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Importance: Little is known about differences between Black and White women with respect to the prevalence of postpartum mood disorders or symptom presentations., Objective: To determine the prevalence and characteristics of postpartum major mood disorders in Black and White women at 4-6 weeks after birth., Methods: This is a secondary analysis of a large-scale study designed to screen women for postpartum depression with the Edinburgh Postnatal Depression Scale (EPDS) and collect symptom data. Data were collected at an urban maternity hospital in an academic setting in Pittsburgh, Pennsylvania. Of the 2,019 women who screened positive and accepted a psychiatric diagnostic interview, 163 and 85 Black women had major depressive and bipolar disorders, respectively, and 508 and 177 White women had major depressive and bipolar disorders, respectively. Those with an EPDS score greater than or equal to 10 were offered a psychiatric assessment (in-person at home or by telephone) with the Structured Clinical Interview for DSM IV using the Structured Interview Guide for the Hamilton Rating Scale for Depression, Atypical Depression Version symptom inventory, a questionnaire related to childhood and adulthood physical and sexual abuse, and the Short Form Survey 12. Participants who self-identified as Black or White were included in this analysis., Results: Among screen-positive participants, no significant difference in the rate of major depressive disorder (40% Black and 35% White) was observed. However, bipolar disorder significantly differed between Black (19.2%) and White (11.5%) women. Additionally, symptom profiles differed between Black and White participants with major depressive disorder, and a high rate of traumatic experiences was reported by participants with major depression and bipolar disorder in both racial groups., Conclusion: An understanding of the different presentations of postpartum mood disorders between Black and White women, as well as trauma-informed care, can optimize postpartum health care through supporting advocacy efforts for resource allocation and health care delivery., Trial Registration: Dataset from study at ClinicalTrials.gov identifier: NCT00282776., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Background: There is limited evaluation of approaches to identify patients with new onset bipolar affective disorder (BPAD) when using administrative datasets., Methods: Using the Massachusetts All-Payer Claims Database (APCD), we identified individuals with a 2016 diagnosis of bipolar disorder with mania and examined patterns of psychiatric and medical care over the preceding 48 months., Results: Among 4806 individuals aged 15-35 years with a 2016 BPAD with mania diagnosis, 3066 had 48 months of historical APCD data, and of those, 75 % involved information from ≥2 payors. After excluding individuals with historical BPAD or mania diagnoses, there were 583 individuals whose 2016 BPAD with mania diagnosis appeared to be new (i.e., 34 new diagnoses per 100,000 individuals aged 15-35 years). Most individuals received medical care, e.g., 98 % had outpatient visits, 76 % had Emergency Department (ED) visits, and 50 % had mental health-related ED visits during the 48 months prior to their first mania diagnosis. One-third (37.2 %) had a depressive episode before their initial BPAD with mania diagnosis., Limitations: Study was conducted in one state among insured individuals. We used administrative data, which permits evaluation of large populations but lacks rigorous, well-validated claims-based definitions for BPAD. There could be diagnostic uncertainty during illness course, and clinicians may differ in their diagnostic thresholds., Conclusions: Careful examination of multiple years of patient history spanning all payors is essential for identifying new onset BPAD diagnoses presenting with mania, which in turn is critical to estimating population rates of new disease and understanding the early course of disease., Competing Interests: Declaration of competing interest Dr. Benson reports volunteering for the Epic Behavioral Health Specialty Steering Board. Dr. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with options), and has received grant support from Biogen, Inc. