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    The potential association between obesity and bipolar disorder: A meta-analysis. Zhao Zhuoxian,Okusaga Olaoluwa O,Quevedo Joao,Soares Jair C,Teixeira Antonio L Journal of affective disorders BACKGROUND:Several epidemiological studies have found that the prevalence of bipolar disorder (BD) is significantly higher in obese population than non-obese population. However, no meta-analysis has been published to quantitatively summarize the related literature. METHODS:In this study, we conducted a meta-analysis to explore the association between obesity and BD by combining 9 cross-sectional studies with a total of 12,259 BD cases and 615,490 non-BD controls. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled odds ratio (OR), while the heterogeneity was assessed using I(2) and Q statistic. RESULTS:Our meta-analysis suggests that obesity is associated with increased prevalence of BD by a random-effect model (OR=1.77, 95% CI: 1.40-2.23; Q=44.62, P<0.001, I(2)=82.1%). LIMITATION:Without prospective studies, we cannot determine whether obesity increased the risk of developing BD or vice-versa. CONCLUSION:Obesity is positively associated with BD. 10.1016/j.jad.2016.05.059
    Prevalence, clinical characteristics, risk factors, and indicators for lean Chinese adults with nonalcoholic fatty liver disease. Zeng Jing,Yang Rui-Xu,Sun Chao,Pan Qin,Zhang Rui-Nan,Chen Guang-Yu,Hu Ying,Fan Jian-Gao World journal of gastroenterology BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases in the world. Nowadays, the percentage of non-obese or lean patients with NAFLD is increasing. NAFLD in non-obese populations, especially the lean subgroup with a normal waist circumference (WC), might lead to more problems than obese individuals, as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD. If the precise characteristics of these populations, especially the lean subgroup, are identified, the clinicians would be able to provide more appropriate advice and treatment to these populations. AIM:To investigate the prevalence, clinical characteristics, risk factors, and possible indicators for NAFLD in lean Chinese adults with a normal WC. METHODS:People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included. Their fatty liver index (FLI), abdominal ultrasonography results, and controlled attenuation parameter were all assessed. Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls. RESULTS:A total of 2715 subjects who underwent routine health examinations were included in the study. Among 810 lean participants with a normal WC, 142 (17.5%) fulfilled the diagnostic criteria for NAFLD. Waist-height ratio, hemoglobin, platelets, and triglycerides were significant factors associated with the presence of NAFLD in these participants. The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15, which had a 77.8% sensitivity and 75.9% specificity. There was no significant difference in the single-nucleotide polymorphisms in the , , , , and genes between lean subjects with and without NAFLD ( < 0.05). CONCLUSION:NAFLD is not uncommon in lean Chinese adults even with a normal WC. Metabolic factors, rather than genetic factors, may play important roles in the development of NAFLD in this population. A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC. 10.3748/wjg.v26.i15.1792
    Comparison of thyroid function in different emotional states of drug-naïve patients with bipolar disorder. Zhao Shengnan,Zhang Xu,Zhou Yaling,Xu Hao,Li Yuwei,Chen Yuexin,Zhang Bo,Sun Xueli BMC endocrine disorders BACKGROUND:Previous studies have shown that bipolar disorder is closely related to thyroid dysfunction. Psychiatric drugs have a large or small effect on thyroid function, and thyroid hormone levels can also affect the effect of drug treatment. Therefore, the purpose of this study is assessment the thyroid function of drug-naive bipolar disorder across different mood states, with the expectation of providing support for treatment options. METHODS:The present study is a cross-sectional study. Patients diagnosed with bipolar disorder according to the International Classification of Diseases diagnostic Criteria, Edition 10 (ICD 10) and who had never received medication were included in the study. The Montgomery Depression Scale (MADRS) was used to assess depressive symptoms and the Young Mania Rating Scale (YMRS) for manic symptoms. Thyroid function indicators include thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), and total thyroxine (TT4). Levels of TSH, TT4, FT4, TT3, and FT3 were measured within 48 h of hospitalization, between 06:00 and 08:00. RESULTS:The data analysis finally covered the data of 291 subjects (136 in a bipolar manic group, 128 in a bipolar depressive group, and 27 in a bipolar mixed group), including 140 males and 151 females, with an average age of 27.38 ± 8.01. There was no significant difference in age, sex, marital status, work status, family history, and course of illness among the manic group, depressive group, and mixed group. The level of FT3, the rate of thyroid hormone increased secretion, and the total abnormality rate of thyroid hormone secretion in the manic group were significantly higher than those in the depressive group. CONCLUSION:These findings indicate that thyroid functions were significantly different between depressive and manic episodes in BD patients. In clinical practice, it is necessary to take into account the differences in thyroid hormone levels in patients with BD across different emotional states in choosing drug. 10.1186/s12902-021-00869-5
    Prospectively ascertained mania and hypomania among young adults with child- and adolescent-onset bipolar disorder. Bipolar disorders OBJECTIVES:While adults with bipolar disorder (BD) often report symptoms starting in childhood, continuity of mania and/or hypomania (mania/hypomania) from childhood to adulthood has been questioned. Using longitudinal data from the Course and Outcome of Bipolar Youth (COBY) study, we assessed threshold mania/hypomania in young adults who manifested BD as youth. METHODS:COBY is a naturalistic, longitudinal study of 446 youth with BD (84% recruited from outpatient clinics), 7-17 years old at intake, and over 11 years of follow-up. Focusing on youth with BD-I/II (n = 297), we examined adult mania/hypomania risk (>18 years old; mean 7.9 years of follow-up) according to child (<13 years old) versus adolescent (13-17 years old) onset. We next used penalized regression to test demographic and clinical predictors of young adult mania/hypomania. RESULTS:Most participants (64%) had child-onset mania/hypomania, 57% of whom also experienced mania/hypomania in adolescence. Among those who experienced an episode in adolescence, over 40% also had mania/hypomania during adulthood; the risk did not differ according to child versus adolescent onset. In contrast, 7% with mania/hypomania in childhood, but not adolescence, experienced mania/hypomania in adulthood. Family history (of mania and suicide attempts) predicted mania/hypomania in young adulthood (p-values <0.05); age of onset was not a significant predictor. Among participants with no mania/hypomania during adulthood, 53% (105/198) still experienced subthreshold manic episodes. DISCUSSION:We find substantial continuity across developmental stage indicating that, in this carefully characterized sample, children who experience mania/hypomania-particularly those who also experience mania/hypomania in adolescence-are likely to experience mania/hypomania in young adulthood. 10.1111/bdi.13034
    Gray matter voxel-based morphometry in mania and remission states of children with bipolar disorder. Xiao Qian,Zhong Yuan,Jiao Qing,Lu Guangming,Su Yi Journal of affective disorders BACKGROUND:It has been found by many studies that gray matter (GM) abnormalities exist in both adults and children with bipolar disorder (PBD) which is a serious mental illness characterized by alternating episodes of mania and depression. However, there are few studies on the comparison between brain imaging of different mood states shown by patients with bipolar disorder. This study is aimed at exploring the differences existing in brain structures between children with bipolar disorder and that of healthy controls, and then it tries to further explore whether there is a structural difference between the states of mania and remission in children with bipolar disorder. METHODS:21 PBD-mania subjects, 19 PBD-remission subjects and 18 control subjects aged 12-17 years old were engaged in this study. In the present study, magnetic resonance imaging was obtained by employing a Siemens 3.0 T scanner. With regard to the volumes of gray matter in the mania group, remission group and healthy control group, analysis was carried out by using voxel-based morphometry (VBM). Further analysis was conducted on the correlation between MRI data and clinical features of patients with PBD. RESULTS:In comparison with the healthy control subjects, the gray matter volume measured from the left hippocampus, parahippocampal gyrus and amygdala in both manic and euthymic groups showed a decreasing trend, while the volume of left orbitofrontal cortex increased. However, no significant difference in volumes was found between BD manic and euthymic groups. It was observed that the volume of orbitofrontal cortex had a positive correlation with onset age in PBD euthymic group. CONCLUSIONS:Our study came to the conclusion that extensive brain structural changes are available in patients with PBD. The brain regions with structural changes are distributed in the anterior limbic network (ALN), which has been proved to have been involved in the abnormal emotional and cognitive regulation of PBD. However, there is no difference in the volumes of gray matter between mania and remission in PBD . 10.1016/j.jad.2020.02.042
    Connectomic signatures of working memory deficits in depression, mania, and euthymic states of bipolar disorder. Yang Jie,Ouyang Xuan,Tao Haojuan,Pu Weidan,Fan Zebin,Zeng Can,Huang Xiaojun,Chen Xudong,Liu Jun,Liu Zhening,Palaniyappan Lena Journal of affective disorders BACKGROUND:Working memory (WM) deficit is a feature persistently reported across mania, depression, and euthymic periods of bipolar disorder (BD). WM capacity relates to distributed brain regions that are systemically organized at the connectome level. It is not clear whether the same disruption of this network-level organization underlies the WM impairment seen in different phases of BD. METHODS:We used graph theory to examine the topology of the functional connectome in different granularity in 143 subjects (72 with BD [32 depression; 15 mania; 25 euthymic] and 71 healthy controls) during a n-back task. Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. RESULTS:Altered topological properties characterised by an increase in small-worldness of the whole-brain connectome, were specific for bipolar depressed, but not in manic and euthymic states. Depressed subjects showed a shift in the distribution of the number of connections per brain region (degree) within the connectome during WM task. Increased small-worldness related to worse WM accuracy in patients with more severe depression, anxiety and illness burden. LIMITATIONS:We used only 2-back load, limiting our ability to study the parametric effects of task demand. CONCLUSIONS:We demonstrate a putative state-dependent mechanistic link between connectome topology, hub re-distribution and impaired n-back performance in bipolar disorder. The aberrant task-dependent modulation of the connectome relates to worse WM performance especially when anxiety and depression are prominent in BD. 10.1016/j.jad.2020.05.058
