.1 and F ≥ F3 at ≥ 7.1, respectively. Cutoffs were chosen based on published literature to maximize sensitivity. RESULTS:Comparing to those without, subjects with excessive alcohol consumption tended to be older (29.8 vs 28.5 years), have a higher BMI (29.3 vs 28.9 kg/m2), and be from a White ethnicity (65.3% vs. 55.4%). In subjects with excessive alcohol consumption, suspected ALD was present in 56.59% (95% CI 41.57-70.49). In those with suspected ALD, suspected significant fibrosis (F ≥ F2) was present in 12.3% (95% CI 4.74-28.34) and advanced fibrosis (F ≥ F3) was present in 6.31% (95% CI 0.69-39.55). Similarly, in subjects without excessive alcohol consumption, suspected NAFLD was present in 40.04% (36.64-43.54). In those with suspected NAFLD, suspected significant fibrosis (F ≥ F2) was present in 31.07% (27.25-35.16) and suspected advanced fibrosis (F ≥ F3) was present in 20.15% (16.05-24.99). CONCLUSION:A significant percentage of AYAs are at risk for ALD and NAFLD and a subset of these subjects is at risk for significant fibrosis. Efforts should focus on increasing awareness of the prevalence of ALD and NAFLD in this population and to mitigate modifiable risk factors.
10.1186/s12876-022-02430-7
Association between nonalcoholic fatty liver disease and depression: A systematic review and meta-analysis of observational studies.
Journal of affective disorders
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is associated with an increased prevalence of psychological conditions such as depression and anxiety. However, the correlation between NAFLD and depression has not been well illustrated. METHODS:Studies that investigate the association between nonalcoholic fatty liver disease and depression were searched in multiple electronic databases. Pooled odds ratios (ORs) and confidence intervals (CIs) of the included articles were calculated using a fixed- or random effects model. RESULTS:A total of seven articles were included in this study. The results of the meta-analysis showed that compared with those without nonalcoholic fatty liver disease, individuals with it had a significantly increased risk of depression (pooled OR = 1.13, 95% CI: 1.03, 1.24, p = 0.007), and there was evidence that heterogeneity was not significant (I = 13.6%, p for heterogeneity = 0.324). Moreover, depressed patients had a significantly increased risk of developing nonalcoholic fatty liver disease compared with non-depressed patients (pooled OR = 1.46, 95% CI: 1.15, 1.85, p = 0.002), and evidence of non-significant heterogeneity was observed (I = 0%, p = 0.837 for heterogeneity). LIMITATIONS:The majority of the included articles in this study are cross-sectional studies and could not elucidate the causal relationship, so further longitudinal studies are needed to clarify the causal relationship. CONCLUSION:Nonalcoholic fatty liver and depression are highly correlated, the two interact with each other and have a high risk of comorbidities. In the future more high quality prospective studies will be needed to validate our results.
10.1016/j.jad.2021.12.128
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
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
Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRα/PCSK9 pathway.
Scientific reports
Studies have confirmed that olanzapine, the mainstay treatment for schizophrenia, triggers metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). However, the etiology of olanzapine-induced NAFLD is poorly understood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9. The purpose of this study was to investigate the role of PCSK9 and explore the therapeutic effect of metformin for olanzapine-associated NAFLD. Olanzapine significantly upregulated PCSK9 and promoted lipid accumulation in mouse livers and HepG2 and AML12 cells. Metformin ameliorated these pathological alterations. PCSK9 upstream regulator liver X receptor α (LXRα) was significantly upregulated in olanzapine-induced NAFLD. LXRα antagonist treatment and LXRα overexpression resulted in a decrease and increase of PCSK9, respectively. Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid β-oxidation (SCAD and PPARα) were downregulated, while metformin reversed these changes. In addition, we found that LXRα overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation. Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRα, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARα, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.
10.1038/s41598-022-09610-1
Prevalence of nonalcoholic fatty liver disease in mental disorder inpatients in China: an observational study.
Ma Qiuyue,Yang Fude,Ma Botao,Jing Wenzhan,Liu Jue,Guo Moning,Li Juan,Wang Zhiren,Liu Min
Hepatology international
BACKGROUND AND PURPOSE:Non-alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease in China. However, the understanding of NAFLD prevalence among Chinese mental disorder inpatients remains insufficient. We aim to investigate the prevalence of NAFLD among mental disorder inpatients in Beijing, China. METHODS:In this observational study, we included 66,273 mental disorder inpatients between 2014 and 2018, including inpatients with schizophrenia, bipolar disorder, depressive disorder and other mental disorders. Data were obtained from electronic health records of 19 specialized psychiatric hospitals in Beijing. NAFLD was defined by ICD-10 code, excluding other causes of liver disease. We calculated the overall and annual prevalence rates of NAFLD from 2014 to 2018, and compared NAFLD prevalence between sexes, age groups, mental disorders types, antipsychotics use, and comorbidities. Multivariable logistic regression was used to examine risk factors associated with NAFLD. Subgroup analysis was performed in different mental disorder types. RESULTS:The prevalence of NAFLD was 17.63% (95% CI 17.34-17.92%) in mental disorder inpatients, increasing from 16.88% in 2014 to 19.07% in 2018. The NAFLD prevalence in participants with schizophrenia (22.44%) was higher than that in participants with bipolar disorder (17.89%), depressive disorder (12.62%), and other mental disorders (12.99%). Women had similar or even higher NAFLD prevalence than men after 50 years. Men, 50-59 years (aOR = 1.71), schizophrenia (aOR = 1.56), bipolar disorder (aOR = 1.47), antipsychotics use (aOR = 1.46), hypertension (aOR = 1.50), diabetes (aOR = 1.83), dyslipidemia (aOR = 2.50) were risk factors for NAFLD in mental disorder inpatients. CONCLUSION:NAFLD was common among Chinese mental disorder inpatients, and increased over years. The prevalence of NAFLD was higher among men, old women, inpatients with schizophrenia, bipolar disorder, antipsychotics, hypertension, diabetes, and dyslipidemia. Fatty liver disease among mental disorder population warrants the attention of psychiatric specialists and health policy-makers.
10.1007/s12072-020-10132-z
The prevalence and risk factors of young male schizophrenics with non-alcoholic fatty liver disease.
Yan Jing,Hou Chengye,Liang Ying
Neuropsychiatric disease and treatment
OBJECTIVE:In this study, we compared the prevalence rate of non-alcoholic fatty liver disease (NAFLD) between young males with schizophrenia and the general young males as the control group, and we also investigated the risk factors of NAFLD in young males with schizophrenia. MATERIALS AND METHODS:This is a large cross-sectional study consisting of the study group and parallel control group. The study group comprises 202 cases of young males with schizophrenia recruited from Liaoning province Demobilized Soldiers Kangning Hospital, and 149 healthy young males were recruited as the control group. The clinical evaluation included Positive and Negative Syndrome Scale (PANSS), basic information, disease-related information, and physical examination information. The laboratory tests included fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The physical examination included liver ultrasonography. RESULTS:No statistical difference was observed between the study and control groups regarding age (30.5±3.9 vs 30.7±3.6), body mass index (BMI), blood pressure, fasting glucose level, and total cholesterol. NAFLD was observed in both the study and control groups. The prevalence of NAFLD was 49.5% (100/202) in the study group, and 20.1% (30/149) in the control group. The study group was further divided into NAFLD group and non-NAFLD group. There were significant differences in medication combination, drug dosage, negative factor score in PANSS (14.1±4.0 vs 12.7±4.5), BMI, fasting glucose level, total cholesterol, triglyceride, ALT, and AST between NAFLD group and non-NAFLD group. According to the results of the multiple-factor analysis, the onset of NAFLD among young males with schizophrenia was significantly correlated with the following factors: triglyceride, BMI, medication combination, drug dosage, and negative factor score in PANSS. CONCLUSION:The prevalence of NAFLD in the study group was significantly higher than that in the control group. Multivariate analysis indicated that, triglyceride, BMI, medication combination, drug dosage, and negative factor score in PANSS were significantly related to NAFLD in patients with schizophrenia.