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. Dr. Hsu consults for Cambridge Health Alliance, Brandeis University, University of Southern California, and Columbia University, and has received compensation for keynote speeches from the University of South Carolina and Invitrx., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Hypothesis: Breast cancer is more prevalent in women with severe mental illness than in the general population, and use of prolactin-increasing antipsychotics may be a contributing factor., Study Design: A nested case-control study was conducted using the Swedish nationwide registers (inpatient/outpatient care, sickness absence, disability pension, prescribed drugs, cancers). All women aged 18-85 years with schizophrenia/schizoaffective/other nonaffective psychotic disorder/bipolar disorder and breast cancer (cases) were matched for age, primary psychiatric diagnosis, and disease duration with five women without cancer (controls). The association between cumulative exposure to prolactin-increasing/prolactin-sparing antipsychotics and breast cancer was analyzed using conditional logistic regression, adjusted for comorbidities and co-medications., Study Results: Among 132 061 women, 1642 (1.24%) developed breast cancer between 2010 and 2021, at a mean age of 63.3 ± 11.8 years. Compared with 8173 matched controls, the odds of breast cancer increased in women with prior exposure to prolactin-increasing antipsychotics for 1-4 years (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.03-1.41), and for ≥ 5 years (aOR = 1.47, 95%CI = 1.26-1.71). There were no increased or decreased odds of breast cancer with exposure to prolactin-sparing antipsychotics of either 1-4 years (aOR = 1.17, 95%CI = 0.98-1.40) or ≥5 years (aOR = 0.99, 95%CI = 0.78-1.26). The results were consistent across all sensitivity analyses (ie, according to different age groups, cancer types, and primary psychiatric diagnosis)., Conclusions: Although causality remains uncertain, exposure to prolactin-elevating antipsychotics for ≥ 1 year was associated with increased odds of breast cancer in women with severe mental illness. When prescribing antipsychotics, a shared decision-making process should consider individual risk factors for breast cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: This study explores among individuals with a major depressive episode (MDE) the potential impact of mixed features on the risk of suicide attempt, suicidal thoughts, self-harm intentions, and thoughts of death., Methods: Data from the French Mental Health in General Population (MHGP) survey (1999-2003) were analyzed, including 128 participants meeting DSM 5 criteria for MDE with mixed features (MDE with at least 3 manic symptoms) and 3,312 participants experiencing MDE without mixed features. Our primary analysis focused on suicide attempt, with additional examination of recent suicidal thoughts, self-harm intentions, and thoughts of death. Multivariable regression models were performed to adjust for potential confounding variables, including sociodemographics, previous suicide attempt, number of depressive symptoms, and psychiatric comorbidity., Results: MDE with mixed features was significantly associated with an increased risk of suicide attempt (adjusted odds ratio [AOR] = 1.69; 95% CI, 1.26-2.25). This association did not significantly differ between men and women. Furthermore, the number of manic symptoms demonstrated a dose-dependent relationship with an increased risk of suicide attempt (AOR = 1.18; 95% CI, 1.07-1.30; P < .001). Mixed features were also associated with suicide attempt among individuals with MDE and without recent suicidal thoughts (AOR = 2.74; 95% CI, 1.36-5.54)., Conclusion: This study underscores the importance of assessing mixed features when evaluating the risk of suicide attempt in individuals with MDE. Mechanisms underlying this association might be independent of progression from thoughts of death to suicidal thoughts, suicidal intention, and ultimately, suicide attempt., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Introduction: Pharmacoepidemiological data suggest that lithium prescriptions for bipolar disorder are gradually decreasing, with less attention having been paid to other indications., Methods: We examined lithium prescriptions between 1994 and 2017 in data provided by the Drug Safety in Psychiatry Program AMSP, including psychiatric hospitals in Germany, Austria and Switzerland. We compared lithium use for different diagnoses before and after 2001 and in three periods (T1: 1994-2001, T2: 2002-2009, and T3: 2010-2017)., Results: In a total of 158,384 adult inpatients (54% female, mean age 47.4±17.0 years), we observed a statistically significant decrease in lithium prescriptions between 1994-2000 and 2001-2017 in patients with schizophrenia spectrum