    Cannabis use: A co-existing condition in first-episode bipolar mania patients. Etyemez Semra,Currie Terrence T,Hamilton Jane E,Weaver Michael F,Findley J Chase,Soares Jair,Selek Salih Journal of affective disorders BACKGROUND:An association between first-episode presentation of bipolar mania and concurrent cannabis use disorder has been well established in the current literature (Bally et al., 2014, Baethge et al., 2008). Previous studies have shown that 30-70% of patients admitted for a first manic episode had concurrent cannabis use (Bally et al., 2014). The exact mechanism of this association has yet to be confirmed. AIMS:We aim to evaluate the prevalence of cannabis use in patients with bipolar disorder (BD) admitted to UTHealth Harris County Psychiatric Center (HCPC) for a first manic episode. METHODS:In this retrospective cohort study, 15,969 inpatient records of patients admitted to HCPC between 2012-2013 were examined to identify patients admitted with a first manic episode according to ICD-9 criteria (single episode mania). The prevalence of multiple sociodemographic and clinical variables including cannabis positivity in urine drug screening (UDS) were examined. RESULTS:Twenty patients were admitted for a first manic episode. Half of the patients were females; mean age was 28.65 ± 10.56 years and mean length of stay (LOS) was 7.15 ± 3.72 days. Fifteen patients received a UDS. Of these fifteen, seven were positive for cannabinoids (47%). One patient was positive for phencyclidine (in addition to cannabis) and one patient was positive for amphetamine (but not cannabis). CONCLUSIONS:The prevalence of cannabis use was higher in first-episode mania patients compared to the general population. The influence of cannabis on the first episode of mania requires additional study. 10.1016/j.jad.2019.11.097
    Abnormal Large-Scale Network Activation Present in Bipolar Mania and Bipolar Depression Under Resting State. Zeng Can,Ross Brendan,Xue Zhimin,Huang Xiaojun,Wu Guowei,Liu Zhening,Tao Haojuan,Pu Weidan Frontiers in psychiatry Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA). Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables. Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further -tests showed a gradient descent of activity-depression > HC > mania-in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores. Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top-down regulation in task-independent networks. 10.3389/fpsyt.2021.634299
    Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials. Molecular psychiatry A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo. 10.1038/s41380-021-01334-4
    Cortical source localization during facial emotion recognition in bipolar mania: An ERP study. Sinha Sudip Kumar,Das Basudeb,Munda Sanjay Kumar,Umesh Shreekantiah,Goyal Nishant Asian journal of psychiatry Facial emotion recognition has enormous value for humans in social cognition and thereby day to day functioning. Disturbances in the processing of emotional cues are seen in all the three phases of bipolar disorder and have been proposed as an etiology in the development of bipolar disorder. 30 consented patients with bipolar mania with psychotic symptoms and 30 age and sex matched healthy controls were taken for the study. Facial emotion ecognition task containing four basic emotions namely happy, sad, anger and fear were used. Sixty four (64) channel ERP recordings were done for all the subjects. Source localization was done using sLORETA selecting the window for late positive potentials (LPP). Statistically significant and reduced cortical sources were noted in the right insula (p = 0.004) at the peak of LPP during response to anger facial emotions in bipolar mania patients. Hypoactivation of right insular cortex during response to anger emotion may be due to the aberrant activation and possible failure of interoceptive prediction system during acute manic phase are discussed. 10.1016/j.ajp.2020.102170
    Time to rehospitalization in patients with bipolar mania discharged on long-acting injectable or oral antipsychotics. Lin Ching-Hua,Chan Hung-Yu,Hsu Chun-Chi,Chen Feng-Chua Journal of affective disorders OBJECTIVE:This study aimed to analyze time to rehospitalization in patients with bipolar mania discharged on long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs). Additionally, temporal trends in LAI prescription were investigated. METHODS:Patients with bipolar mania discharged from the study hospital on antipsychotics between 2006 and 2018 were included. Survival analysis was used to compare time to rehospitalization within one year of discharge between patients discharged on LAIs and OAPs, and between FGA-LAIs (first- generation antipsychotic) and SGA-LAIs (second-generation antipsychotic). The Cochrane-Armitage trend test was used to test whether a temporal trend existed for LAI prescription rates during the study period. RESULTS:The LAI group (n = 224) had a significantly lower rehospitalization rate and a significantly longer time to rehospitalization than the OAP group (n = 3836). Rehospitalization rate and time to rehospitalization were not significantly different between patients discharged on FGA-LAIs or SGA-LAIs. The LAI prescription rate grew significantly from 2.20% in 2006 to 11.58% in 2018 (Z = 5.5843, p < 0.0001). The prescription rate of SGA-LAIs also increased significantly (Z = 7.7141, p < 0.0001), but not the prescription rate of FGA-LAIs. LIMITATIONS:The treatment allocation is not randomized in this retrospective study. Furthermore, various clinical characteristics were unavailable in our analysis, such as symptom severity, functional impairment, and others. CONCLUSIONS:LAIs were significantly superior to OAPs in reducing rehospitalization risk. However, SGA-LAIs were comparable with FGA-LAIs in reducing rehospitalization risk. Use of LAIs increased significantly in discharged patients with bipolar disorder during the study period, especially SGA-LAIs. 10.1016/j.jad.2020.10.023
    Opposing Changes in the Functional Architecture of Large-Scale Networks in Bipolar Mania and Depression. Russo Daniel,Martino Matteo,Magioncalda Paola,Inglese Matilde,Amore Mario,Northoff Georg Schizophrenia bulletin OBJECTIVE:Manic and depressive phases of bipolar disorder (BD) show opposite symptoms in psychomotor, thought, and affective dimensions. Neuronally, these may depend on distinct patterns of alterations in the functional architecture of brain intrinsic activity. Therefore, the study aimed to characterize the spatial and temporal changes of resting-state activity in mania and depression, by investigating the regional homogeneity (ReHo) and degree of centrality (DC), in different frequency bands. METHODS:Using resting-state functional magnetic resonance imaging (fMRI), voxel-wise ReHo and DC were calculated-in the standard frequency band (SFB: 0.01-0.10 Hz), as well as in Slow5 (0.01-0.027 Hz) and Slow4 (0.027-0.073 Hz)-and compared between manic (n = 36), depressed (n = 43), euthymic (n = 29) patients, and healthy controls (n = 112). Finally, clinical correlations were investigated. RESULTS:Mania was mainly characterized by decreased ReHo and DC in Slow4 in the medial prefrontal cortex (as part of the default-mode network [DMN]), which in turn correlated with manic symptomatology. Conversely, depression was mainly characterized by decreased ReHo in SFB in the primary sensory-motor cortex (as part of the sensorimotor network [SMN]), which in turn correlated with depressive symptomatology. CONCLUSIONS:Our data show a functional reconfiguration of the spatiotemporal structure of intrinsic brain activity to occur in BD. Mania might be characterized by a predominance of sensorimotor over associative networks, possibly driven by a deficit of the DMN (reflecting in internal thought deficit). Conversely, depression might be characterized by a predominance of associative over sensorimotor networks, possibly driven by a deficit of the SMN (reflecting in psychomotor inhibition). 10.1093/schbul/sbaa004
    Sex difference in the association of body mass index and BDNF levels in Chinese patients with chronic schizophrenia. Yang Fang,Wang Keming,Du Xiangdong,Deng Huiqiong,Wu Hanjing Emily,Yin Guangzhong,Ning Yuping,Huang Xingbing,Teixeira Antonio L,de Quevedo João,Soares Jair C,Li Xiaosi,Lang XiaoE,Zhang Xiang Yang Psychopharmacology RATIONALE AND OBJECTIVE:Schizophrenia displays sex differences in many aspects. Decreased brain-derived neurotrophic factor (BDNF) levels have been reported to be associated with high body weight or obesity as well as other psychopathological aspects in schizophrenia patients. This study aimed to explore sex differences in the relationship between serum BDNF levels and obesity in patients with chronic schizophrenia. METHODS:We recruited 132 Chinese patients with chronic schizophrenia (98 males and 34 females) and compared sex differences in the body mass index (BMI), obesity, serum BDNF levels, and their associations. Psychopathology symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). A regression model with various demographic and clinical variables was applied to predict the serum levels of BDNF. RESULTS:Female patients had a higher rate of obesity and higher BMI, but lower BDNF levels than male schizophrenia patients. A significantly negative correlation was observed between BMI and BDNF levels only in female patients but not in male patients. The multiple regression model with demographic and clinical variables significantly predicted BDNF levels only in female patients, with a medium size effect. And only in female patients, BMI made a significant contribution to this prediction. CONCLUSION:Our results indicate significant sex differences in the obesity, BMI, BDNF levels, and their association in chronic patients with schizophrenia, showing a significant inverse correlation between BMI and BDNF levels only in female patients. Thus, sex needs to be considered when assessing the relationship between BDNF and metabolic syndromes in schizophrenia. 10.1007/s00213-018-5107-1
    Clinical course predicts long-term outcomes in bipolar disorder. Uher Rudolf,Pallaskorpi Sanna,Suominen Kirsi,Mantere Outi,Pavlova Barbara,Isometsä Erkki Psychological medicine BACKGROUND:The long-term outcomes of bipolar disorder range from lasting remission to chronic course or frequent recurrences requiring admissions. The distinction between bipolar I and II disorders has limited utility in outcome prediction. It is unclear to what extent the clinical course of bipolar disorder predicts long-term outcomes. METHODS:A representative sample of 191 individuals diagnosed with bipolar I or II disorder was recruited and followed for up to 5 years using a life-chart method. We previously described the clinical course over the first 18 months with dimensional course characteristics and latent classes. Now we test if these course characteristics predict long-term outcomes, including time ill (time with any mood symptoms) and hospital admissions over a second non-overlapping follow-up period in 111 individuals with available data from both 18 months and 5 years follow-ups. RESULTS:Dimensional course characteristics from the first 18 months prospectively predicted outcomes over the following 3.5 years. The proportion of time depressed, the severity of depressive symptoms and the proportion of time manic predicted more time ill. The proportion of time manic, the severity of manic symptoms and depression-to-mania switching predicted a greater likelihood of hospital admissions. All predictions remained significant after controlling for age, sex and bipolar I v. II disorder. CONCLUSIONS:Differential associations with long-term outcomes suggest that course characteristics may facilitate care planning with greater predictive validity than established types of bipolar disorders. A clinical course dominated by depressive symptoms predicts a greater proportion of time ill. A clinical course characterized by manic episodes predicts hospital admissions. 10.1017/S0033291718001678