10.2147/NDT.S137183
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
Understanding Mechanisms Underlying Non-Alcoholic Fatty Liver Disease (NAFLD) in Mental Illness: Risperidone and Olanzapine Alter the Hepatic Proteomic Signature in Mice.
Rostama Bahman,Beauchemin Megan,Bouchard Celeste,Bernier Elizabeth,Vary Calvin P H,May Meghan,Houseknecht Karen L
International journal of molecular sciences
Patients with severe mental illness have increased mortality, often linked to cardio-metabolic disease. Non-alcoholic fatty liver disease (NAFLD) incidence is higher in patients with schizophrenia and is exacerbated with antipsychotic treatment. NAFLD is associated with obesity and insulin resistance, both of which are induced by several antipsychotic medications. NAFLD is considered an independent risk factor for cardiovascular disease, the leading cause of death for patients with severe mental illness. Although the clinical literature clearly defines increased risk of NAFLD with antipsychotic therapy, the underlying mechanisms are not understood. Given the complexity of the disorder as well as the complex pharmacology associated with atypical antipsychotic (AA) medications, we chose to use a proteomic approach in healthy mice treated with a low dose of risperidone (RIS) or olanzapine (OLAN) for 28 days to determine effects on development of NAFLD and to identify pathways impacted by AA medications, while removing confounding intrinsic effects of mental illness. Both AA drugs caused development of steatosis in comparison with vehicle controls ( < 0.01) and affected multiple pathways relating to energy metabolism, NAFLD, and immune function. AA-associated alteration in autonomic function appears to be a unifying theme in the regulation of hepatic pathology.
10.3390/ijms21249362
Liver Function Test Abnormalities in Depressed Patients Treated with Antidepressants: A Real-World Systematic Observational Study in Psychiatric Settings.
Voican Cosmin Sebastian,Martin Severine,Verstuyft Céline,Corruble Emmanuelle,Perlemuter Gabriel,Colle Romain
PloS one
BACKGROUND:Concerning the risk of antidepressant induced liver injury, it is not clear whether psychiatrists perform a liver function test (LFT) and whether an increase in aminotransferase levels should contraindicate antidepressant treatment. AIM:To evaluate LFT availability, the prevalence of LFT abnormalities and the probable cause of an altered LFT in patients with a major depressive episode (MDE) requiring an antidepressant drug. METHODS:We studied LFT evaluation in a real world psychiatric setting, in a sample of 321 consecutive patients with a current major depressive episode (MDE) requiring an antidepressant drug treatment, but without current alcohol or drug dependence or unstable medical disease. RESULTS:An LFT is performed in 36.1% (116/321) of depressed patients. One fifth of antidepressant-treated patients who had an LFT evaluation had abnormal results. The most frequent causes of LFT abnormalities were: NAFLD (nonalcoholic fatty liver disease) (7/321; 2.1%), acute alcohol consumption (4/321; 1.2%), antidepressant-induced liver injury (3/321; 0.9%), hepatitis C virus infection (2/321; 0.6%) and heart failure (1/321; 0.3%). The cause of LFT abnormalities was unknown in 32% of patients (8/25) due to the absence of etiological investigations. CONCLUSION:These results demonstrate that an LFT is infrequently performed by psychiatrists in depressed patients requiring an antidepressant drug. Baseline LFT assessment and observations during the first six months of antidepressant treatment may be useful for detection of patients with pre-existing liver disease such as NAFLD, and early identification of cases of antidepressant-induced liver injury. An increase in aminotransferase levels may be related to an underlying liver disease, but does not contraindicate antidepressant treatment.
10.1371/journal.pone.0155234
Risperidone Exacerbates Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Renal Impairment in Obese Mice.
Tsai Hsiao-Pei,Hou Po-Hsun,Mao Frank-Chiahung,Chang Chia-Chia,Yang Wei-Cheng,Wu Ching-Feng,Liao Huei-Jyuan,Lin Tzu-Chun,Chou Lan-Szu,Hsiao Li-Wei,Chang Geng-Ruei
International journal of molecular sciences
Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury.
10.3390/ijms22010409
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
Elevated prevalence of obesity, metabolic syndrome, and cardiovascular risk factors in bipolar disorder.
Fiedorowicz Jess G,Palagummi Narasimha M,Forman-Hoffman Valerie L,Miller Del D,Haynes William G
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists
BACKGROUND:Bipolar disorder is associated with excess cardiovascular mortality. We hypothesized outpatients with bipolar disorder would exhibit excess cardiovascular risk factors, particularly among prevalent users of the second-generation antipsychotics associated with weight gain and valproic acid derivatives. METHODS:This chart review of 217 patients with bipolar disorder examined cardiovascular risk factors of the metabolic syndrome. We also evaluated if certain medications were cross-sectionally associated with metabolic syndrome. RESULTS:Fifty-six patients were not weighed and many did not have available lipid profiles. Over three-quarters of those with available data (n = 161) were overweight or obese (body mass index >or= 25) and nearly half were obese (body mass index >or= 30). A prevalence exceeding general population estimates was also observed for hypertriglyceridemia, elevated blood pressure/hypertension, and elevated fasting glucose/diabetes. Among those with all requisite data (n = 60), over 50% met criteria for National Cholesterol Education Program-defined metabolic syndrome, nearly double the expected prevalence. A trend toward greater prevalence of metabolic syndrome among prevalent users of the second-generation antipsychotics associated with weight gain was observed. CONCLUSIONS:Obesity and the metabolic syndrome were common in patients with bipolar disorder. These patients may be under-evaluated for cardiovascular risk and warrant screening and early intervention.
10.1080/10401230802177722
Sex Difference in the Association between Serum Homocysteine Level and Non-Alcoholic Fatty Liver Disease.
Won Bo-Youn,Park Kyung-Chae,Lee Soo-Hyun,Yun Sung-Hwan,Kim Moon-Jong,Park Kye-Seon,Kim Young-Sang,Haam Ji-Hee,Kim Hyung-Yuk,Kim Hye-Jung,Park Ki-Hyun
Korean journal of family medicine
BACKGROUND:The relationship between serum homocysteine levels and non-alcoholic fatty liver disease is poorly understood. This study aims to investigate the sex-specific relationship between serum homocysteine level and non-alcoholic fatty liver disease in the Korean population. METHODS:This cross-sectional study included 150 men and 132 women who participated in medical examination programs in Korea from January 2014 to December 2014. Patients were screened for fatty liver by abdominal ultrasound and patient blood samples were collected to measure homocysteine levels. Patients that consumed more than 20 grams of alcohol per day were excluded from this study. RESULTS:The homocysteine level (11.56 vs. 8.05 nmol/L) and the proportion of non-alcoholic fatty liver disease (60.7% vs. 19.7%) were significantly higher in men than in women. In men, elevated serum homocysteine levels were associated with a greater prevalence of non-alcoholic fatty liver disease (quartile 1, 43.6%; quartile 4, 80.6%; P=0.01); however, in females, there was no significant association between serum homocysteine levels and the prevalence of non-alcoholic fatty liver disease. In the logistic regression model adjusted for age and potential confounding parameters, the odds ratio for men was significantly higher in the uppermost quartile (model 3, quartile 4: odds ratio, 6.78; 95% confidential interval, 1.67 to 27.56); however, serum homocysteine levels in women were not associated with non-alcoholic fatty liver disease in the crude model or in models adjusted for confounders. CONCLUSION:Serum homocysteine levels were associated with the prevalence of non-alcoholic fatty liver disease in men.
10.4082/kjfm.2016.37.4.242
Serum homocysteine levels in patients with nonalcoholic fatty liver disease.