disorder from 7.7% to 5.1% and in patients with affective disorders from 16.8% to 9.6%. Decreases in use were also observed for diagnostic subgroups: schizoaffective disorder (ICD-10 F25: 27.8% to 17.4%), bipolar disorder (F31: 41.3% to 31%), depressive episode (F32: 8.1% to 3.4%), recurrent depression (F33: 17.9% to 7.5%, all: p<0.001) and emotionally unstable (borderline) personality disorder (6.3% to 3.9%, p=0.01). The results in T1 vs. T2 vs. T3 were for F25: 26.7% vs. 18.2% vs. 16.2%, F32: 7.7% vs. 4.2% vs. 2.7%, F33: 17.2% vs. 8.6% vs. 6.6% and for F31: 40.8% vs. 31.7% vs 30.0%, i. e. there was no further decrease for lithium use in bipolar disorder after 2002. Lithium's main psychotropic co-medications were quetiapine (21.1%), lorazepam (20.6%), and olanzapine (15.2%)., Discussion: In inpatients, the use of lithium has decreased in patients with bipolar disorder and also with various other psychiatric diagnoses., Competing Interests: Competing interests S. Toto is the project manager of the AMSP program and a member of the advisory board for Otsuka and Janssen-Cilag and has received speaker’s honoraria from Janssen-Cilag, Lundbeck/Otsuka, Recordati Pharma GmbH, ROVI, and Servier. G. Schoretsanitis has served as a consultant for Dexcel Pharma, HLS Therapeutics, Saladax and Thermo Fisher and has received speaker’s fees from HLS Therapeutics and Saladax. M. de Bardeci is Co-Founder and member of the board of directors of the company DeepPsy AG. All other authors state they have no conflicts of interest to declare.Role of the funding sourceThe authors did not receive any specific grants or funding for the present study. The AMSP drug safety program is facilitated by nonprofit associations in Germany, Austria and Switzerland. The AMSP program has been supported with unrestricted educational and research grants since 1993 by the following companies: Austrian companies: Astra Zeneca Österreich GmbH, Boehringer Ingelheim Austria, Bristol-Myers Squibb GmbH, CSC Pharmaceuticals GmbH, Eli Lilly GmbH, Germania Pharma GmbH, GlaxoSmithKline Pharma GmbH, Janssen-Cilag Pharma GmbH, Lundbeck GmbH, Novartis Pharma GmbH, Pfizer Med Inform and Wyeth Lederle Pharma GmbH; German companies: Abbott GmbH & Co. KG, Aristo Pharma, AstraZeneca GmbH, Aventis Pharma Deutschland GmbH GE–O/R/N, Bayer Vital GmbH, Boehringer Mannheim GmbH, Bristol-Myers-Squibb, Ciba Geigy GmbH, Desitin Arzneimittel GmbH, Duphar Pharma GmbH & Co. KG, Eisai GmbH, Esparma GmbH Arzneimittel, GlaxoSmithKline Pharma GmbH & Co. KG, Hoffmann-La Roche AG Medical Affairs, Janssen-Cilag GmbH, Janssen Research Foundation, Knoll Deutschland GmbH, Lilly Deutschland GmbH Niederlassung Bad Homburg, Lundbeck GmbH & Co. KG, Novartis Pharma GmbH, Nordmark Arzneimittel GmbH, Organon GmbH, Otsuka-Pharma Frankfurt, Pfizer GmbH, Pharmacia & Upjohn GmbH, Promonta Lundbeck Arzneimittel, Recordati Pharma GmbH, Rhone-Poulenc Rohrer, ROVI, Sanofi-Synthelabo GmbH, Sanofi-Aventis Deutschland, Schering AG, SmithKlineBeecham Pharma GmbH, Solvay Arzneimittel GmbH, Synthelabo Arzneimittel GmbH, Dr. Wilmar Schwabe GmbH & Co., Thiemann Arzneimittel GmbH, Troponwerke GmbH & Co. KG, Upjohn GmbH, Wander Pharma GmbH and Wyeth-Pharma GmbH; Swiss companies: AHP (Schweiz) AG, AstraZeneca AG, Bristol-Myers Squibb AG, Desitin Pharma GmbH, Eli Lilly (Suisse) S.A., Essex Chemie AG, GlaxoSmithKline AG, Janssen-Cilag AG, Lundbeck (Suisse) AG, Organon AG, Pfizer AG, Pharmacia, Sanofi-Aventis (Suisse) S.A., Sanofi-Synthelabo SA, Servier SA, SmithKlineBeecham AG, Solvay Pharma AG, Wyeth AHP (Suisse) AG and Wyeth Pharmaceuticals AG., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aims: To estimate the strength of association between psychiatric disorders and substance use disorders (SUD), and cannabis use and cannabis use disorder (CUD) during early pregnancy., Design: Observational study., Setting: Kaiser Permanente Northern California, USA., Participants: 299 496 pregnancies from 227 555 individuals screened for cannabis use by self-report and a urine toxicology test at entrance to prenatal care in Kaiser Permanente Northern California during January 2011-December 2021 (excepting year 2020). The sample was 62.5% non-White, with a mean (standard deviation) age of 31.1 (5.5) years; 6.8% used cannabis; 0.2% had a CUD., Measurements: Exposure variables included electronic health record-based psychiatric diagnoses of attention deficit hyperactivity, anxiety, bipolar, depressive, personality, posttraumatic stress and psychotic disorders; and alcohol, opioid, stimulant and tobacco use disorders, during the two years