    Differences in Demographic and Clinical Characteristics of Patients With Depressive vs. Manic First Episode of Bipolar Disorder. Wang Zhonggang,Cao Yuying,Zhu Yaya,Li Kunkun,Jiang Xianfei,Zhuo Chuanjun,Triplett Patrick,Li Jie Frontiers in psychiatry Bipolar disorder is a serious mental disease marked by episodes of depression, mania, hypomania, or mixed states. Patients with bipolar disorder may present with different symptoms at first onset. The aim of this study is to compare demographic and clinical variables based on a patient's first episode of bipolar disorder, including risk of recurrence over a 2-year period. A large cohort ( = 742) of patients with bipolar disorder in China was analyzed. Patients were divided into two groups according to their first episode of bipolar disorder, either depression or mania. Patients in mixed state first episode were classified based on predominant symptoms. Three hundred eighteen patients of the cohort had a first episode of mania and 424 patients had initial symptoms of depression. Demographic and clinical data were collected. All patients were followed up for 24 months. Data on compliance with follow-up appointments and recurrence of symptoms after 6, 12, 18, and 24 months were collected. Clinical characteristics (course of disease, age of onset, psychiatric family history, etc.) were compared between the mania group and depression groups. More patients with bipolar disorder had a first episode of depression than mania (57.14 vs. 42.86%). Compared with the depression group, the mania group had later age of diagnosis of bipolar disorder [(38.64 ± 13.50) vs. (36.34 ± 14.94), = 0.028], lower education level [(9.37 ± 4.34) vs. (10.17 ± 4.81), = 0.017] and longer latency between an initial episode of psychiatric symptoms and formal bipolar diagnosis [(10.80 ± 10.76) vs. (8.85 ± 9.90), = 0.012]. More patients in the mania group were male and without psychotic symptoms (all < 0.05). In comparison with the mania group, more patients in the depression group were female, with higher frequency of a reported precipitating event before first mood episode (all < 0.05). Compared with the depression group, the mania group had more recurrences of illness at the end of 12 months ( =-2.156, = 0.031), 18 months ( =-2.192, = 0.028), and 24 months ( = -2.364, = 0.018). In our study, there are a number of differences in demographic and clinical characteristics of patients with different onset syndromes of bipolar disorder. These differences include gender, education level, diagnosis age, the rate of recurrences, and others. These data of a cohort of Chinese patients add to the growing international literature on the relationship between index episode of bipolar disorder and clinical variables and outcomes. These results and further study may allow clinicians to offer patients and families more reliable prognostic information at the onset of disease. 10.3389/fpsyt.2021.616415
    Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder. Köhler-Forsberg Ole,Sylvia Louisa,Deckersbach Thilo,Ostacher Michael Joshua,McInnis Melvin,Iosifescu Dan,Bowden Charles,McElroy Susan,Calabrese Joseph,Thase Michael,Shelton Richard Charles,Tohen Mauricio,Kocsis James,Friedman Edward,Ketter Terence,Nierenberg Andrew Alan Acta neuropsychiatrica OBJECTIVE:Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. METHODS:We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. RESULTS:The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32-1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=-0.19-1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. CONCLUSION:Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings. 10.1017/neu.2017.34
    Gender differences in characteristics and outcomes of smokers diagnosed with psychosis participating in a smoking cessation intervention. Filia Sacha L,Baker Amanda L,Gurvich Caroline T,Richmond Robyn,Lewin Terry J,Kulkarni Jayashri Psychiatry research While research has identified gender differences in characteristics and outcomes of smokers in the general population, no studies have examined this among smokers with psychosis. This study aimed to explore gender differences among 298 smokers with psychosis (schizophrenia, schizoaffective and bipolar affective disorder) participating in a smoking intervention study. Results revealed a general lack of gender differences on a range of variables for smokers with psychosis including reasons for smoking/quitting, readiness and motivation to quit, use of nicotine replacement therapy, and smoking outcomes including point prevalence or continuous abstinence, and there were no significant predictors of smoking reduction status according to gender at any of the follow-up time-points. The current study did find that female smokers with psychosis were significantly more likely than males to report that they smoked to prevent weight gain. Furthermore, the females reported significantly more reasons for quitting smoking and were more likely to be driven by extrinsic motivators to quit such as immediate reinforcement and social influence, compared to the male smokers with psychosis. Clinical implications include specifically focussing on weight issues and enhancing intrinsic motivation to quit smoking for female smokers with psychosis; and strengthening reasons for quitting among males with psychosis. 10.1016/j.psychres.2014.01.002
    Screening for bipolar disorder: does gender distort scores and case-finding estimates? Parker Gordon,Fletcher Kathryn,McCraw Stacey,Synnott Howe,Friend Paul,Mitchell Philip B,Hadzi-Pavlovic Dusan Journal of affective disorders BACKGROUND:Gender differences in rates of bipolar disorder have been described, with most studies reporting males as over-represented in those diagnosed with a bipolar I disorder and females over-represented in those diagnosed with a bipolar II disorder. This could reflect true differences in prevalence or measurement error emerging from screening or case-finding measures. We examine the possible contribution of the latter by examining one screening measure-the Mood Swings Questionnaire (MSQ). METHODS:We analyse MSQ data from a large sample of age- and gender-matched bipolar I and bipolar II patients (and their composite group). Gender differences were examined in terms of prevalence and severity of MSQ symptoms, MSQ sub-scales scores and total MSQ scores, employing univariate and differential item functioning (DIF) analyses. RESULTS:Both male and female bipolar I patients reported higher total MSQ and higher mysticism MSQ sub-scale scores than their male and female bipolar II counterparts. There were no gender differences when bipolar I, bipolar II and composite bipolar groups were separately examined on both total and sub-scale MSQ scores, suggesting that gender does not impact on MSQ scoring. When item analyses of bipolar I and II groups were undertaken separately, a number of differences emerged, but as few were consistent across bipolar sub-types such differences could reflect chance and failure to control for multiple comparisons. The over-representation of some items in females and some in males may have contributed to the comparable total and sub-scale scores. LIMITATIONS:Large sample size and only one measure (i.e. MSQ) examined. CONCLUSION:As total and sub-scale MSQ scores were uninfluenced by gender we can conclude that this screening test is not confounded by gender and, if representative of other such screening measures, would indicate that any differential prevalence of the bipolar disorders identified in community studies possibly reflects gender differences in their occurrence rather than artefactual consequences of screening measures having a gender bias. 10.1016/j.jad.2014.03.032
    The relationship between inflammatory state and quantity of affective episodes in bipolar disorder. Queissner Robert,Pilz René,Dalkner Nina,Birner Armin,Bengesser Susanne A,Platzer Martina,Fellendorf Frederike T,Kainzbauer Nora,Herzog-Eberhard Simone,Hamm Carlo,Reininghaus Bernd,Zelzer Sieglinde,Mangge Harald,Mansur Rodrigo B,McIntyre Roger S,Kapfhammer Hans-Peter,Reininghaus Eva Z Psychoneuroendocrinology OBJECTIVES:Immunological/inflammatory processes have been proposed to play an important role in the pathophysiology of mood disorders, including bipolar disorder (BD). The present study aimed to examine the influence of immune activation, measured on the basis of inflammatory markers, on the course of illness, proxied by the number of affective episodes, in patients with BD. METHODS:We investigated the relationship between high-sensitive CRP (hsCRP) and Interleukin 6 (IL-6), two inflammatory markers and characteristics of course of illness (e.g. number of affective episodes, depressive and manic symptoms) amongst a group of 190 individuals with BD. RESULTS:Among females with BD, there was a positive correlation between levels of hsCRP and the number of manic and depressive episodes. Moreover, levels of hsCRP and IL-6 were positively correlated with current manic symptoms, as measured by Young-Mania-Rating-Scale. There were no significant correlations between levels of the foregoing inflammatory markers, and manic and depressive symptoms in male individuals with BD. Furthermore, compared to their untreated counterparts, female patients treated with lithium demonstrated higher levels of hsCRP and male patients treated with atypical antipsychotics lower levels of hsCRP, respectively. CONCLUSIONS:Our results are suggesting that the association between inflammatory state and affective response in patients with BD may be gender-dependent. A future research would be to evaluate whether or not these gender differences can be observed in other inflammatory pathways associated with BD. 10.1016/j.psyneuen.2018.01.024
    Influence of gender on inpatient treatment for bipolar disorder: An analysis of 60,607 hospitalisations. Fellinger Matthäus,Waldhör Thomas,Blüml Victor,Williams Nolan,Vyssoki Benjamin Journal of affective disorders BACKGROUND:The influence of gender on inpatient treatment patterns in bipolar patients is unclear. The aim of this study is to examine whether differences in length of stay and frequency of inpatient episodes, according to ICD-10 bipolar disorder (BD)-subgroups, exist between men and women. METHODS:All episodes of a manic (F31.0-2), depressive (F31.3-5) or mixed (F31.6) subtype of BD during an inpatient stay in an Austrian hospital in the period of 2001-2014 were included in this study. Data on episodes was provided by the national statistics agency. Weekly admission rates per 100,000 people were calculated by directly age-standardized rates. RESULTS:The database comprised 60,607 admissions (35.8% men). The number of inpatient episodes was significantly higher (p < 0.001) in women in all BD subgroups. Average length of stay in manic (p < 0.001) and depressive (p < 0.001) episodes was shorter in women compared to men. No difference could be found for mixed episodes. LIMITATIONS:Only aggregated patient data and no single case histories were available for this study. CONCLUSIONS:The current study reveals relevant gender differences regarding inpatient treatment patterns, as women were overrepresented in all BD-subgroups. Despite equal life time prevalence, severe mood episodes lead more often to hospitalisations in women. There is a high necessity to further research the underlying causes of these findings. 10.1016/j.jad.2017.08.007
    Risks associated with gender differences in bipolar I disorder. Azorin Jean-Michel,Belzeaux Raoul,Kaladjian Arthur,Adida Marc,Hantouche Elie,Lancrenon Sylvie,Fakra Eric Journal of affective disorders BACKGROUND:Previous studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial. METHODS:The demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender. RESULTS:Bipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (-), excessive alcohol use (+), cyclothymic temperament (-), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+). LIMITATIONS:The retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations. CONCLUSIONS:Findings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients. 10.1016/j.jad.2013.08.031