Polyzos Stergios A,Kountouras Jannis,Patsiaoura Kalliopi,Katsiki Evangelia,Zafeiriadou Efthimia,Deretzi Georgia,Zavos Christos,Gavalas Emmanouel,Katsinelos Panagiotis,Mane Vasileia,Slavakis Aristidis
Annals of hepatology
Background and rational for the study. Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic component of insulin resistance (IR) syndrome, but data on serum homocysteine (HCY) are limited. The aim of the study was the evaluation of serum HCY levels in patients with NAFLD. Material and methods. Thirty-one patients (54 ± 11 years, 8 males) with biopsy-proven NAFLD, 15 with simple nonalcoholic fatty liver (NAFL) and 16 with nonalcoholic steatohepatitis (NASH), and 22 healthy controls (52 ± 9 years, 5 males) matched for gender, age and body mass index (BMI), were recruited. Blood samples for HCY, folate, vitamin B12, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance (HOMA-IR) was calculated. Results. There was no difference in mean serum HCY levels between controls and NAFLD patients (12.6 ± 4.6 vs. 13.5 ± 2.6 mmol/L, respectively; p = 0.432). Serum folate and vitamin B12 were also similar between the study groups. Mean age, BMI, serum folate and vitamin B12 did not differ between NAFL and NASH patients. However, when compared with NAFL patients, NASH patients had lower mean serum HCY levels (12.3 ± 2.5 vs. 14.7 ± 2.1 mmol/L; p = 0.006). HCY was lower by increasing the grading of fibrosis (p = 0.005), portal inflammation (p = 0.029) and steatosis location (p = 0.021). In logistic regression analysis, HCY independently predicted NASH (p = 0.045) after adjustment for gender, age, BMI, AST, glucose and HOMA-IR. Conclusion. Our data suggest that serum HCY levels are lower in NASH compared with NAFL patients and can independently predict NASH. Serum HCY might represent another non-invasive marker for the assessment of NAFLD.
Cumulative Cardiovascular Disease Risk and Triglycerides Differentially Relate to Subdomains of Executive Function in Bipolar Disorder; preliminary findings.
Van Rheenen Tamsyn E,McIntyre Roger S,Balanzá-Martínez Vicent,Berk Michael,Rossell Susan L
Journal of affective disorders
OBJECTIVES:Cardiovascular disease is disproportionally prevalent in bipolar disorder (BD) and has been linked to cognition in preliminary studies. Herein we evaluate the association between known risk factors for cardiovascular disease and executive function in BD patients compared to healthy controls. METHODS:In a sample of n=57 individuals (n=23 BD, n=34 controls) we assessed two subdomains of executive function; cognitive flexibility (using the Trail Making Test - Part B) and cognitive inhibition (using the Stroop Colour Word Interference Task). Cardiovascular risk was assessed by means of serum triglyceride levels, body mass index (BMI) and waist circumference, as well as dietary saturated fat intake and a sex-specific cumulative cardiovascular risk score calculated using the Framingham Heart Study method. RESULTS:Patients with BD had higher BMI and waist circumference, with more BD patients categorized as having central obesity than controls. In the BD group only, higher triglyceride levels were associated with worse cognitive flexibility, and elevated cumulative cardiovascular disease risk was associated with worse cognitive inhibition. No correlations between cardiovascular risk factors and executive function were evident in the control group. LIMITATIONS:The study was limited by the small sample size and should be considered hypothesis-generating CONCLUSIONS: The associations between triglyceride levels, cumulative cardiovascular disease risk and executive functioning evident in BD in this study preliminarily indicate the potential for mechanistic overlap of physical health and cognitive function in the disorder.
10.1016/j.jad.2020.09.104
Elevated triglycerides are associated with decreased executive function among adolescents with bipolar disorder.
Naiberg M R,Newton D F,Collins J E,Dickstein D P,Bowie C R,Goldstein B I
Acta psychiatrica Scandinavica
OBJECTIVE:Cardiovascular risk factors that comprise metabolic syndrome (MetS) have been linked with cognition in adults with bipolar disorder (BD). This study examines the association between MetS components and executive function in adolescents with BD. METHODS:A total of 34 adolescents with BD and 35 healthy control (HC) adolescents were enrolled. MetS components included triglycerides, high-density lipoprotein, glucose, waist circumference, and systolic and diastolic blood pressure. Executive functioning was measured using the intra-extra-dimensional (IED) set-shifting task from the Cambridge Neuropsychological Tests Automated Battery. RESULTS:Adolescents with BD were more likely to have ≥1 MetS components (64.7%) as compared to HC participants (22.9%, χ(2) = 12.29, P = <0.001). Adolescents with BD also had poorer IED task performance compared to HC adolescents (composite Z-score: 0.21 ± 0.52 vs. 0.49 ± 0.51, P = 0.011). Within the BD group, IED composite Z-scores were correlated with diastolic blood pressure and triglyceride levels (ρ = -0.358, P = 0.041 and ρ = -0.396, P = 0.020 respectively). The association of triglycerides with executive function remained significant after controlling for age, IQ, and current use of second-generation antipsychotics. CONCLUSION:Elevated triglycerides are associated with poorer executive function among adolescents with BD. Studies of behavioural and pharmacological interventions targeting MetS components for the purpose of improving executive function among adolescents with BD are warranted.
10.1111/acps.12603
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
Comparison of blood lipid profile/thyroid function markers between unipolar and bipolar depressed patients and in depressed patients with anhedonia or suicidal thoughts.
Su Meilei,Li Enze,Tang Chong,Zhao Yongzhi,Liu Ruqing,Gao Keming
Molecular medicine (Cambridge, Mass.)
BACKGROUND:This study aimed to investigate the differences in the serum levels of glucose, lipid, and thyroid function markers between unipolar and bipolar depressed patients, as well as the effect of anhedonia and suicidal thoughts on the levels of these biochemical parameters. METHODS:A total of 287 unmedicated depressed patients from January 2016 to December 2017 were included in this study, including 92 bipolar depressions and 195 unipolar depressions. Anhedonia was determined using the item 32 of Symptom Checklist (SCL-90). Suicide ideation was assessed by item 15 of SCL-90. RESULTS:The bipolar group had significantly lower lipid levels (including triglycerides, cholesterol, low-density lipoprotein cholesterol [LDL], very low-density lipoprotein cholesterol [VLDL]) and insulin resistance index but higher levels of prolactin, low triiodothyronine (T3) and free T3 (FT3) as well as higher incidence of anhedonia as compared with the unipolar group. Depressed patients with anhedonia had significantly higher LDL level than those without anhedonia. Depressed patients with suicidal thoughts had cholesterol and high-density lipoprotein cholesterol (HDL) level. The above-mentioned differences were confirmed by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) ranged from 0.546 to 0.685. CONCLUSION:Triglycerides, cholesterol, LDL, VLDL T3, FT3 levels were significantly different between unipolar and bipolar depressed patients, which might have the potential to be the markers for differential diagnosis. Patients with anhedonia had lower LDL level, while patients with suicidal thoughts had higher levels of cholesterol and HDL as compared with the corresponding control groups.
10.1186/s10020-019-0119-9
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
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
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
Association of chronic liver disease with depression: a population-based study.
Lee Keanu,Otgonsuren Munkhzul,Younoszai Zahra,Mir Heshaam M,Younossi Zobair M
Psychosomatics
OBJECTIVE:Chronic liver diseases (CLD) have been associated with depression. Our aim was to assess the association of different types of CLD with depression in a population-based cohort. METHODS:We examined data from National Health and Nutrition Examination Survey (NHANES 2005-2010). We included adult patients with chronic hepatitis C (CH-C), chronic hepatitis B (CH-B), alcohol-related liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Patient Health Questionnaire (PHQ-9) survey was used as a depression screener. Univariate and multivariate analyses were performed to determine independent variables associated with each type of CLD and depression. RESULTS:The cohort included 10,231 NHANES participants. After multivariate analysis, CH-C was independently associated with age (OR = 1.05, 95% CI: 1.03-1.07), male gender (OR = 1.88, 95% CI: 1.19-2.97), African American race/ethnicity (OR = 2.50, 95% CI:1.50-4.18), smoking (OR = 6.20, 95% CI: 1.62-23.68), injection drug use (OR = 52.86, 95% CI:32.87-85.03), and depression (OR = 2.87, 95% CI: 1.78-4.62). CH-B was independently associated with being non-Caucasian (for African Americans OR = 5.09, 95% CI: 2.41-10.76, for other races OR = 4.74, 95% CI: 2.32-9.70). ALD was independently associated with younger age (OR = 0.98, 95% CI: 0.96-0.99), male gender (OR = 1.53, 95% CI: 1.19-1.95), Mexican American race/ethnicity (OR = 2.63, 95% CI: 1.87-3.69), and moderate to heavy smoking (OR = 2.08, 95% CI: 1.46-2.96). Finally, presence of insulin resistance [OR = 2.65 95% CI: 1.98-3.55], diabetes [OR = 1.54 95% CI: 1.11-2.13], and Mexican American race/ethnicity [OR = 2.03(1.35-3.06)], were predictive of NAFLD. CONCLUSIONS:Although depression has been suspected to be associated with a number of CLD, this association remains strong only for CH-C.