prior to pregnancy up to the day before the prenatal substance use screening date. Outcome variables were any cannabis use, frequency of self-reported cannabis use and CUD during early pregnancy., Findings: Psychiatric disorder prevalence ranged from 0.2% (psychotic) to 14.3% (anxiety), and SUD ranged from 0.3% (stimulant/opioid) to 3.8% (tobacco). Psychiatric disorders were associated with cannabis use and CUD, with the strongest association for any use found for bipolar disorder (adjusted odds ratio [aOR] = 2.83; 95% confidence interval [CI] = 2.53-3.17) and the strongest association for CUD found for psychotic disorders (aOR = 10.01, 95% CI = 6.52-15.37). SUDs were associated with cannabis use and CUD, with the strongest association for any use found for tobacco use disorder (aOR = 4.03, 95% CI = 3.82-4.24) and the strongest association for CUD found for stimulant use disorder (aOR = 21.99, 95% CI = 16.53-29.26). Anxiety, bipolar, depressive disorders and tobacco use disorder were associated with greater odds of daily than monthly or less cannabis use., Conclusions: Psychiatric disorders and substance use disorders appear to be associated with elevated odds of any and frequent cannabis use as well as cannabis use disorder during early pregnancy. In most cases, the associations with cannabis outcomes were stronger for substance use disorders than other psychiatric disorders., (© 2024 Society for the Study of Addiction.)

Background: Substantial observational evidence suggests an association between neuropsychiatric conditions and venous thromboembolism (VTE). However, the causal relationship between these two conditions requires further investigation. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the bidirectional causal effects between four neuropsychiatric conditions and VTE, deep vein thrombosis, and pulmonary embolism (PE)., Methods: Genetic variants associated with four neuropsychiatric conditions (ie, schizophrenia, major depressive disorder [MDD], bipolar disorder, and epilepsy) and VTE, deep vein thrombosis, and PE were selected. Bidirectional univariable and multivariable MR methods were applied to evaluate the causal relationships among these conditions. The primary causal estimates were obtained using the inverse variance weighted method with multiplicative random effects, supplemented by MR Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analysis was conducted using the MR pleiotropy residual sum, funnel plots, and outlier (MR pleiotropy and residual sum and outlier) method., Results: Univariable MR results showed that genetic susceptibility to MDD increases the risk of VTE and PE (VTE: odds ratio [OR], 1.25; 95% confidence interval [CI], 1.08-1.46; P = .004; PE: OR, 1.36; 95% CI, 1.09-1.69; P = .006) and that PE has an adverse causal effect on MDD (OR, 1.02; 95% CI, 1.00-1.04; P = .026). Adjustment for confounders such as obesity, sleep duration, smoking, physical activity, and alcohol consumption revealed that increased genetic susceptibility to MDD is also associated with VTE and PE., Conclusions: Our results suggest that genetic susceptibility to MDD might have an adverse causal effect on the risk of VTE and PE and that PE has a reverse causal effect on MDD. Prevention and early diagnosis of depression are crucial in the management of VTE and PE., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome., Methods: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses., Results: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort., Limitations: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends., Conclusions: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear., Methods: A cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6-7), intermediate (scores 4-5), or unfavorable (scores 0-3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD., Results: During the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76-3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83-3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14-9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40-3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16-0.58)., Conclusions: Our findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The burden of major depressive disorder is compounded by a limited understanding of its risk factors, the limited efficacy of treatments, and the lack of precision approaches to guide treatment selection. The Texas Resilience Against Depression (T-RAD) study was designed to explore the etiology of depression by collecting comprehensive