    Gender influence on the bipolar disorder inpatient length of stay in Sweden, 2005-2014: A register-based study. Ragazan Dragos C,Eberhard Jonas,Ösby Urban,Berge Jonas Journal of affective disorders BACKGROUND:The influence of gender on bipolar disorder is controversial and it is unclear if inpatient care differs between men and women. Here, we investigate for gender differences in the inpatient length of stay for Swedes admitted for bipolar disorder and explore other factors that could explain any observed association. METHODS:Admission data were extracted from the Swedish National Patient Register and included all patients first admitted to a psychiatric inpatient unit with a bipolar disorder diagnosis, circa 2005-2014. Patients were then retrospectively followed for subsequent hospitalizations. Diagnostic subtypes were categorized by ICD-10 clusters: depressive, depressive with psychotic features, manic, manic with psychotic features, mixed, and other. Psychotropic therapies preceding the corresponding admissions were attained from the Prescribed Drug Register. Mixed-effects zero-truncated negative binomial regressions were employed to model the length of stay per admission. RESULTS:Analysis included 39,653 admissions by 16,271 inpatients (60.0% women). Overall, when compared to men, women spent 7.5% (95% CI: 4.2-11.0%, p < 0.001) extra days hospitalized per admission. However, upon adjusting for candidate confounders, including the bipolar subtype, and selected comorbidities and psychotropics, the association weakened wherein women then spent 3.7% (95% CI: 0.1-6.9%, p = 0.028) extra days hospitalized per admission. LIMITATIONS:The integrity of register data can be variable and the adherence to outpatient dispensed psychotropics could not be validated. CONCLUSION:Although the influence of gender on the bipolar disorder inpatient length of stay is evident, other factors attenuate and better explain this crude observation. 10.1016/j.jad.2019.05.052
    Sex difference in glia gene expression in the dorsolateral prefrontal cortex in bipolar disorder: Relation to psychotic features. Zhang Lin,Verwer Ronald W H,Lucassen Paul J,Huitinga Inge,Swaab Dick F Journal of psychiatric research BACKGROUND:Suicide, psychotic features and gender influence the epidemiology and clinical prognosis of bipolar disorder (BD). Differences in glial function between the genders might contribute to these clinical variables. Here we studied expression of glial genes in human post-mortem prefrontal cortex of BD and control subjects in relation to suicide, psychotic features and sex. METHODS:Real time PCR was used to detect transcriptional alterations of 16 glia-related genes in two brain areas, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), from 30 patients with BD subdivided by suicide and psychotic features, and from 34 well-matched control cases. RESULTS:We found no evidence of immune activation in BD. Instead, we found three microglial genes to be downregulated in the DLPFC of non-suicidal individuals with BD, i.e. CD68, triggering receptor expressed on myeloid cells 2 (TREM2) and purinergic receptor 12 (P2RY12). A remarkable sex difference was observed in the DLPFC of patients with BD: 14 glia-related genes were expressed at significantly higher levels in males, including all three glial cell types. A subset analysis showed that the sex differences were closely associated with the presence of psychotic features. CONCLUSIONS:No evidence of immune activation was found in these two brain regions in BD. The sex-specific differences in glial gene expression in BD, found particularly in patients with psychotic features, may be associated with the potential co-existence of mania and psychotic features and could potentially contribute to the gender-biased characteristics in BD. 10.1016/j.jpsychires.2020.03.003
    Gender Differences and Comorbidities in U.S. Adults with Bipolar Disorder. Patel Rikinkumar S,Virani Sanya,Saeed Hina,Nimmagadda Sai,Talukdar Jupi,Youssef Nagy A Brain sciences BACKGROUND:Past studies have evaluated the association of various comorbidities with bipolar disorder. This study analyzes differences in the prevalence and association of medical and psychiatric comorbidities in bipolar patients by gender. METHODS:A retrospective analysis was conducted using the Nationwide Inpatient Sample (2010⁻2014). Using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, we narrowed the study population to comprise those with a primary diagnosis of bipolar disorder and then obtained information about comorbidities. The differences in comorbidities by gender were quantified using chi-square tests and the logistic regression model (odds ratio (OR)). RESULTS:Hypertension (20.5%), asthma (12.5%) and hypothyroidism (8.1%) were the top medical comorbidities found in bipolar patients. Migraine and hypothyroidism were seen three times higher in females (OR = 3.074 and OR = 3.001; respectively). Females with bipolar disorder had higher odds of comorbid inflammatory disorders like asthma (OR = 1.755), Crohn's disease (OR = 1.197) and multiple sclerosis (OR = 2.440) compared to males. Females had a two-fold higher likelihood of comorbid post-traumatic stress disorder (PTSD) (OR = 2.253) followed by personality disorders (OR = 1.692) and anxiety disorders (OR = 1.663) compared to males. CONCLUSION:Women with bipolar disorder have a much higher medical comorbidity burden than men and may highly benefit from an integrated team of physicians to manage their condition and improve their health-related quality of life. 10.3390/brainsci8090168
    Gender differences in thyroid system function: relevance to bipolar disorder and its treatment. Bauer Michael,Glenn Tasha,Pilhatsch Maximilian,Pfennig Andrea,Whybrow Peter C Bipolar disorders OBJECTIVES:Thyroid hormones play a critical role in the functioning of the adult brain, and thyroid diseases impair both mood and cognition. This paper reviews gender differences in thyroid system function that are relevant to the diagnosis and treatment of bipolar disorder. METHODS:The study comprised a comprehensive literature review of gender differences in thyroid disease that are pertinent to mood disorders. RESULTS:The prevalence of thyroid disease was found to be much higher in females than males, and to increase with age. The most commonly detected abnormality was subclinical hypothyroidism, which was found to occur in up to 20% of postmenopausal women. Females also had higher rates of thyroid autoimmunity. Individuals at risk for thyroid disease, such as adult females, may have had less ability to compensate for additional challenges to thyroid metabolism, including lithium treatment. Thyroid abnormalities were associated with a poorer response to standard treatments for mood disorders. Females with treatment-resistant mood disorders may have responded better than males to adjunctive therapy with thyroid hormones. CONCLUSIONS:Disturbances of thyroid system function, which occur commonly in females, may complicate the diagnosis and treatment of mood disorders. In particular, this is clinically relevant during lithium treatment because lithium may impair vital thyroid metabolic pathways secondary to its anti-thyroid activity. 10.1111/bdi.12150
    Gender differences of amplitude of low-frequency fluctuations in bipolar disorder: A resting state fMRI study. Jiang Xuejun,Wu Feng,Zhang Yifan,Li Huizi,Kang Jiahui,Kong Lingtao,Wang Fei,Tang Yanqing Journal of affective disorders BACKGROUND:The clinical and epidemiological features of bipolar disorder (BD) between females and males have many differences. The association between brain function and gender in BD is unknown. This research aimed to investigate the association between brain function and gender in BD by using amplitude of low-frequency fluctuations (ALFFs). METHODS:Ninety-eight patients (49 females and 49 males) with BD and 171 matched healthy controls (HCs, 89 females and 82 males) were recruited for resting-state functional magnetic resonance imaging. ALFF was used to estimate brain function. RESULTS:A main effect of diagnosis in ALFF was observed in the dorsal lateral prefrontal cortex (DLPFC), ventral prefrontal cortex (VPFC), caudate and occipital lobe. A main effect of gender in ALFF was found in the right VPFC, DLPFC, thalamus, and occipital lobe. A main effect of diagnosis gender interaction in ALFF was observed in the left DLPFC. Analyses of two-sample t-test indicated that male patients with BD had increased ALFF in the right hippocampus, right amygdala, left caudate, and left DLPFC, and decreased ALFF in the occipital lobe compared with male HC. Female patients with BD demonstrated increased ALFF in the right VPFC and right DLPFC compared with female HC. Male patients with BD exhibited increased ALFF in the right VPFC and left DLPFC and decreased ALFF in the occipital lobe compared with female patients with BD. LIMITATIONS:This study did not consider the effect of medications and emotional states on brain activity. CONCLUSIONS:Results suggested gender differences in the dysfunctions of the cortico-limbic neural system in BD. 10.1016/j.jad.2020.11.087
    Sex differences in the association between nonalcoholic fatty liver disease and Parkinson's disease. Jeong Su-Min,Lee Han Rim,Jang Wooyoung,Kim Dahye,Yoo Jung Eun,Jeon Keun Hye,Jin Sang-Man,Han Kyungdo,Shin Dong Wook Parkinsonism & related disorders BACKGROUND:The association between nonalcoholic fatty liver disease (NAFLD) and Parkinson's disease (PD) remains uncertain. This study sought to assess the sex-specific association between NAFLD and PD risk considering that sex is an important factor in both conditions. METHODS:We included 2,651,169 men and 2,998,904 women (≥40 years of age) who underwent health examinations in 2009 using database of the Korean National Health Insurance Service. To define NAFLD, the Fatty Liver Index (FLI) was used and a score of at least 60 points was regarded as suggesting the presence of NAFLD. Cox proportional hazards analyses were performed to evaluate the association between the presence of NAFLD/each component of FLI and the risk of PD. All analyses were stratified by sex. RESULTS:The median follow-up duration was 7.3 years in both men and women. Of the total study population, 23,233 patients with PD (10,578 men and 12,655 women) were identified. Among men, a decreased risk of PD was observed in those with NAFLD [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI): 0.82-0.91]. In contrast, among women, an increased risk of PD was observed in those with NAFLD (aHR: 1.09, 95% CI: 1.02-1.16). This different association according to sex was more prominent among younger participants but was not significant in the old age group. CONCLUSIONS:NAFLD defined by FLI is differently associated with the risk of PD by sex (i.e., low risk of PD in men with NAFLD vs. high risk of PD in women with NAFLD). 10.1016/j.parkreldis.2021.10.030
    Sex-related variation of neurocognitive functioning in bipolar disorder: Focus on visual memory and associative learning. Tournikioti Kalliopi,Ferentinos Panagiotis,Michopoulos Ioannis,Dikeos Dimitris,Soldatos Constantin R,Douzenis Athanasios Psychiatry research Bipolar disorder (BD) is associated with cognitive deficits in attention, verbal memory and executive functions. However, only few studies have examined sex effects on cognition despite their clinical relevance. Given that visual memory/ learning has been understudied the aim of our study was to investigate sex-related variation in cognition (executive functions and visual memory/ learning) in BD. Cognitive performance of 60 bipolar-I patients and 30 healthy controls was evaluated by using CANTAB battery tasks targeting spatial memory (SRM), paired associative learning (PAL) and executive functions. We fitted a multivariate analysis of covariance (MANCOVA), followed by task-specific ANCOVAs. A significant diagnosis by sex interaction effect was detected (MANCOVA); specifically, diagnosis-specific sex effects were found for SRM and PAL, as healthy males outperformed healthy females but this pattern was attenuated in BD patients. Patients' clinicodemographic characteristics, current psychopathology or medication status did not differ across sexes and were, therefore, unlikely to explain detected sex effects. Our study is one of few studies to assess sex-related variation in cognition in BD and the first to record a diagnosis-specific sex effect for two tasks of visuo-spatial memory/ learning, indicating that sex-related variation in healthy subjects is disrupted in BD. 10.1016/j.psychres.2018.06.037