10.1016/j.psym.2012.09.005
Associations of depression, anxiety and antidepressants with histological severity of nonalcoholic fatty liver disease.
Youssef Nagy A,Abdelmalek Manal F,Binks Martin,Guy Cynthia D,Omenetti Alessia,Smith Alastair D,Diehl Anna Mae E,Suzuki Ayako
Liver international : official journal of the International Association for the Study of the Liver
BACKGROUND:Depression and anxiety are common in patients with nonalcoholic fatty liver disease (NAFLD). However, their associations with histological severity of NAFLD are unknown. AIM:This study examined the association(s) of depression, anxiety and antidepressant pharmacotherapy with severity of histological features in patients with NAFLD. METHODS:We analysed 567 patients with biopsy-proven NAFLD enrolled in the Duke NAFLD Clinical Database. Depressive and anxiety symptoms were assessed using the Hospital Anxiety & Depression Scale (HADS). The associations of depression and anxiety with severity of histological features of NAFLD were analysed using multiple logistic (or ordinal logistic) regression models with and without adjusting for confounding factors. RESULT:Subclinical and clinical depression was noted in 53% and 14% of patients respectively. Subclinical and clinical anxiety was noted in 45% and 25% of patients respectively. After adjusting for confounders, depression was significantly associated with more severe hepatocyte ballooning in a dose-dependent manner (likelihood ratio test, P = 0.0201); adjusted cumulative odds ratio (COR) of subclinical and clinical depression for having a higher grade of hepatocyte ballooning were 2.1 [95% CI, 1.0, 4.4] and 3.6 [95% CI, 1.4, 8.8]. CONCLUSIONS:In patients with NAFLD, depression was associated with more severe hepatocyte ballooning. Further investigation exploring pathobiological mechanisms underlying the observed associations and potential effects of antidepressant pharmacotherapy on NAFLD liver histology is warranted.
10.1111/liv.12165
Non-alcoholic fatty liver disease comorbid with major depressive disorder: The pathological features and poor therapeutic efficacy.
Tomeno Wataru,Kawashima Keigo,Yoneda Masato,Saito Satoru,Ogawa Yuji,Honda Yasushi,Kessoku Takaomi,Imajo Kento,Mawatari Hironori,Fujita Koji,Saito Satoru,Hirayasu Yoshio,Nakajima Atsushi
Journal of gastroenterology and hepatology
BACKGROUND AND AIM:Major depressive disorder (MDD) is an important public health problem, and it is often comorbid with many chronic diseases. The purpose of this study was to identify the clinical features of non-alcoholic fatty liver disease (NAFLD) patients comorbid with MDD and to investigate the influence of MDD on the effect of treatment in patients with NAFLD. METHODS:A total of 258 patients with biopsy-proven NAFLD were included. MDD was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. The patients were followed up for 48 weeks under standard care for NAFLD, which consisted mainly of lifestyle modification. RESULTS:There were 32 patients comorbid with MDD. They were characterized by more severe histological steatosis and higher NAFLD activity score, and also significantly higher levels of serum aminotransferase, γ-glutamyl transpeptidase and ferritin, than age-and-sex-matched NAFLD patients without MDD. Moreover, NAFLD patients with MDD showed poor response to the standard care for NAFLD, in body weight loss and in other parameters. Particularly, NAFLD patients with unstable MDD (not in full/partial remission) showed severe resistance to the treatment. CONCLUSION:This is the first study to demonstrate the clinical features and response to therapy of NAFLD patients comorbid with MDD. The comorbid state of MDD was associated with more severe histological liver steatosis and worse treatment outcomes in patients with NAFLD. Further investigations are required to develop new lifestyle modification programs that enable NAFLD patients with MDD to achieve the treatment goal.
10.1111/jgh.12897
Non-Alcoholic Fatty Liver Disease and Its Association with Depression in Korean General Population.
Jung Ju Young,Park Sung Keun,Oh Chang Mo,Chung Pil Wook,Ryoo Jae Hong
Journal of Korean medical science
BACKGROUND:Recent studies have indicated the significant association between non-alcoholic fatty liver disease (NAFLD) and depression. However, there is ongoing debate on whether the risk for depression is actually related with the presence and severity of NAFLD. Thus, this study was conducted to investigate the association between depression and NAFLD evaluated by diverse modalities. METHODS:A total of 112,797 participants from the Korean general population were enrolled. The study participants were categorized into three groups according to degree of NAFLD evaluated by ultrasonography, fatty liver index (FLI) and fibrosis-4 score (FIB-4). Depression was defined as a score of Center for Epidemiological Studies-Depression (CES-D) ≥ 16, and the odd ratios (ORs) and 95% confidence interval (CI) for depression (adjusted ORs [95% CI]) were assessed by multiple logistic regression analyses. RESULTS:In the unadjusted model, the presence and severity of NAFLD was not significantly associated with depressive symptoms. However, in the fully adjusted model, ORs for depression increased in proportion to the degree of ultrasonographically detected NAFLD (mild fatty liver: 1.14 [1.06-1.22]; and moderate to severe fatty liver: 1.32 [1.17-1.48]). An association was also observed between depression and FLI (30 ≤ FLI < 60: 1.06 [0.98-1.15]; FLI ≥ 60: 1.15 [1.02-1.29]). CONCLUSION:The presence and severity of NAFLD is significantly associated with depressive symptoms. In addition, this association was more distinct after adjusting for covariates including age, gender and insulin resistance. This finding indicates the necessity of further study evaluating the incidental relationship of depression with NAFLD.
10.3346/jkms.2019.34.e199
Interaction Mechanisms Between Major Depressive Disorder and Non-alcoholic Fatty Liver Disease.
Shao Qi,Wu Yiping,Ji Jing,Xu Tian,Yu Qiaoyu,Ma Chongyang,Liao Xuejing,Cheng Fafeng,Wang Xueqian
Frontiers in psychiatry
Major depressive disorder (MDD), which is highly associated with non-alcoholic fatty liver disease (NAFLD), has complex pathogenic mechanisms. However, a limited number of studies have evaluated the mutual pathomechanisms involved in MDD and NAFLD development. Chronic stress-mediated elevations in glucocorticoid (GC) levels play an important role in the development of MDD-related NAFLD. Elevated GC levels can induce the release of inflammatory factors and changes in gut permeability. Elevated levels of inflammatory factors activate the hypothalamic-pituitary-adrenal (HPA) axis, which further increases the release of GC. At the same time, changes in gut permeability promote the release of inflammatory factors, which results in a vicious circle among the three, causing disease outbreaks. Even though the specific role of the thyroid hormone (TH) in this pathogenesis has not been fully established, it is highly correlated with MDD and NAFLD. Therefore, changing lifestyles and reducing psychological stress levels are necessary measures for preventing MDD-related NAFLD. Among them, GC inhibitors and receptor antagonists may be key in the alleviation of early and mid-term disease progression. However, combination medications may be important in late-stage diseases, but they are associated with various side effects. Traditional Chinese medicines have been shown to be potential therapeutic alternatives for such complex diseases.
10.3389/fpsyt.2021.711835
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
High prevalence of metabolic disturbances in patients with bipolar disorder in Taiwan.