socio-demographic, clinical, behavioral, neurophysiological/neuroimaging, and biological data from depressed individuals (D2K) and youth at risk for depression (RAD)., Methods: This report details the baseline sociodemographic, clinical, and functional features from the initial cohort (D2K N = 1040, RAD N = 365)., Results: Of the total T-RAD sample, n = 1078 (76.73 %) attended ≥2 in-person visits, and n = 845 (60.14 %) attended ≥4 in-person visits. Most D2K (84.82 %) had a primary diagnosis of any depressive disorder, with a bipolar disorder diagnosis being prevalent (13.49 %). RAD participants (75.89 %) did not have a psychiatric diagnosis, but other non-depressive diagnoses were present. D2K participants had 9-item Patient Health Questionnaire scores at or near the moderate range (10.58 ± 6.42 > 24 yrs.; 9.73 ± 6.12 10-24 yrs). RAD participants were in the non-depressed range (2.19 ± 2.65). While the age ranges in D2K and RAD differ, the potential to conduct analyses that compare at-risk and depressed youth is a strength of the study. The opportunity to examine the trajectory of depressive symptoms in the D2K cohort over the lifespan is unique., Limitations: As a longitudinal study, missing data were common., Conclusion: T-RAD will allow data to be collected from multiple modalities on a clinically well-characterized sample. These data will drive important discoveries on diagnosis, treatment, and prevention of depression., Competing Interests: Declaration of competing interest Madhukar H. Trivedi has provided consulting services to Acadia Pharmaceuticals, Alkermes Inc., Alto Neuroscience Inc., Axsome Therapeutics, Biogen MA Inc., Cerebral Inc., Circular Genomics Inc., Compass Pathfinder Limited, GH Research, GreenLight VitalSign6 Inc., Heading Health, Janssen Pharmaceutical, Legion Health, Merck Sharp & Dohme Corp., Mind Medicine Inc., Myriad Neuroscience, Naki Health Ltd., Navitor, Neurocrine Biosciences Inc., Noema Pharma AG, Orexo US Inc., Otsuka America Pharmaceutical Inc., Perception Neuroscience Holdings, Pharmerit International, Policy Analysis Inc., Praxis Precision Medicines Inc., PureTech LYT Inc., Relmada Therapeutics Inc., Rexahn Pharmaceuticals, Inc., SAGE Therapeutics, Signant Health, Sparian Biosciences, Titan Pharmaceuticals, Takeda Pharmaceuticals Inc., WebMD. He has received grant/research funding from NIMH, NIDA, NCATS, American Foundation for Suicide Prevention, Patient-Centered Outcomes Research Institute (PCORI), and Blue Cross Blue Shield of Texas. Additionally, he has received editorial compensation from Engage Health Media, and Oxford University Press. Manish K. Jha has received contract research grants from Acadia Pharmaceuticals, Neurocrine Bioscience, Navitor/Supernus and Janssen Research & Development; educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network; consultant fees from Eleusis Therapeutics US, Inc., Janssen Global Services, Janssen Scientific Affairs, Worldwide Clinical Trials/Eliem and Inversargo, Boehringer Ingelhein, and Guidepoint Global; and honoraria from North American Center for Continuing Medical Education, Medscape/WebMD, Clinical Care Options, and Global Medical Education. Thomas Carmody has served as a consultant for Alkermes, Inc. Jane A. Foster has served on the Scientific Advisory Board for MRM Health NL and has received consulting/speaker fees from Klaire Labs, Takeda Canada and Rothman, Benson, Hedges Inc. Joshua S. Elmore, Cherise Chin Fatt, Sangita Sethuram, Tianyi Wang, Taryn L. Mayes, and Abu Minhajuddin do not have any declarations., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Background and aim: obesity is a very important problem in individuals with bipolar disorder. The study was aimed to determine the prevalence of obesity in individuals with bipolar disorder and to evaluate the effects of factors affecting eating behavior such as mindful eating, impulsivity and eating disorders on the development of obesity in these individuals. Methods: this study is a cross-sectional study. A total of 109 individuals (52 female; 57 male) with bipolar disorder who were in a euthymic state at the time of the interview and underwent outpatient follow-up, treatment and monitorization, and 109 age- and sex-matched healthy individuals as the control group were included in the study. The Mindful Eating Questionnaire-30 (MEQ-30), Three-Factor Eating Questionnaire (TFEQ-21), Barratt Impulsiveness Scale 11-Short Form (BIS-11-SF), and Eating Attitude Test-26 (EAT-26) were used, and anthropometric measurements (height, bodyweight, etc.) were taken. Results: the obesity rate was 50.4 % among the cases and 24.8 % in the control group. Moreover, disinhibition (3.4 ± 0.93), emotional eating (3.5 ± 1.13), and mindfulness (2.6 ± 0.54) scores of individuals with BD were significantly lower than for healthy individuals (3.7 ± 0.82, 4.0 ± 0.93, 2.8 ± 0.55, respectively). The risk of obesity was 5.19 times higher in cases compared to the age- and gender-matched controls (OR = 5.19, 95 % CI (2.01-13.37), p = 0.001). The risk of obesity was 2.76 times higher in those with low mindful eating level (OR = 2.76, 95 % CI (1.07-5.47), p = 0.014) and 4.29 times higher in those using antipsyhotics/mood stabilizers (OR = 4.29, 95 % CI (1.12-12.24), p < 0.001). Conclusion: A comprehensive education program on mindful eating and healthy eating would be helpful in elucidating the mechanisms of the possible relationships between bipolar disorder-specific risk factors and mindful eating.

Background: In the current literature the influence of sex on the clinical presentation of the bipolar disorder (BD) in adults has been indicated. It was of the interest whether such a phenomenon is also present in the pediatric population., Methods: The authors collected retrospective clinical data in 288 patients hospitalized on the psychiatry ward aged 10-17 years; 80.2 % females and 19.8 % males., Results: No sex differences were observed in the age of onset, the time from the onset of symptoms to the diagnosis of BD, the number of symptoms during hospital stay, or family history of psychiatric disorder (U Mann-Whitney's p > 0.05). In males the most frequently recorded first episode of BD was mania or hypomania (51 %), and in females, a depressive episode (51 %). The main reason for the hospitalization in boys was episodes of mania (63 %), then mixed episodes (30 %), and depression (7 %). Whereas girls were most often hospitalized due to mixed episodes (52 %), less frequently depression (22 %), and mania (26 %). Co-morbid psychiatric disorders were found more often in boys than in girls (63 % vs 45 %; χ 2 p-value>0.05). The co-occurrence of the dissocial personality, borderline, tic disorders, pervasive developmental disorders and hyperkinetic disorders was different in both sexes., Limitations: The main limitations of the study are the very high proportion of female subjects and the retrospective character of the study., Conclusions: It seems that the clinical presentation of BD in the pediatric population can somewhat depend on the sex of the patients., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Childhood trauma, including emotional neglect, emotional abuse, physical abuse, and sexual abuse, may contribute to borderline personality features like affective instability, identity problems, negative relationships, and self-harm. This study aims to explore how different types of childhood trauma affect these features in bipolar versus unipolar depressive disorders., Methods: We included 839 participants of the Netherlands Study of Depression and Anxiety (NESDA) with a lifetime diagnosis of major depressive disorder single episode (MDDS; N = 443), recurrent major depressive disorder (MDD-R; N = 331), or bipolar disorder (BD; N = 65). Multivariate regression was used to analyze data from the Childhood Trauma Interview and borderline features (from the self-report Personality Assessment Inventory)., Results: On average, participants were 48.6 years old (SD: 12.6), with 69.2 % being women, and 50.3 % of participants assessed positive for childhood trauma. Adjusted analyses revealed that participants diagnosed with BD, followed by MDD-R, exhibited the highest number of borderline personality features. Additionally, within the entire group, a strong association was found between childhood trauma, especially emotional neglect, and the presence of borderline personality features., Conclusion: Given the high prevalence of childhood trauma and borderline personality features, screening for these factors in individuals with mood disorders is crucial. Identifying these elements can inform and enhance the management of the often fluctuating and complex nature of these comorbid conditions, leading to more effective and tailored treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Youth with a family history of bipolar disorder (At-Risk) have a higher risk of developing psychiatric disorders and experiencing environmental stressors than youth without such family history (Control). We studied the differential associations of familial and environmental factors on developing psychiatric diagnoses and symptoms, in At-Risk and Control