    Seasonality in bipolar disorder: Effect of sex and age. Fellinger Matthäus,Waldhoer Thomas,König Daniel,Hinterbuchinger Barbara,Pruckner Nathalie,Baumgartner Josef,Vyssoki Sandra,Vyssoki Benjamin Journal of affective disorders BACKGROUND:Mood episodes in bipolar disorder (BD) are reported to exhibit a seasonal pattern (SP). However, it is unclear whether this pattern is influenced by a patient's sex and age. METHODS:In this nationwide registry study, we examined all inpatient treatments due to a manic (F31.0-2), depressive (F31.3-5) or mixed (F31.6) BD-episode in Austria for 2001-2014. Calculations were based on directly age-standardized rates and seasonality was analyzed on a monthly basis. RESULTS:The database comprised 60,607 admissions (35.8% men). SP were shown for women during manic (summer-autumn), depressive (winter) and mixed (summer) episodes, for men only during manic (summer) episodes. However, no significant sex differences (manic p = 0.101, depressive p = 0.295, mixed p = 0.622 episode) were found. Women at young age (15-35 years) seemed to be more vulnerable to a SP in manic and mixed episodes. LIMITATIONS:Only aggregated patient data of inpatient treatments and no single case histories were available. CONCLUSIONS:In this nationwide registry study, a distinct SP could be shown for manic episodes in men and women, as well as a SP for depressive and mixed episodes in women. As no significant difference in any BD-subgroup could be observed, the effect of sex on the SP seems to be small, if existing at all. However, when taking age into account, we observed a higher likelihood for a SP in young women. Single case studies with information on possible further influencing factors (e.g. medication use) might help to clarify the impact of sex and age on SP in more detail. 10.1016/j.jad.2018.09.073
    Gender and mental health service use in bipolar disorder: national cohort study. Cunningham Ruth,Crowe Marie,Stanley James,Haitana Tracy,Pitama Suzanne,Porter Richard,Baxter Jo,Huria Tania,Mulder Roger,Clark Mau Te Rangimarie,Lacey Cameron BJPsych open BACKGROUND:Despite evidence of gender differences in bipolar disorder characteristics and comorbidity, there is little research on the differences in treatment and service use between men and women with bipolar disorder. AIMS:To use routine data to describe specialist mental health service contact for bipolar disorder, including in-patient, community and support service contacts; to compare clinical characteristics and mental health service use between men and women in contact with secondary services for bipolar disorder. METHOD:Cross-sectional analysis of mental health patients with bipolar disorder in New Zealand, based on complete national routine health data. RESULTS:A total of 3639 individuals were in contact with specialist mental health services with a current diagnosis of bipolar disorder in 2015. Of these 58% were women and 46% were aged 45 and over. The 1-year prevalence rate of bipolar disorder leading to contact with specialist mental health services was 1.56 (95% CI 1.50-1.63) per 100 000 women and 1.20 (95% CI 1.14-1.26) per 100 000 men. Rates of bipolar disorder leading to service contact were 30% higher in women than men (rate ratio 1.30, 95% CI 1.22-1.39). The majority (68%) had a diagnosis of bipolar I disorder. Women were more likely to receive only out-patient treatment and have comorbid anxiety whereas more men had substance use disorder, were convicted for crimes when unwell, received compulsory treatment orders and received in-patient treatment. CONCLUSIONS:Although the prevalence of bipolar disorder is equal between men and women in the population, women were more likely to have contact with specialist services for bipolar disorder but had a lower intensity of service interaction. 10.1192/bjo.2020.117
    Response to lithium and anticonvulsants among patients with bipolar disorder with and without comorbid epilepsy - A nation-wide population-based longitudinal study. Journal of affective disorders OBJECTIVE:In a nation-wide population-based longitudinal register linkage study for the first time 1) to investigate long-term response to lithium in patients with bipolar disorder with and without comorbid epilepsy, and 2) within patients with bipolar disorder and comorbid epilepsy to compare differences in responses between lithium, valproate and lamotrigine. METHODS:We used Danish nation-wide population-based longitudinal register linkage to identify 154 patients with bipolar disorder and comorbid epilepsy and 8381 patients with bipolar disorder without comorbid epilepsy during a study period from 1995 to 2017. Response was defined as continuous monotherapy with lithium, valproate or lamotrigine without switch to or add-on of an antipsychotic drug or an antidepressant or hospitalization during an up to ten-year follow-up period. We calculated standardized absolute risks and differences thereof with respect to age, gender, socioeconomic status and comorbidity with other physical disorders than epilepsy. RESULTS:Response to lithium was decreased in patients with bipolar disorder with versus without comorbid epilepsy during the ten-year follow-up period and the difference remained after standardization for comorbidity with other physical disorders than epilepsy. Within patients with bipolar disorder and comorbid epilepsy, response to lithium was decreased compared with responses to valproate and lamotrigine. CONCLUSIONS:The findings suggest that valproate and lamotrigine should be given priority in patients with comorbid bipolar disorder and epilepsy. The study highlights the need for closely clinical monitoring and psychological support for patients with bipolar disorder and comorbid epilepsy and emphasize the need for further long-term studies of effect of interventions. 10.1016/j.jad.2022.04.098
    Sex differences in the association between serum BDNF and cognitive impairment in schizophrenia patients using various antipsychotics. Dong Rui,Zhao Ning Olivia,Wu Hanjing Emily,Yu Liling,Zhang Xiang Yang Journal of psychiatric research BACKGROUND:Cognitive impairment is one of the core symptoms of schizophrenia patients. There are often various differences in the efficacy of different antipsychotics in the treatment of cognitive impairment by sex. The purpose of this study was to explore whether there are gender differences in the association between serum BDNF levels and cognitive performance in patients with schizophrenia taking different antipsychotics. METHODS:We used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess the cognitive function of three groups of schizophrenia patients (420 on clozapine, 183 on risperidone, 215 on typical antipsychotic drugs) and 467 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia symptoms of patients. Enzyme-Linked ImmunoSorbent Assay was used to measure serum brain-derived neurotrophic factor (BDNF) levels. RESULTS:Among the patients taking clozapine and typical antipsychotic drugs, the RBANS total score, immediate memory, attention, and delayed memory subscores in females were higher than those in males (all p < 0.05). The RBANS total score and the delayed memory subscores in female patients taking risperidone were higher than those in male patients (all p < 0.05). Significant correlation between BDNF and cognition only existed in male patients taking clozapine, male patients taking risperidone, and male and female patients taking typical antipsychotic drugs (all p < 0.05). CONCLUSION:Regardless of antipsychotic effect, the cognitive function of female patients is better compared to that of male patients. For male patients, the association between BDNF and cognitive performance exists in each medication group. For female patients, this significant association was only shown in the typical antipsychotic group, but not in the clozapine and risperidone groups. 10.1016/j.jpsychires.2021.04.026
    Gender differences in C-reactive protein and homocysteine modulation of cognitive performance and real-world functioning in bipolar disorder. Sanchez-Autet M,Arranz B,Safont G,Sierra P,Garcia-Blanco A,de la Fuente L,Garriga M,García-Portilla M P Journal of affective disorders BACKGROUND:Cognitive and psychosocial impairment has been associated with increased levels of C-reactive protein (CRP) and homocysteine in bipolar disorder, but gender differences have seldom been studied. METHODS:Two hundred and twenty-four bipolar outpatients were included. Cognitive performance was assessed through the Screen for Cognitive Impairment in Psychiatry (SCIP). Psychosocial functioning was evaluated using the Functioning Assessment Short Test (FAST) and the General Assessment of Functioning (GAF). Homocysteine and CRP levels were determined. Separate analyses were performed by gender. Partial correlations were calculated to test for associations between biomarkers and cognitive and psychosocial functioning. Hierarchical multiple regression was used to assess factors predicting cognitive and psychosocial functioning. Covariates were: age, education, duration of illness, hospital admissions, depressive symptoms, tobacco consumption, and BMI. RESULTS:A better performance was noted in women in delayed verbal learning (p = 0.010), along with better occupational functioning (p = 0.027) and greater leisure time impairment (p = 0.034). In men, CRP and homocysteine levels were associated with psychosocial dysfunction (interpersonal relationships and financial functioning, respectively). In women, CRP levels correlated with cognitive performance (SCIP total raw score, immediate and delayed verbal learning, and verbal fluency). CRP was a predictor of cognitive performance in women only. LIMITATIONS:The choice of the cognitive scale and covariates and the lack of a control group may be the main limitations. CONCLUSIONS:A gender difference was found in biomarker modulation of cognition and psychosocial functioning. A gender-based approach to cognition and real-world functioning should be considered in bipolar disorder to ensure an optimal outcome. 10.1016/j.jad.2017.12.038
    Sex differences in cognitive function of first-diagnosed and drug-naïve patients with bipolar disorder. Xu Xuelei,Xiang Hui,Qiu Yan,Teng Ziwei,Li Sujuan,Huang Jing,Chen Jindong,Tang Hui,Jin Kun,Jiang Lili,Wang Bolun,Zhao Ziru,Wu Haishan Journal of affective disorders BACKGROUND:Bipolar disorder (BD) is a severe mental illness that affects more than 1% the world's population with high recurrence rates and a series of comorbidities. Cognitive dysfunction is an endophenotype of BD, but sex influences in cognitive impairment remains unclear. METHOD:We evaluated the performance of 139 patients with first-diagnosed, drug-naïve BD (44 males and 95 females) and 92 healthy controls (24 males and 68 females) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale and the Stroop color-word test. RESULT:Immediate memory, visuospatial/constructional ability, language, attention, delayed memory, total RBANS score, and Stroop color-word scores were significantly lower in patients with first-diagnosed, drug-naïve BD than healthy participants. Thus, male patients had worse attention and delayed memory scores compared with female patients with BD. Importantly, a worse performance in visuospatial/constructional ability was negatively associated with the Young Mania Rating Scale score in male patients only. CONCLUSION:Male patients with first-diagnosed, drug-naïve bipolar disorder had worse cognitive dysfunction than female patients in attention and delayed memory. Cognitive deficits were correlated with mania severity only in male patients. These findings reveal the sexual dimorphism in the cognitive deficits of early BD patients with mild and moderated symptoms for further pathophysiological exploration. 10.1016/j.jad.2021.08.125