Chang Hui Hua,Chou Chen Hsi,Chen Po See,Gean Po Wu,Huang Hui Chun,Lin Chia Yin,Yang Yen Kuang,Lu Ru Band
Journal of affective disorders
BACKGROUND:Both ethnicity and lifestyle may contribute to these abnormalities. High prevalences of obesity and metabolic disturbances in patients with bipolar disorder (BD) have been reported in western countries. However, reports about the prevalences in Asian countries remain scant. METHOD:The cross-sectional study included 117 patients diagnosed as BD and treated with lithium (Li), valproate (VPA), or both at a university psychiatric outpatient clinic. Their body mass index and plasma levels of glucose and lipid were measured. The prevalence of metabolic syndrome was determined based on the IDF 2005 criteria. RESULTS:13.7%, 36.8%, 53.0%, 18.6%, and 61.0% of the patients met the criteria for hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension and large waist circumference, respectively. 33.9% of the patients met the IDF 2005 criterion for metabolic syndrome. The prevalence of metabolic abnormalities was significantly higher in patients who have been cotreated with second-generation antipsychotics (SGAs). CONCLUSION:This study provides evidence of high prevalence of metabolic syndrome in BD patients in Taiwan. Such metabolic disturbances can increase morbidity and mortality. Further studies that focus on the underlying mechanisms and effective intervention strategies are warranted.
10.1016/j.jad.2008.12.018
The role of valproate in metabolic disturbances in bipolar disorder patients.
Chang Hui Hua,Yang Yen Kuang,Gean Po Wu,Huang Hui Chun,Chen Po See,Lu Ru Band
Journal of affective disorders
BACKGROUND:Our previous report showed that patients with bipolar disorder (BD) have higher prevalence of hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL) and obesity in Taiwan. To confirm whether the metabolic disturbances is associated with the disease itself or the medications used for treating BD, we further compared the metabolic status among the valproate (VPA) treated BD patients, drug-free BD patients and healthy controls in Taiwan. METHOD:This cross-sectional study included 119 healthy controls and 77 BD patients diagnosed according to the DSMIV-TR criteria in a university hospital. Among the diseased group, 25 remitted BD patients were drug-free (BD-F), and 52 of them were treated with VPA (BD-VPA). Their body mass index (BMI), plasma glucose levels and plasma lipid profiles were measured. RESULTS:Plasma fasting glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL) levels were significantly different among BD-VPA, the BD-F, and the healthy control groups. Valproate treatment was associated with significant higher plasma insulin, triglyceride, and BMI levels as well as lower fasting glucose and HDL levels. However, these biochemical indexes did not differ significantly between the BD-F and the healthy control groups. CONCLUSION:These results provide further evidence that VPA treatment for BD may increase the risk of metabolic disturbances. The risk may be reduced after discontinuing VPA medication.
10.1016/j.jad.2009.12.011
Age-specific prevalence of metabolic syndrome in Italian patients with bipolar disorder.
Salvi Virginio,D'Ambrosio Virginia,Rosso Gianluca,Bogetto Filippo,Maina Giuseppe
Psychiatry and clinical neurosciences
AIM:Metabolic syndrome (MetS) is highly prevalent in patients with bipolar disorder (BD). Little research has evaluated the risk profile of MetS and cardiovascular disease in different gender and age groups in these patients. Our aim is to evaluate the prevalence of MetS in Italian patients with BD stratified by gender and age, and to determine the correlates of MetS. METHODS:Subjects with BD were included and stratified by sex and age according to the following age groups: <30; 30-39; 40-49; 50-59; ≥ 60 years. Socio-demographic and clinical characteristics, lifestyle information, and comorbidity for cardiovascular diseases and diabetes were collected. MetS was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. RESULTS:MetS was evaluated in 200 patients, with a prevalence of 26.5%. Men had higher rates of hypertension and hypertriglyceridemia, women had more abdominal obesity. Women had a peak of prevalence in the ≥ 60 years group, while men displayed high rates even in the young age groups. In young patients, MetS was associated with Cluster B personality disorders and less physical exercise. CONCLUSION:Our paper highlights the importance of evaluating MetS even in young patients with bipolar disorder, especially males. The strong association with lack of physical exercise suggests that the implementation of healthy behaviors might be relevant in order to prevent MetS and future adverse cardiovascular outcomes.
10.1111/j.1440-1819.2010.02160.x
General medical conditions in 347 bipolar disorder patients: clinical correlates of metabolic and autoimmune-allergic diseases.
Perugi Giulio,Quaranta Giuseppe,Belletti Serena,Casalini Francesca,Mosti Nicola,Toni Cristina,Dell'Osso Liliana
Journal of affective disorders
BACKGROUND:Patients with bipolar disorder (BD) suffer from greater physical morbidity and mortality than the general population. The aim of the present study is to explore the prevalence and clinical correlates of General Medical Conditions (GMC) in a large consecutive sample of patients with BD. METHOD:The study sample comprised of 347 patients who met DSM-IV-TR criteria for BD I (n=207, 59.7%), BD II or Cyclothymic Disorder (n=140, 40.3). Diagnostic information was collected by means of the Structured Clinical Interview for DSM-IV Axis I Disorders- Clinical Version (SCID-I), and information about personal and family history were collected by the Semi-Structured Interview for Mood Disorder-Revised (SIMD-R). Standardized procedure was used to assess the diagnosis of GMC, which was considered present only if a specific therapy to treat the condition was prescribed by a specialist or a general practitioner. In order to explore possible relationships between physical comorbidity and clinical features of BD, we compared patients with (MD) and without (No-MD) Metabolic Diseases (MD) and patients with (AAD) and without (No-AAD) Autoimmune-Allergic Diseases (AAD). RESULTS:The most commonly reported GMCs were: Headache, Hypercholesterolemia (>200mg/dl), Chronic Constipation, Obesity, Arterial Hypertension (BP >140/90 mmHg), Hypothyroidism, Allergic Rhino-Conjunctivitis, Irritable Bowel Syndrome, Hypertriglyceridemia (>150 mg/dl), Metabolic Syndrome, Hiatus Hernia, Dysmenorrhea, Urticaria, Atopic Dermatitis, Psoriasis, Seborrheic Dermatitis, Diabetes Mellitus, Bronchial Asthma, Cardiac Arrhythmias, Biliary Lithiasis, and COPD. In our sample, MD (n=148, 42.7%) and AAD (n=167, 48.1%) were the most common categories of GMCs. Interestingly, the lifetime prevalence of cancer and neoplastic diseases was very low: 1 patient (.3%) reported Lung Adenocarcinoma and 2 (.6%) patients Bowel Cancer. In the group comparisons, length of pharmacological treatment (OR=1.054; 95% CI=1.030-1.078), age at onset of first major episode (OR=1.043; 95% CI=1.019-1.067), length of the current episode (OR=1.025; 95% CI=1.020-1.533) and absence of lifetime comorbid substance abuse (OR=.373; 95% CI=.141-.989) were statistically associated with the presence of comorbid MD; while only AD-induced hypomania (OR=1.62; 95% CI=1.011-2.597), and cyclothymic temperament (OR=1.051; 95% CI=1.016-1.087) were statistically associated with the presence of comorbid AAD. LIMITATIONS:Possible referral and selection bias; retrospective, non-blind, cross-sectional evaluation. CONCLUSION:MD and AAD were highly represented in our sample, while cancer and neoplastic diseases were uncommon. The clinical correlates of different sub-groups of GMC suggest different interpretations. The presence of MD seems to be correlated with the progression of BD and the chronic medication exposure, while comorbid AAD seems to correlate with a specific clinical subtype of BD, characterized by mood reactivity and temperamental mood instability. If the link with autoimmune-allergic diathesis will be confirmed, it could provide an interesting new paradigm for the study of the "systemic" nature of mood disorders and a promising target for future treatment options.
10.1016/j.jad.2014.08.052
Association between hyperuricemia and metabolic syndrome in patients suffering from bipolar disorder.