youth., Methods: At-Risk and Control youth (N = 466, ages 9-22) were systematically assessed for severity of symptoms, psychiatric diagnoses, and self-reported measures of stress and social support. We tested the association of family history and measures of stress or support with symptom severity and diagnoses., Results: At-Risk youth had higher symptom severity scores and were more frequently diagnosed with psychiatric disorders (all p values < 0.001). When predicting mood symptom severity, family history had an interaction effect with stressful life events (p < 0.001) and number of distinct traumatic events (p = 0.001). In multivariate models, At-Risk status predicted anxiety disorders (OR = 2.7, CI 1.3-5.4, p = 0.005) and anxiety severity (Coefficient = 0.4, CI 0.2-0.7, p < 0.001) but not mood or behavioral disorder diagnoses or severity., Limitations: Measures of stress and social support were based on self-report. Not all participants had passed through the period of risk for developing the outcomes under study and the follow up period was variable. We could not fully study the differential impact of physical or sexual abuse due to low frequency of occurrence in controls., Conclusion: At-Risk youth exhibit more severe mood symptoms compared to Controls when exposed to similar levels of stress or trauma. At-Risk youth are also more prone to develop anxiety which may be a precursor for bipolar disorder., Competing Interests: Declaration of competing interest Masoud Kamali has nothing to disclose. Emma K. Stapp has nothing to disclose. Janice M. Fullerton has received honoraria from Illumina for contribution to a Speakers Bureau in 2023 and had flight and accommodations paid for by Novo Nordisk Fonden to attend the Familial High Risk Summit. Neera Ghaziuddin has nothing to disclose. Leslie Hulvershorn has nothing to disclose. Melvin G. McInnis has received research support from Janssen Pharmaceuticals. Philip B. Mitchell has received remuneration from Janssen (Australia) for lectures and advisory board membership in the last 3 years. Gloria Roberts has nothing to disclose. Holly C. Wilcox has nothing to disclose. John I. Nurnberger Jr. has nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Despite the distinctly high risk of suicide among patients with psychiatric disorders, little is known regarding the nationwide rates and risk factors for suicide among individual subgroups of patients with psychiatric disorders. This study aimed to assess differences in suicide rates and identify risk factors for suicide across multiple psychiatric diseases using data from a nationally representative cohort in Korea., Methods: Six groups of incident patients with psychiatric disorders, namely those with drug use disorder (DUD), alcohol use disorder (AUD), schizophrenia (SCZ), bipolar disorder (BD), depressive disorder (DD), or other affective disorders (OADs), were extracted from the National Health Information Database and followed up. Suicide rates and risk factors were then determined for each disease group., Results: Patients with psychiatric disorders had higher suicide rates than did the general population, with standardized mortality ratios (SMRs) ranging from 2.5 to 16.6. In particular, patients with DUD showed markedly higher suicide rate (584.0 per 100,000 person-years [PYs]; SMR, 16.6) than did patients with affective disorders, including DD (119.8 per 100,000 PYs; SMR, 3.1). AUD, DUD, SCZ, and BD showed lower male/female suicide rate ratios (1.1-1.4) than did depressive and OADs (2.2-2.4). Old age increased the risk for suicide among those with DUD and OADs, while medical aid recipients exhibited the lowest suicide risk among those with the AUD and SCZ. Male sex and the presence of multiple psychiatric comorbidities were consistently identified as suicide risk factors across mental illness subgroups., Conclusion: The current study observed substantial variations in suicide rates and risk factors across psychiatric disorders and patient characteristics, which have significant implications for suicide prevention strategies., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: This study examined psychiatric hospitalisation patterns in San Salvatore Hospital in L' Aquila (Italy), during two major crises: the 2009 earthquake and the COVID-19 pandemic lockdown. The investigation spans two four-year periods, from 2008 to 2011 and from 2019 to 2022, with a focus on the trimester around the earthquake and the first wave/lockdown of the pandemic., Methods: We analysed weekly psychiatric unit admissions of adults diagnosed