    Gender differences in socio-demographics, clinical characteristic and quality of life in patients with schizophrenia: A community-based study in Shenzhen. Peng Xiaodong,Wang Shibin,Bi Jianqiang,You Liqin,Zhou Zhijian,Tan Wenyan,Xie Haiyan,Hu Chiyi,Ng Chee H,Liu Tiebang Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists INTRODUCTION:The objective of this study was to explore the gender differences of community-dwelling patients with schizophrenia in terms of socio-demographics, clinical characteristic and quality of life (QOL). METHODS:A total of 433 community-dwelling patients with schizophrenia were recruited in Shenzhen city, China. Data were obtained from a face-to-face interview with standard research questionnaire. The QOL and insight were assessed using the WHOQOL-BREF and the Chinese version of the insight and treatment attitude questionnaire, respectively. RESULTS:This cross-sectional study included 206 male and 227 female patients. Male patients were more likely to be educated, employed, smoking cigarettes and drinking alcohol, and have an early age of illness onset. In contrast, female patients were more likely to be married/cohabitating and have drug side effects. There was no significant difference between genders across all QOL domain. Multiple regression analyzes showed that mental symptoms were negatively associated with all QOL domains, whereas frequency of exercise in the past year was positively associated with all QOL domains. Higher education levels, household per capita annual income in past year (≥100 000 RMB), employment status, IATQ score, drug side effects, marital status, and number of hospitalization were also significantly associated with specific QOL domains. DISCUSSION:There was significant gender difference in socio-demographics and clinical characteristics among community schizophrenia patients in Shenzhen city. Gender-specific intervention measures are needed to improve the functioning and QOL in patients with schizophrenia. 10.1111/appy.12446
    Gender differences in the relationship of childhood trauma and the course of illness in schizophrenia. Kocsis-Bogár Krisztina,Mészáros Veronika,Perczel-Forintos Dóra Comprehensive psychiatry INTRODUCTION:Different types of childhood trauma have been repeatedly shown to contribute to psychotic symptoms. Gender differences in schizophrenia are well known. Some studies argue that trauma history means a significantly higher risk of psychosis for women than men. However, there is evidence of early adverse life events to be associated with higher stress-sensitivity in men. Little is known about the connection of specific type of trauma and specific psychotic symptoms as well as the course of illness with explicit regard to gender differences. METHODS:102 men and women with schizophrenia spectrum disorder were tested using Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Scale for Assessing Positive Symptoms, Early Trauma Inventory-SR. RESULTS:Although, women had a later age at onset without regarding trauma history (d = 0.74), this difference became non-significant when introducing trauma variables. Patients reporting physical abuse had a significantly earlier age at onset, regardless of their sex (V = 0.13, F = 3.11, p = 0.03. Physical abuse predicted an earlier age at onset only in women (R = 0.23). History of general trauma predicted more frequent hospitalizations only in men (R = 0.55). CONCLUSIONS:Although women generally tend to have a more favorable course of illness including a later age at onset men, women with CPA seem to lose this "advantage". It is necessary to investigate the contribution of gender interacting with adverse life events in contribution to the phenomenology and etiology of schizophrenia. 10.1016/j.comppsych.2018.01.007
    Gender differences of neurocognitive functioning in patients with first-episode schizophrenia in China. Pu Chengcheng,Qiu Yujia,Zhou Tianhang,Yang Fude,Lu Zheng,Wang Chuanyue,Deng Hong,Zhao Jingping,Shi Chuan,Yu Xin Comprehensive psychiatry AIMS:To investigate the gender differences in neurocognitive functioning in patients with first-episode schizophrenia (FES) in China. METHODS:A total of 449 Chinese patients with FES (210 males, 239 females) were included in this study. Participants' psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS). Neurocognitive functioning was assessed by 10 neuropsychological tests from a battery. Neurocognitive test scores were converted to scale scores and t-scores using normative data from Chinese populations. RESULTS:Males were younger and less likely to be married, had an earlier age of illness onset and a longer duration of untreated psychosis (DUP), and scored higher on the PANSS negative, general and total scales than females. After controlling for potential confounders, females performed better than males in the verbal learning and memory domain (p=0.016). While most neurocognitive domains were correlated with PANSS negative scores for male patients with FES, for female patients with FES, negative associations were found between scores on the PANSS general subscales and neurocognitive domains. We also performed a case-control comparison with a group of patients with clinically stable schizophrenia (CSS) (n=60) who were matched by age, sex and education years with patients with FES (n=58). After controlling for potential confounders, no significant differences were found between patients with FES and patients with CSS in all neurocognitive domains. Female patients still performed better in the verbal learning and memory domain (t=2.14, p=0.034). No interaction effects of gender and disease were found. CONCLUSIONS:Gender was an independent influence factor for the verbal learning and memory domain. Both female patients with first-episode schizophrenia and female patients with clinically stable schizophrenia performed better than male patients. 10.1016/j.comppsych.2019.152132
    Co-prescription of medication for bipolar disorder and diabetes mellitus: a nationwide population-based study with focus on gender differences. Svendal Gjertrud,Fasmer Ole Bernt,Engeland Anders,Berk Michael,Lund Anders BMC medicine BACKGROUND:Studies have shown a correlation between bipolar disorder and diabetes mellitus. It is unclear if this correlation is a part of common pathophysiological pathways, or if medication for bipolar disorder has negative effects on blood sugar regulation. METHODS:The Norwegian prescription database was analyzed. Prescriptions for lithium, lamotrigine, carbamazepine and valproate were used as proxies for bipolar disorder. Prescriptions for insulin and oral anti-diabetic agents were used as proxies for diabetes mellitus. We explored the association between medication for bipolar disorder and diabetes medication by logistic regression RESULTS:We found a strong association between concomitant use of medication to treat diabetes mellitus and mood stabilizers for the treatment of bipolar disorder. Females had a 30% higher risk compared to men of being treated for both disorders. Persons using oral anti-diabetic agents had higher odds of receiving valproate than either lithium or lamotrigine. Use of insulin as monotherapy seemed to have lower odds than oral anti-diabetic agents of co-prescription of mood stabilizers, compared to the general population. CONCLUSIONS:This study showed a strong association between the use of mood stabilizers and anti-diabetic agents. The association was stronger among women than men. 10.1186/1741-7015-10-148
    Sex differences in schizophrenia, bipolar disorder, and post-traumatic stress disorder: Are gonadal hormones the link? Gogos Andrea,Ney Luke J,Seymour Natasha,Van Rheenen Tamsyn E,Felmingham Kim L British journal of pharmacology In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident in schizophrenia, bipolar disorder, and post-traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men. By contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that oestradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on oestradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders. LINKED ARTICLES: This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc. 10.1111/bph.14584
    Sleep loss as a trigger of mood episodes in bipolar disorder: individual differences based on diagnostic subtype and gender. Lewis Katie Swaden,Gordon-Smith Katherine,Forty Liz,Di Florio Arianna,Craddock Nick,Jones Lisa,Jones Ian The British journal of psychiatry : the journal of mental science Sleep loss may trigger mood episodes in people with bipolar disorder but individual differences could influence vulnerability to this trigger.To determine whether bipolar subtype (bipolar disorder type I (BP-I) or II (BD-II)) and gender were associated with vulnerability to the sleep loss trigger.During a semi-structured interview, 3140 individuals (68% women) with bipolar disorder (66% BD-I) reported whether sleep loss had triggered episodes of high or low mood. DSM-IV diagnosis of bipolar subtype was derived from case notes and interview data.Sleep loss triggering episodes of high mood was associated with female gender (odds ratio (OR) = 1.43, 95% CI 1.17-1.75, < 0.001) and BD-I subtype (OR = 2.81, 95% CI 2.26-3.50, < 0.001). Analyses on sleep loss triggering low mood were not significant following adjustment for confounders.Gender and bipolar subtype may increase vulnerability to high mood following sleep deprivation. This should be considered in situations where patients encounter sleep disruption, such as shift work and international travel. 10.1192/bjp.bp.117.202259
    Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder. Mu Li,Lin Yezhe,Huang Xingbing,Ning Yuping,Wu Fengchun,Zhang Xiang Yang Human psychopharmacology OBJECTIVE:Sex differences in bipolar disorder are well recognized but little attention has been paid to sex differences in homocysteine or hyperhomocysteinemia in bipolar patients. This study compared gender differences in homocysteine levels and rates of hyperhomocysteinemia in Chinese inpatients with bipolar disorder. METHODS:A total of 198 BD patients and 84 healthy controls were enrolled. The Young Mania Rating Scale, Hamilton Depression Rating Scale, and the Clinical Global Impressions-Severity scale were used to assess the affective symptomatology. Fasting plasma Hcy levels were measured by high-performance liquid chromatography. RESULTS:Men had higher homocysteine levels than women and the prevalence of hyperhomocysteinemia in male patients was approximately twice that in female patients. Logistic regression analyses showed that HHcy was associated with less frequent use of valproate in males and being overweight in females. Further correlation analysis and multivariate regression analysis demonstrated that Hcy levels were inversely correlated with valproate treatment in men and positively associated with overweight in women. CONCLUSIONS:In bipolar patients, there are significant differences between sexes in the levels of homocysteine and prevalence of hyperhomocysteinemia. This appears to be associated with lower prevalence of valproate prescribing in men and with being overweight in women. 10.1002/hup.2724