Chen Jingxu,Chen Hongmei,Feng Junhui,Zhang Ligang,Li Juyan,Li Ran,Wang Shaoli,Wilson Ian,Jones Alison,Tan Yunlong,Yang Fude,Huang Xu-Feng
BMC psychiatry
BACKGROUND:Clinical studies have shown that bipolar patients have increased serum uric acid levels. High serum uric acid levels could play a role contributing to high prevalence of metabolic syndrome. Metabolic syndrome is known to increase the risk of developing a number of life threatening diseases including coronary heart disease, hypertension, and type 2 diabetes. This study investigated the association between hyperuricemia and metabolic syndrome and its components in individuals suffering from bipolar disorders. METHODS:This study recruited 318 inpatients suffering from bipolar disorders from Beijing Hui-Long-Guan Hospital in China and 160 healthy subjects from the same region as the controls. We used National Cholesterol Education Program Adult Treatment Panel III Adapted criteria (NCEP ATP-III A) for the diagnosis of metabolic syndrome. Hyperuricemia was determined as serum uric acid level above 420 μmol/L in men and 360 μmol/L in women (N Engl J Med 359(17):1811-1821, 2008). RESULTS:Among 318 bipolar patients, there was higher prevalence of metabolic syndrome (42.5%) and hyperuricemia (27.7%) than healthy controls (21.9 and 11.9%). Bipolar patients with metabolic syndrome had increased prevalence of hyperuricemia (OR = 3.0, CI95 [1.7-5.4]). Hypertriglyceridemia and larger waist circumference (WC) were associated with hyperunicemia (OR = 1.8, CI95 [1.1-3.1], OR = 1.9, CI95 [1.1-3.4]). Hyperuricemia was associated with metabolic syndrome in bipolar patients (p < 0.001) and especially with hypertriglyceridemia (OR = 1.9, CI95 [1.1-3.1] and increased WC (OR = 2.1 [1.2-4.0]). Bipolar patients over 50 years of age and hyperuricemia were highly prone to develop metabolic syndrome (OR = 14.0, CI95 [5.0-39.0]). CONCLUSIONS:Hyperuricemia was highly associated with development of metabolic disorder particularly for aged patients suffering from bipolar disorders. Early prevention of hyperuricemia and metabolic syndrome may lead better life for bipolar patients when they get older.
10.1186/s12888-018-1952-z
Prevalence of metabolic syndrome and its clinical correlates among patients with bipolar disorder.
Kumar Ajay,Narayanaswamy Janardhanan C,Venkatasubramanian G,Raguram R,Grover Sandeep,Aswath Manju
Asian journal of psychiatry
OBJECTIVE:To assess the prevalence of metabolic syndrome (MetS) in patients with bipolar disorder (BD) and examine the clinical correlates of MetS. METHODS:Sixty-seven patients with BD were evaluated for presence for MetS. The consensus definition was used to define MetS. The clinical variables were recorded on the basis of information provided by the patients, accompanying caregivers and review of treatment records. The symptoms severity of present depressive and manic episode was assessed by using Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) respectively. RESULTS:The prevalence of MetS was 53.7%. Patients with MetS were older than the patients with BD alone (P=0.001). Increased waist circumference was the most common abnormal parameter (74.6%) followed by low high density lipoprotein (HDL) (71.6%) and raised triglycerides (64.2%). High blood pressures were recorded in 35.8% with high fasting blood glucose levels were seen in 33.3%. MetS was associated with greater number of life time episodes (p=0.010), longer duration of illness (p=0.010), greater numbers of lifetime depressive episodes (p<0.001). Substance use (alcohol and nicotine) associated with significantly higher prevalence of high blood pressure among MetS patients (p<0.001) while abnormal triglyceride level shown associated with substance use (p=0.010). Age of the patients, number of lifetime depressive episodes and use of Olanzapine were found to predictive of the development of MetS. CONCLUSIONS:Patients with BD have high prevalence of MetS and its presence correlates with clinical variables.
10.1016/j.ajp.2017.01.020
Association between abnormal glycolipid level and cognitive dysfunction in drug-naïve patients with bipolar disorder.
Qiu Yan,Li Sujuan,Teng Ziwei,Tan Yuxi,Xu Xuelei,Yang Min,Zhao Ziru,Liu Jieyu,Tang Hui,Xiang Hui,Chen Jindong,Wang Bolun,Wu Haishan
Journal of affective disorders
OBJECTIVES:Cognitive impairment and abnormal glycolipid metabolism are common clinical features of bipolar disorder (BD). The purpose of this study was to investigate the relationship between conventional glycolipid metabolism indicators and cognitive impairment in patients with BD. METHODS:A total of 132 drug-naïve patients with BD and 129 healthy controls (HC) were recruited in the study. Five serum glycolipid metabolism indicators were measured and cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test) for each participant. RESULTS:The scores of immediate memory, attention, language and delayed memory in BD group were significantly lower than those in HC group (P < 0.05). The triglyceride (TG) level in BD group was higher than that in HC group (P = 0.011), and the total cholesterol and high-density lipoprotein cholesterol (HDL) levels were lower than those in HC group (P = 0.026; P = 0.001). Regression analysis showed that TG level was significantly correlated with RBANS total score (β = 0.245, P = 0.008), attention (β = 0.289, P = 0.03) and delayed memory (β = 0.221, P = 0.023). Fasting blood glucose (FBG) level was significantly correlated with language subscale score (β = -0.187, P = 0.046) in BD. LIMITATIONS:Cross-sectional design and limited control variables. CONCLUSIONS:Elevated FBG and TG levels may be associated with cognitive dysfunction in BD patients. Improving glycolipid metabolism in patients with BD may help to improve certain domain-specific cognitive functions.
10.1016/j.jad.2021.10.100
Etiology Exploration of Non-alcoholic Fatty Liver Disease From Traditional Chinese Medicine Constitution Perspective: A Cross-Sectional Study.
Zhu Ke,Guo Yongsong,Zhao Chenghao,Kang Shixin,Li Jialiang,Wang Jiexin,Tang Zhaohui,Lin Bing,Li Weihong
Frontiers in public health
From the traditional Chinese medicine (TCM) constitution theory perspective, the phlegm-dampness constitution is thought to be closely related to the occurrence of non-alcoholic fatty liver disease (NAFLD). However, this viewpoint still lacks rigorous statistical evidence. This study aimed to test the association between the phlegm-dampness constitution and NAFLD. We conducted a cross-sectional study. Participants were residents living in Chengdu, China, undergoing health checkups at the health management center of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between December 2018 and September 2020. TCM constitution type was diagnosed by DAOSH four examinations instrument, NAFLD was diagnosed according to the liver ultrasonography and medical history. Multivariate logistic regression and propensity score matching (PSM) were used to analyze a total of 1,677 qualified data. 1,037 participants had biased constitution(s), 67.8% of which had mixed constitutions (with at least two constitutions). Among 1,677 participants, the phlegm-dampness constitution was associated with the yang-deficiency, yin-deficiency, dampness-heat, qi-depression, and blood-stasis constitutions. The correlation coefficients were 0.11, 0.32, 0.42, 0.20, 0.14, respectively. Between the phlegm-dampness constitution and NAFLD, the odds ratio (OR) and the 95% confidence interval (CI) was 2.05 (1.57-2.69) in the crude model. After adjusting for age, gender, Body mass index (BMI), other biased constitutions, smoking, high blood pressure, diabetes, and dyslipidemia, the OR reduced to 1.51 (1.04-2.18). The associations of seven other biased TCM constitutions and NAFLD were not statistically significant in the fully adjusted model. The PSM analysis showed consistent results with the logistic regression. Among eight biased TCM constitutions, the phlegm-dampness constitution is independently associated with NAFLD. We speculate the phlegm-dampness constitution is a risk factor of NAFLD. Longitudinal studies are needed to confirm this causal relationship in the future. In addition, inconsistent with some TCM practitioners' experience, we disagree that the blood-stasis constitution is associated with NAFLD.
10.3389/fpubh.2021.635818
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
Gut Microbiota, Glucose, Lipid, and Water-Electrolyte Metabolism in Children With Nonalcoholic Fatty Liver Disease.