    Sex differences in rates of obesity in bipolar disorder: postulated mechanisms. Baskaran Anusha,Cha Danielle S,Powell Alissa M,Jalil Dalya,McIntyre Roger S Bipolar disorders OBJECTIVE:The increased standardized mortality ratio (SMR) from cardiovascular disease (CVD) in women with bipolar disorder (BD), relative to men with BD and individuals of both sexes in the general population, provides the impetus to identify factors that contribute to the differential association of obesity with BD in women. METHODS:We conducted a selective PubMed search of English-language articles published from September 1990 to June 2012. The key search terms were bipolar disorder and metabolic syndrome cross-referenced with gender, sex, obesity, diabetes mellitus, hypertension, and dyslipidemia. The search was supplemented with a manual review of relevant article reference lists. Articles selected for review were based on author consensus, the use of a standardized experimental procedure, validated assessment measures, and overall manuscript quality. RESULTS:It is amply documented that adults with BD are affected by the metabolic syndrome at a rate higher than the general population. Women with BD, when compared to men with BD and individuals of both sexes in the general population, have higher rates of abdominal obesity. The course and clinical presentation of BD manifest differently in men and women, wherein women exhibit a higher frequency of depression predominant illness, a later onset of BD, more seasonal variations in mood disturbance, and increased susceptibility to relapse. Phenomenological factors can be expanded to include differences in patterns of comorbidity between the sexes among patients with BD. Other factors that contribute to the increased risk for abdominal obesity in female individuals with BD include reproductive life events, anamnestic (e.g., sexual and/or physical abuse), lifestyle, and iatrogenic. CONCLUSIONS:A confluence of factors broadly categorized as broad- and sex-based subserve the increased rate of obesity in women with BD. It remains a testable hypothesis that the increased abdominal obesity in women with BD mediates the increased SMR from CVD. A clinical recommendation that emerges from this review is amplified attention to the appearance, or history, of factors that conspire to increase obesity in female patients with BD. 10.1111/bdi.12141
    Sex differences in bipolar disorder: Impact of lifetime cannabis use on clinical course, functioning, and quality of life in bipolar disorder. de la Fuente-Tomás Lorena,Arranz Belén,Velasco Angela,Sierra Pilar,Sanchez-Autet Mónica,García-Blanco Ana,Safont Gemma,García-Portilla Maria P Journal of affective disorders BACKGROUND:Cannabis use is markedly prevalent among patients with bipolar disorder (BD). However, to date, there have been no studies on this issue with a sex-based approach. This study examines if lifetime cannabis use (LCU) is differently associated with clinical course, functioning, and quality of life (QoL) in patients with BD by sex. METHODS:Secondary analysis of a cross-sectional, naturalistic, multicentre study. LCU was defined as having had at least one day of use per month for at least 12 consecutive months in a patient's life. RESULTS:A total of 224 patients with BD were included (65.2% women). Patients with LCU were younger (p = 0.001) and had their first hospitalization earlier (p<0.005) than those without LCU, regardless of sex. Among women, LCU was associated with being single (p = 0.006), worse sexual functioning (p = 0.006), financial functioning (p = 0.009), QoL [bodily pain (p = 0.009), vitality (p = 0.027), social functioning (p = 0.037), emotional role (p = 0.038), mental health (p = 0.001), and mental summary component (p = 0.012)]. After controlling for confounders, among women, LCU was associated with worse QoL, specifically on bodily pain (p = 0.049) and mental health (p = 0.016) subscales. Among males, no statistically significant differences were found between LCU and no LCU (NLCU) in any of the variables of the study. LIMITATIONS:This study was a secondary analysis not powered specifically to analyze cannabis use. CONCLUSIONS:LCU was associated with a younger age at first hospitalization in both women and men, while only women reported worse QoL on bodily pain and mental health subscales. Clinicians and public health providers should be aware of this and inform their patients and the general population of these detrimental effects. 10.1016/j.jad.2020.01.043
    Gender differences in health-related quality of life in patients with bipolar disorder. de la Cruz Maria Syl D,Lai Zongshan,Goodrich David E,Kilbourne Amy M Archives of women's mental health Health-related quality of life (HRQOL) is a widely accepted measure of illness state that is related to morbidity and mortality. Findings from various populations show that women report lower HRQOL than men. We analyzed baseline HRQOL data for gender differences from a multisite, randomized controlled study for adults with bipolar disorder. HRQOL was assessed using the 12-item Short Form (SF-12) physical component summary (PCS) and mental component summary (MCS) health scales. Multivariate linear and bivariate regression models examined differences in self-reported data on demographics, depressive symptoms (nine-item Patient Health Questionnaire), bipolar disorder symptoms (Internal State Scale), and medical comorbidities. Out of 384 enrolled (mean age = 42 years), 256 were women (66.7 %). After controlling for sociodemographic characteristics and clinical factors, women had lower SF-12 PCS scores than men [β = -1.78, standard error (SE) = 0.87, p < 0.05], indicating worse physical health, but there were no gender differences in MCS scores. After controlling for patient factors including medical and behavioral comorbidities, the association between gender and PCS score was no longer significant. Of the medical comorbidities, pain was associated with lower PCS scores (β = -4.90, SE = 0.86, p < 0.0001). Worse physical HRQOL experienced by women with bipolar disorder may be explained by medical comorbidity, particularly pain, suggesting the importance of gender-tailored interventions addressing physical health conditions. 10.1007/s00737-013-0351-1
    White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder. Köhler Ole,Sylvia Louisa G,Bowden Charles L,Calabrese Joseph R,Thase Michael,Shelton Richard C,McInnis Melvin,Tohen Mauricio,Kocsis James H,Ketter Terence A,Friedman Edward S,Deckersbach Thilo,Ostacher Michael J,Iosifescu Dan V,McElroy Susan,Nierenberg Andrew A The Australian and New Zealand journal of psychiatry OBJECTIVE:Immune alterations may play a role in bipolar disorder etiology; however, the relationship between overall immune system functioning and mood symptom severity is unknown. METHODS:The two comparative effectiveness trials, the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study (Bipolar CHOICE) and the Lithium Treatment Moderate-Dose Use Study (LiTMUS), were similar trials among patients with bipolar disorder. At study entry, white blood cell count and bipolar mood symptom severity (via Montgomery-Aasberg Depression Rating Scale and Bipolar Inventory of Symptoms Scale) were assessed. We performed analysis of variance and linear regression analyses to investigate relationships between deviations from median white blood cell and multinomial regression analysis between higher and lower white blood cell levels. All analyses were adjusted for age, gender, body mass index, smoking, diabetes, hypertension and hyperlipidemia. RESULTS:Among 482 Bipolar CHOICE participants, for each 1.0 × 10/L white blood cell deviation, the overall Bipolar Inventory of Symptoms Scale severity increased significantly among men (coefficient = 2.13; 95% confidence interval = [0.46, -3.79]; p = 0.013), but not among women (coefficient = 0.87; 95% confidence interval = [-0.87, -2.61]; p = 0.33). Interaction analyses showed a trend toward greater Bipolar Inventory of Symptoms Scale symptom severity among men (coefficient = 1.51; 95% confidence interval = [-0.81, -3.82]; p = 0.2). Among 283 LiTMUS participants, higher deviation from the median white blood cell showed a trend toward higher Montgomery-Aasberg Depression Rating Scale scores among men (coefficient = 1.33; 95% confidence interval = [-0.22, -2.89]; p = 0.09), but not among women (coefficient = 0.34; 95% confidence interval = [-0.64, -1.32]; p = 0.50). When combining LiTMUS and Bipolar CHOICE, Montgomery-Aasberg Depression Rating Scale scores increased significantly among men (coefficient = 1.09; 95% confidence interval = [0.31, -1.87]; p = 0.006) for each 1.0 × 10/L white blood cell deviation, whereas we found a weak association among women (coefficient = 0.55; 95% confidence interval = [-0.20, -1.29]; p = 0.14). Lower and higher white blood cell levels correlated with greater symptom severity and specific symptoms, varying according to gender. CONCLUSION:Deviations in an overall immune system marker, even within the normal white blood cell range, correlated with mood symptom severity in bipolar disorder, mostly among males. Studies are warranted investigating whether white blood cell count may predict response to mood-stabilizing treatment. 10.1177/0004867416644508
    Sex differences in neurocognitive and psychosocial functioning in bipolar disorder. Solé Brisa,Varo Cristina,Torrent Carla,Montejo Laura,Jiménez Esther,Bonnin Caterina Del Mar,Clougher Derek,Verdolini Norma,Amoretti Silvia,Piazza Flavia,Borràs Roger,Pomarol-Clotet Edith,Sáiz Pilar A,García-Portilla Maria P,Vieta Eduard,Martínez-Arán Anabel Journal of affective disorders BACKGROUND:Sex differences influence the clinical characteristics and course of illness of bipolar disorder (BD). OBJECTIVE:Therefore, the aim of the present study was to examine the role of sex differences in neurocognitive performance and psychosocial functioning in a large sample of euthymic patients suffering from BD. METHODS:The sample included 462 individuals, 347 patients with BD (148 males and 199 females) and 115 healthy controls (HC) (45 males and 70 females). Performance on a comprehensive neuropsychological battery assessing six cognitive domains and psychosocial functioning was compared between groups using linear mixed models, with sex and group as main effects, group by sex interactions and center as a random effect. RESULTS:Males performed better than females in working memory (p < 0.001), whereas females outperformed males in the verbal learning (p = 0.03) and memory recognition (p = 0.03) tasks. No significant group by sex interactions were detected in cognitive performance. There were no overall sex differences or group by sex interactions in psychosocial functioning. LIMITATIONS:Lack of assessment of visuo-spatial working memory. CONCLUSIONS:There were no overall sex differences in neurocognition and psychosocial functioning. However, small sex differences in some measures of working memory and verbal memory were found. Individual differences of each patient, including sex perspective, should be considered in order to perform a tailored intervention plan adjusted to specific needs in the context of personalized treatment. 10.1016/j.jad.2021.09.066
    Gender Differences in Complete Blood Count and Inflammatory Ratios among Patients with Bipolar Disorder. Fusar-Poli Laura,Amerio Andrea,Cimpoesu Patriciu,Grimaldi Filioli Pietro,Natale Antimo,Zappa Guendalina,Aguglia Eugenio,Amore Mario,Serafini Gianluca,Aguglia Andrea Brain sciences Evidence suggested that inflammation may be involved in the etiopathogenesis of bipolar disorder (BD), a chronic psychiatric condition affecting around 2-3% of the general population. However, little is known regarding potential gender differences in peripheral biomarkers of BD, such as neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios. In total, 197 females and 174 males with BD in different phases (i.e., (hypo)mania, depression, euthymia) were recruited. A blood sample was drawn to perform a complete blood count (CBC). NLR, PLR, and MLR were subsequently calculated, and differences were computed according to the illness phase and gender. PLR was consistently higher in (hypo)manic than depressed patients, in both males and females. No significant gender differences in PLR value were found when considering only (hypo)mania. Conversely, NLR was increased in (hypo)mania only among males, and gender differences were retrieved in the (hypo)manic subgroup. The findings related to MLR were only marginally significant. Higher platelets values were associated with (hypo)mania only in the female group. Basophils and eosinophils appeared gender- but not state-dependent. Our findings provide further evidence that increased PLR levels may be associated with (hypo)mania in bipolar patients, regardless of gender. Moreover, the usefulness of NLR as a peripheral biomarker of BD appeared limited to males while the role of platelets to females. As CBC represents a low-cost and easily accessible test, researchers should investigate in-depth its potential usefulness as a biomarker of BD and other psychiatric disorders. 10.3390/brainsci11030363
    Gender differences in the treatment of patients with bipolar disorder: a study of 7354 patients. Karanti Alina,Bobeck Christian,Osterman Maja,Kardell Mathias,Tidemalm Dag,Runeson Bo,Lichtenstein Paul,Landén Mikael Journal of affective disorders BACKGROUND:Gender differences in treatment that are not supported by empirical evidence have been reported in several areas of medicine. Here, the aim was to evaluate potential gender differences in the treatment for bipolar disorder. METHODS:Data was collected from the Swedish National Quality Assurance Register for bipolar disorder (BipoläR). Baseline registrations from the period 2004-2011 of 7354 patients were analyzed. Multiple logistic regression analysis was used to study the impact of gender on interventions. RESULTS:Women were more often treated with antidepressants, lamotrigine, electroconvulsive therapy, benzodiazepines, and psychotherapy. Men were more often treated with lithium. There were no gender differences in treatment with mood stabilizers as a group, neuroleptics, or valproate. Subgroup analyses revealed that ECT was more common in women only in the bipolar I subgroup. Contrariwise, lamotrigine was more common in women only in the bipolar II subgroup. LIMITATIONS:As BipoläR contains data on outpatient treatment of persons with bipolar disorder in Sweden, it is unclear if these findings translate to inpatient care and to outpatient treatment in other countries. CONCLUSIONS:Men and women with bipolar disorder receive different treatments in routine clinical settings in Sweden. Gender differences in level of functioning, bipolar subtype, or severity of bipolar disorder could not explain the higher prevalence of pharmacological treatment, electroconvulsive therapy, and psychotherapy in women. Our results suggest that clinicians׳ treatment decisions are to some extent unduly influenced by patients׳ gender. 10.1016/j.jad.2014.11.058
    Effects of resilience on quality of life in patients with bipolar disorder. Lee Dongyun,Cha Boseok,Park Chul-Soo,Kim Bong-Jo,Lee Cheol-Soon,Lee So-Jin,Seo Ji-Yeong,Cho Young Ah,Ha Jong Hun,Choi Jae-Won Journal of affective disorders BACKGROUND:Few studies have examined the effects of resilience on quality of life (QOL) in patients with bipolar disorder (BD). Therefore, this study investigated the association between resilience and QOL in patients with BD and compared it to the relationship between resilience and QOL in healthy individuals. METHODS:Participants were 68 euthymic patients with BD and 68 age-, sex-, and length of education-matched controls. Sociodemographic characteristics and clinical variables of the two groups were obtained using face-to-face interviews, and all participants completed the Connor-Davidson Resilience Scale, the World Health Organization QOL-Brief Form. RESULTS:The QOL of the BD group was significantly impaired compared with that of the controls. Degree of resilience, number of depressive episodes, Clinical Global Impression scores, degree of impulsivity, and length of education were significantly correlated with QOL in the BD group. Resilience was significantly associated with overall QOL, physical subdomains of QOL, psychological subdomains of QOL, social subdomains of QOL, and environmental subdomains of QOL in the BD group, even after controlling for confounders. In the control group, resilience was significantly associated with overall QOL, the physical subdomains of QOL, psychological subdomains of QOL, and social subdomains of QOL. LIMITATIONS:The number of participants in each group was 68, which is a relatively small sample size. CONCLUSIONS:Resilience in patients with BD was independently and positively correlated with various areas of QOL. Various strategies to reinforce resilience in patients with BD are needed to improve the low QOL in this population. 10.1016/j.jad.2016.08.075
    Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder. Schreiter S,Spengler S,Willert A,Mohnke S,Herold D,Erk S,Romanczuk-Seiferth N,Quinlivan E,Hindi-Attar C,Banzhaf C,Wackerhagen C,Romund L,Garbusow M,Stamm T,Heinz A,Walter H,Bermpohl F Psychological medicine BACKGROUND:Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. METHOD:During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. RESULTS:BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. CONCLUSIONS:This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders. 10.1017/S0033291716001963
    The prevalence of bipolar disorder in China: A meta-analysis. Zhang Ling,Cao Xiao-Lan,Wang Shi-Bin,Zheng Wei,Ungvari Gabor S,Ng Chee H,Zhong Bao-Liang,Wang Gang,Xiang Yu-Tao Journal of affective disorders OBJECTIVE:This is a meta-analysis of the prevalence of bipolar disorders (BD) in the general population of China. METHODS:A systematic literature search was conducted via the following databases: PubMed, EMBASE, PsycINFO, China National Knowledge Infrastructure (CNKI), WanFang and SinoMed. Studies on the prevalence of BD in the general population in China were identified. Statistical analyses were performed using the Comprehensive Meta-Analysis program. RESULTS:Altogether 32 studies conducted between 1984 and 2013 with 470,411 participants met the inclusion criteria for the analysis; the median age was 44.6 years and 49.6% of participants were female. The estimated point, 12-month and lifetime prevalence of BD in China were 0.09% (95% Confidence interval [CI]: 0.06-0.12%), 0.17% (95% CI: 0.10-0.29%) and 0.11% (95% CI: 0.07-0.17%), respectively. For BD-I, the estimated point, 12-month and lifetime prevalence rates were 0.06% (95% CI: 0.04-0.10%), 0.08% (95% CI: 0.02-0.30%) and 0.09% (95% CI: 0.05-0.16%), respectively. For BD-II, the estimated point and lifetime prevalence rates were 0.04% (95% CI: 0.02-0.06%) and 0.04% (95% CI: 0.02-0.09%), respectively. The 12-month prevalence of BD before the year 2010 was significantly lower than that after 2010 (0.12% vs. 0.26%, P=0.04). Meta-regression analysis revealed that younger age was significantly associated with higher 12-month prevalence of BD (coefficient=0.096, 95% CI: 0.027, 0.164, P=0.006). CONCLUSION:This first meta-analysis of the pooled prevalence of BD in China found that rates are generally lower than those reported in Western countries. Future studies with more rigorous and refined methodology are needed. 10.1016/j.jad.2016.08.062
    Sex differences of hippocampal structure in bipolar disorder. Shi Jing,Guo Hua,Fan Fengmei,Fan Hongzhen,An Huimei,Wang Zhiren,Tan Shuping,Yang Fude,Tan Yunlong Psychiatry research. Neuroimaging Although differential patterns in clinical characteristics have been consistently noted between male and female patients with bipolar disorder (BD), the effect of sex on the hippocampal structure remains unclear. To address this, the present study investigated the effects of BD and sex on the hippocampal structure, and the relationship between the hippocampal structure and cognitive performance. Morphometric and neurocognitive analyses were performed in 91 subjects (patients with BD: male/female = 33/19; normal controls: male/female = 22/17). Patients had significantly decreased left parahippocampal gyrus area and left/right hippocampal volume compared to normal controls. Within the BD group only, female patients presented with smaller right hippocampal volume than males. In the Spatial Span (SS) test (used to assess working memory capacity) and the Maze test (used to evaluate the ability to anticipate), patients demonstrated decreased performance compared to normal controls, with a significant main effect of sex. Left parahippocampal gyrus area and right hippocampal volume were positively correlated with SS and Maze in patients; moreover, right hippocampal volume predicted 17.4% of SS performance variance. These results suggest that there may be a difference between male and female patients with regard to right hippocampal volume, and that female patients may need more attention than males. 10.1016/j.pscychresns.2017.11.011
    Gender-related differences in patients with bipolar disorder: a nationwide study. Buoli Massimiliano,Cesana Bruno Mario,Dell'Osso Bernardo,Fagiolini Andrea,de Bartolomeis Andrea,Bondi Emi,Maina Giuseppe,Bellomo Antonello,Altamura A Carlo CNS spectrums OBJECTIVE:The possible presence of gender-related differences in patients with bipolar disorder (BD) may have diagnostic and therapeutic implications. This multicenter study aimed to investigate gender differences in BD in the largest Italian database collected to date, on behalf of the Italian Chapter of the International Society of Bipolar Disorders. METHODS:A total of 1674 patients (males: n = 714; females: n = 960) from different psychiatric departments were compared according to gender on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (gender) at the univariate analyses, preliminary multiple logistic regression analyses were performed. A final multivariable logistic regression was then performed, considering gender as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. RESULTS:The results of the final multivariable logistic regression analysis with previous statistically significant demographic and clinical variables were the following: female gender was less frequently associated with employment (odds ratio [OR] = 0.7, P < 0.01), lifetime single marital status (OR = 0.45, P < 0.01), and substance abuse in the last year (OR = 0.35, P < 0.01), whereas it was more frequently associated with a major number of lifetime major depressive episodes (OR = 1.78, P < 0.01) and psychiatric visits in the last year (OR = 1.38, P = 0.01). CONCLUSION:Few significant differences were found between genders in BD, particularly for those clinical features that are associated with poor prognosis (substance abuse for males and number of depressive episodes for females). Transcultural studies are needed to identify cultural versus illness-related variables possibly explaining the different clinical presentation of BD in relation to gender. 10.1017/S1092852918001529
    Gender differences in the association between physical activity and cognitive function in individuals with bipolar disorder. Fellendorf F T,Kainzbauer N,Platzer M,Dalkner N,Bengesser S A,Birner A,Queissner R,Rauch P,Hamm C,Pilz R,Reininghaus E Z Journal of affective disorders INTRODUCTION:Bipolar disorder (BD) is accompanied by a high number of comorbidities and associated with an overall increased mortality. Especially obesity, systemic inflammatory processes and cognitive deficits are highly prevalent and increase with the course of illness. Physical activity (PA) is associated with beneficial effects on somatic comorbidities such as obesity or cardiovascular disease in individuals without psychiatric disorder. Furthermore, PA might increase neurocognitive performance and reduce systemic inflammation. OBJECTIVE:The aim of the study was to investigate the association between PA and neurocognitive function in euthymic individuals suffering from BD. METHODS AND PARTICIPANTS:120 individuals with BD, euthymic at test time, completed the self-reported International Physical Activity Questionnaire (IPAQ) assessing PA of the past seven days and were accordingly assigned to a specific activity category (low, moderate or vigorous). Furthermore, clinical parameters were gathered and cognitive tests analysing verbal-dependent intelligence, attention, executive functioning as well as memory were administered. RESULTS:Female individuals in the vigorous PA group performed significantly higher in most of the cognitive domains compared to females with moderate or low PA. In males, we only found a significant difference in one test for attention between moderate/vigorous and the low activity group. CONCLUSION:Differences between PA groups in cognitive performance in female individuals with BD were obvious in almost all cognitive domains. As cognitive deficits are strongly associated with a worse course of disease and outcome, PA might offer a concomitant therapy targeting not only somatic comorbidities such as obesity and cardiovascular disease, but also neurocognition. 10.1016/j.jad.2017.06.048