Pan Xiongfeng,Kaminga Atipatsa C,Liu Aizhong,Wen Shi Wu,Luo Miyang,Luo Jiayou
Frontiers in cellular and infection microbiology
There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota, glucose, and lipid. However, the function of water-electrolyte metabolism remains undefined in children with NAFLD. Therefore, the aim of this case-control study was to better understand these interactions. The sample consisted of 75 children, aged between 7 and 16, of whom 25 had nonalcoholic fatty liver (NAFL), 25 had nonalcoholic steatohepatitis (NASH), and 25 were obese and without NAFLD. These groups were matched by age, sex, and body mass index. Data were collected between June, 2019 and December, 2019 at the Hunan Children's Hospital, in China. Microbiome composition in fecal samples was assessed using 16S ribosomal RNA amplicon sequencing. In the clinical indices, 12 glucose and lipid metabolism indices were included, and six water-electrolyte metabolism indices were included. The results indicated that microbiomes of NAFLD children had lower alpha diversity but higher beta diversity index than the other two groups. Specifically, anti-inflammatory and probiotics abundance (e.g., , , and ) was significantly decreased in NAFLD, whereas the abundance of harmful bacteria (e.g., ) was increased. Moreover, the abundance of butyrate-producing bacteria (e.g., , , , and ) was significantly decreased in NASH. The abundance of these bacteria were associated with glucose, lipid, and water-electrolyte metabolism (e.g., glucose, triglyceride, cholesterol, inorganic salt, total body water, etc.), implying that the NAFLD and its severity were associated with glucose, lipid, and water-electrolyte metabolism dysbiosis. Therefore, these findings suggest that the gut microbiome, especially butyrate-producing bacteria, play an important role in the development of NAFLD in children.
10.3389/fcimb.2021.683743
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
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
Obesity, altered oxidative stress, and clinical correlates in chronic schizophrenia patients.
An Huimei,Du Xiangdong,Huang Xingbing,Qi Lingyan,Jia Qiufang,Yin Guangzhong,Xiao Chunling,Huang Xu-Feng,Ning Yuping,Cassidy Ryan M,Wang Li,Soares Jair C,Zhang Xiang Yang
Translational psychiatry
Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p < 0.05) were independent contributors to the BMI in patients. These results suggested that oxidative stress may play an important role in antipsychotic-induced weight gain. Further investigations using the longitudinal design in first-episode schizophrenia patients are needed to explore the beneficial effect of antioxidants on the abnormal lipid metabolism mediated by antipsychotic treatment.
10.1038/s41398-018-0303-7
The prevalence, risk factors, and clinical characteristics of insulin resistance in Chinese patients with schizophrenia.
Lin Chen,Chen Ke,Zhang Rongzhen,Fu Weihong,Yu Jianjin,Gao Lan,Ni Haiqing,Song Jiaqi,Chen Dachun
Comprehensive psychiatry
BACKGROUND:Studies have shown that patients with schizophrenia are at a high risk of developing insulin resistance (IR). We investigated the prevalence of IR and its clinical correlates in hospitalized Chinese patients with schizophrenia. METHODS:A total of 193 patients with schizophrenia (113 males and 80 females) were recruited for the study. We collected their demographic and clinical data, including data on their plasma glucose and lipid levels. All patients were rated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognitive function, while Positive and Negative Syndrome Scale (PANSS) was used to assess psychopathology. The cut-off value for the homeostasis model assessment of insulin resistance (HOMA-IR) was set at 1.7. RESULTS:The prevalence of IR was 37.82% (73/193). The IR patients had significantly higher waist-to-hip ratio and body mass index (BMI), and higher fasting plasma glucose (FPG), triglyceride (TG), and low density lipoprotein (LDL) levels compared to non-IR patients (all p<.05). Binary logistic regression analysis showed that smoking, BMI, and TG and LDL levels are significant predictors of IR. In addition, correlation analysis showed that IR was significantly correlated with the waist-to-hip ratio, BMI, and LDL level (Bonferroni corrected p<.05). The multivariable linear regression analysis indicated that the BMI and FPG are associated with the IR index. There was no significant difference in IR index between patients who were taking different antipsychotics. CONCLUSION:We found a high prevalence of IR and its risk factors in Chinese patients with schizophrenia. Active weight control to reduce the BMI and waist circumference and reducing the number of cigarettes consumed, may be essential to decrease the incidence of IR in patients with schizophrenia.
10.1016/j.comppsych.2019.152145
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
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 Intestinal Microbiome in Nonalcoholic Fatty Liver Disease.
Puri Puneet,Sanyal Arun J
Clinics in liver disease
Nonalcoholic fatty liver disease is the most common cause of chronic liver disease in North America and is growing as a cause of chronic liver disease in many other parts of the world as well. It has 2 principal clinical-pathologic phenotypes: (1) nonalcoholic fatty liver and (2) nonalcoholic steatohepatitis. The development of both phenotypes is tightly linked to excess body weight and insulin resistance. This review discusses the emerging tools for the analysis of the microbiome, their limitations, and the existing literature with respect to the intestinal microbiome and their role in nonalcoholic fatty liver.
10.1016/j.cld.2017.08.009
and ameliorate progression of non-alcoholic fatty liver disease through modulation of the gut microbiome.
Lee Na Young,Yoon Sang Jun,Han Dae Hee,Gupta Haripriya,Youn Gi Soo,Shin Min Jea,Ham Young Lim,Kwak Min Jung,Kim Byung Yong,Yu Jeong Seok,Lee Do Yup,Park Tae-Sik,Park Si-Hyun,Kim Byoung Kook,Joung Hyun Chae,Choi In Suk,Hong Ji Taek,Kim Dong Joon,Han Sang Hak,Suk Ki Tae
Gut microbes
Targeting the gut-liver axis by modulating the gut-microbiome can be a promising therapeutic approach in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of single species and a combination of and in NAFLD mice model. Six-week male C57BL/6J mice were divided into 9 groups (n = 10/group; normal, Western diet, and 7 Western diet-strains [10 CFU/g, 8 weeks]). The strains used were KID7, and three combinations (1: , 2: KID7, and 3: ). Liver/Body weight ratio, serum and stool analysis, liver pathology, and metagenomics by 16S rRNA-sequencing were examined. In the liver/body ratio, (5.1 ± 0.5), (5.2 ± 0.4), KID7 (5.5 ± 0.5), and combination1 and 2 (4.2 ± 0.6 and 4.8 ± 0.7) showed significant reductions compared with Western (6.2 ± 0.6)(p < 0.001). In terms of cholesterol and steatosis/inflammation/NAFLD activity, all groups except for were associated with an improvement ( < .05). The elevated level of tumor necrosis factor-α/interleukin-1β (pg/ml) in Western (65.8 ± 7.9/163.8 ± 12.2) was found to be significantly reduced in (24.2 ± 1.0/58.9 ± 15.3), (35.6 ± 2.1/62.9 ± 6.0), (43.4 ± 3.2/53.6 ± 7.5), and KID7 (22.9 ± 3.4/59.7 ± 12.2)(p < 0.01). Cytokines were improved in the combination groups. In metagenomics, each strains revealed a different composition and elevated / ratio in the western (47.1) was decreased in (14.5), (3.0), and KID7 (13.3). , and KID7 supplementation can improve NAFLD-progression by modulating gut-microbiome and inflammatory pathway.
10.1080/19490976.2020.1712984
Gut Microbiota and Bipolar Disorder: An Overview on a Novel Biomarker for Diagnosis and Treatment.
Lucidi Lorenza,Pettorruso Mauro,Vellante Federica,Di Carlo Francesco,Ceci Franca,Santovito Maria Chiara,Di Muzio Ilenia,Fornaro Michele,Ventriglio Antonio,Tomasetti Carmine,Valchera Alessandro,Gentile Alessandro,Kim Yong-Ku,Martinotti Giovanni,Fraticelli Silvia,Di Giannantonio Massimo,De Berardis Domenico
International journal of molecular sciences
The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut-brain-microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD.
10.3390/ijms22073723
Prevalence of liver disease in veterans with bipolar disorder or schizophrenia.
Fuller Bret E,Rodriguez Veronica L,Linke Alex,Sikirica Mirko,Dirani Riad,Hauser Peter
General hospital psychiatry
OBJECTIVE:To assess the prevalence of three liver diseases [hepatitis C virus (HCV), nonalcoholic fatty liver disease and alcohol-induced cirrhosis] in patients (veterans) with/without schizophrenia/schizoaffective disorder and bipolar disorder. METHODS:A retrospective electronic chart review of Veterans Integrated Services Network 20 facilities from January 1, 2001 to December 21, 2006 selected patients to one of two groups: schizophrenia/schizoaffective disorder or bipolar disorder. Patients in both groups were compared with veterans in an equal-sized random sample from the same data set of veterans without psychiatric diagnoses. Logistic regression models evaluated risk for overall liver diseases as well as HCV, nonalcoholic fatty liver disease and alcoholic-induced cirrhosis. RESULTS:Patients with schizophrenia (n=6521) had a higher prevalence of liver disease [22.4% versus 3.2%; odds ratio (OR)=8.73]; HCV (16.5% versus 1.9%; OR=10.21); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=4.09) than matched controls. Patients with bipolar disorder (n=5319) had a higher prevalence of liver disease (21.5% versus 3.5%; OR=7.58); HCV (15.5% versus 2.1%; OR=8.60); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=3.82) than matched controls. Risk factors for liver disease in patients with schizophrenia (versus matched controls) included diabetes (OR=1.29), hypertension (OR=1.27), HIV (OR=3.54), substance use disorder (SUD) (OR=2.28), alcohol use disorder (OR=3.05) and schizophrenia (OR=2.74). Risk factors for development of liver disease for patients with bipolar disorder: diabetes (OR=1.40), HIV (OR=3.66), SUD (OR=2.68), alcohol use disorder (OR=3.22) and bipolar disorder (OR=2.27). CONCLUSIONS:This study in veterans shows that the presence of mental illness and its comorbidities represents a significant risk factor for the diagnosis of liver disease, including HCV and alcohol-related cirrhosis.
10.1016/j.genhosppsych.2011.03.006
Patatin-like phospholipase domain-containing protein 3 (PNPLA3): A potential role in the association between liver disease and bipolar disorder.
Kenneson Aileen,Funderburk Jennifer S
Journal of affective disorders
OBJECTIVE:Due to the increased prevalence of liver disease in patients with bipolar disorder, we examined the potential role of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant among individuals with bipolar disorder and those with no mood disorder. METHODS:We used the National Health and Nutrition Examination Survey (NHANES) database (aged 15-39 years) to identify a group of individuals with a bipolar diagnosis and a control group of individuals with no mood disorder. A total of 1931 individuals were randomly selected, one from each family containing information on the PNPLA3 genotype to be used in the analysis. RESULTS:Analyses revealed individuals with the recessive variant genotype (MM) had an adjusted odds ratio for bipolar disorder of about 4.6 compared to individuals with either IM or II genotypes of the PNPLA3 variant. LIMITATIONS AND CONCLUSIONS:Limitations of this study include the use of a lay-administered survey in for diagnosis of bipolar disorder in NHANES. The association between the PNPLA3 variant and bipolar disorder may help guide further work on medication effectiveness, treatment options, prevention approaches, and understanding potential medication side effects among specific subgroups of individuals with the MM genotype.
10.1016/j.jad.2016.11.035
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
Psychosocial outcomes for children with nonalcoholic fatty liver disease over time and compared with obese controls.
Kerkar Nanda,D'Urso Christine,Van Nostrand Kelsey,Kochin Israel,Gault Allison,Suchy Frederick,Miloh Tamir,Arnon Ronen,Chu Jaime,Annunziato Rachel
Journal of pediatric gastroenterology and nutrition
OBJECTIVES:Children with nonalcoholic fatty liver disease (NAFLD) experience compromised quality of life (QOL) akin to those with other chronic disease. Our objectives were to examine the association between NAFLD and QOL as well as other psychosocial outcomes, to compare psychosocial outcomes to obese children without known NAFLD, and to determine whether present standard care for NAFLD results in weight loss and improvement in psychosocial outcomes longitudinally. METHODS:Children with NAFLD between 8 and 18 years and obese control children without known NAFLD were consented to complete a brief psychosocial battery examining depression (Children's Depression Inventory), QOL (Pediatric Quality of Life Inventory; PedsQL), and effect of weight on self-esteem (Body-Esteem Scale for Adolescents and Adults) at baseline; and additionally for the NAFLD group after at least 6 months. RESULTS:A total of 48 children with NAFLD and 40 obese control children were enrolled. The PedsQL scores were not significantly different but the CDI total score and subscales of negative mood, ineffectiveness, and negative self-esteem as well as all of the 3 subscales of BESAA, appearance, attribution, and weight were worse in the NAFLD group compared with obese controls. The PedsQL scores also did not change after standard care in the 33 patients with NAFLD who completed the follow-up evaluations, but the CDI score differed between those whose body mass index improved or not. CONCLUSIONS:Children with NAFLD have higher levels of depression than obese controls. Outcomes did not improve with standard care. Larger longitudinal studies and appropriate interventions are required in this area.
10.1097/MPG.0b013e31826f2b8c
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
Free-breathing fat and R * quantification in the liver using a stack-of-stars multi-echo acquisition with respiratory-resolved model-based reconstruction.
Schneider Manuel,Benkert Thomas,Solomon Eddy,Nickel Dominik,Fenchel Matthias,Kiefer Berthold,Maier Andreas,Chandarana Hersh,Block Kai Tobias
Magnetic resonance in medicine
PURPOSE:To develop a free-breathing hepatic fat and quantification method by extending a previously described stack-of-stars model-based fat-water separation technique with additional modeling of the transverse relaxation rate . METHODS:The proposed technique combines motion-robust radial sampling using a stack-of-stars bipolar multi-echo 3D GRE acquisition with iterative model-based fat-water separation. Parallel-Imaging and Compressed-Sensing principles are incorporated through modeling of the coil-sensitivity profiles and enforcement of total-variation (TV) sparsity on estimated water, fat, and parameter maps. Water and fat signals are used to estimate the confounder-corrected proton-density fat fraction (PDFF). Two strategies for handling respiratory motion are described: motion-averaged and motion-resolved reconstruction. Both techniques were evaluated in patients (n = 14) undergoing a hepatobiliary research protocol at 3T. PDFF and parameter maps were compared to a breath-holding Cartesian reference approach. RESULTS:Linear regression analyses demonstrated strong (r > 0.96) and significant (P ≪ .01) correlations between radial and Cartesian PDFF measurements for both the motion-averaged reconstruction (slope: 0.90; intercept: 0.07%) and the motion-resolved reconstruction (slope: 0.90; intercept: 0.11%). The motion-averaged technique overestimated hepatic values (slope: 0.35; intercept: 30.2 1/s) compared to the Cartesian reference. However, performing a respiratory-resolved reconstruction led to better value consistency (slope: 0.77; intercept: 7.5 1/s). CONCLUSIONS:The proposed techniques are promising alternatives to conventional Cartesian imaging for fat and quantification in patients with limited breath-holding capabilities. For accurate estimation, respiratory-resolved reconstruction should be used.
10.1002/mrm.28280
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
Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches.
BMC medicine
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in over 5% of the parenchyma in the absence of excessive alcohol consumption. It is more prevalent in patients with diverse mental disorders, being part of the comorbidity driving loss of life expectancy and quality of life, yet remains a neglected entity. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and increases the risk for cirrhosis and hepatic carcinoma. Both NAFLD and mental disorders share pathophysiological pathways, and also present a complex, bidirectional relationship with the metabolic syndrome (MetS) and related cardiometabolic diseases. MAIN TEXT:This review compares the demographic data on NAFLD and NASH among the global population and the psychiatric population, finding differences that suggest a higher incidence of this disease among the latter. It also analyzes the link between NAFLD and psychiatric disorders, looking into common pathophysiological pathways, such as metabolic, genetic, and lifestyle factors. Finally, possible treatments, tailored approaches, and future research directions are suggested. CONCLUSION:NAFLD is part of a complex system of mental and non-communicable somatic disorders with a common pathogenesis, based on shared lifestyle and environmental risks, mediated by dysregulation of inflammation, oxidative stress pathways, and mitochondrial function. The recognition of the prevalent comorbidity between NAFLD and mental disorders is required to inform clinical practice and develop novel interventions to prevent and treat these complex and interacting disorders.
10.1186/s12916-020-01713-8