with schizophrenia spectrum disorder, major depression, bipolar disorder, and alcohol/substance use disorder. Four-year periods around the Earthquake and COVID-19 Lockdown were divided into sixteen trimesters, and Generalised linear models were used to analyse the relationship between weekly hospitalisation frequency and trimesters by diagnosis using a Poisson distribution., Results: A total of 1195 and 1085 patients were admitted to the psychiatric ward in the 2008-2011 and 2019-2022 periods, respectively. Weekly hospitalisations in the earthquake trimester were lower than during the previous one for all diagnoses (schizophrenia spectrum: -41.9%, p = 0.040; major depression: -56.7%, p = 0.046; bipolar disorder: -69.1%, p = 0.011; alcohol/substance use disorder: -92.3%, p = 0.013). This reduction persisted for 21, 18, and 33 months after the earthquake for schizophrenia spectrum, bipolar, and alcohol/substance use disorders, respectively. Contrarily, patterns of weekly admissions around the COVID-19 lockdown remained substantially stable in the short term. However, a consistent long-term hospitalisation increase for all diagnoses characterised the first half of 2022 (the cessation of anti-COVID-19 measures; schizophrenia spectrum: +68.6%, p = 0.014; major depression: +133.3%, p = 0.033; bipolar disorder: +180.0%, p = 0.034; alcohol/substance use disorder: +475.0%, p = 0.001)., Conclusions: The present study indicated that exposure to major health crises can have both short- and long-term effects on psychiatric ward admission, holding significant implications for current and future major health emergency management strategies., (© 2024. The Author(s).)

Objective: Amphetamine prescribing has increased in the United States in recent years. Previous research identified an increased risk of incident psychosis with prescription amphetamines. The purpose of this study was to examine the impact of dose levels of prescription amphetamines on the risk of this rare but serious adverse outcome., Methods: A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with past-month exposure to prescription amphetamines. Case subjects were patients ages 16-35 hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control subjects were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety. Amphetamine doses were converted to dextroamphetamine equivalents and divided into terciles. Secondary analyses evaluated the odds of psychosis or mania with methylphenidate use., Results: Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use (adjusted odds ratio=2.68, 95% CI=1.90-3.77). A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use (adjusted odds ratio=0.91, 95% CI=0.54-1.55)., Conclusions: Although use of hospitalized control subjects excludes individuals with less severe disease, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania., Competing Interests: Dr. Moran is employed by Sage Therapeutics. Dr. Perlis has served as a scientific adviser for Alkermes, Belle Artificial Intelligence, Burrage Capital, Circular Genomics, Genomind, Mila Health, Psy Therapeutics, Swan AI Studios, and Vault Health. Dr. Ongur has received honoraria from Boehringer Ingelheim, Guggenheim LLC, and Neumora for scientific presentations. The other authors report no financial relationships with commercial interests.

Although several studies have examined a diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BD), only a few studies specifically focused on adolescents and young adults who are at the peak ages of BD onset. Data from participants (N = 130,793) aged 10-29 years who were diagnosed with MDD were extracted from the Taiwan National Health Insurance Research Database. We applied demographic analyses, survival analysis, Aalen Johansen curves, and Cox regression, investigating the diagnostic conversion rate and factors that were most or less predictive of conversion. Among the adolescents and young adults with MDD, the number of participant conversion subsample is 14,187 and the conversion rate was 13.80% (95% confidence interval: 13.54-14.06%) during the 11-year follow-up. The conversion rate was highest in the first year (4.50%; 4.39-4.61%) and decreased over time. The significant predictors were younger age of diagnosis with MDD (p < 0.001), moderate and high antidepressant resistance (p < 0.001), obesity (p < 0.001), psychiatric comorbidities (attention-deficit/hyperactivity disorder, substance use disorder, and cluster B and C personality disorder, all p < 0.001), a family history of mental disorders (schizophrenia and mood disorders, all p < 0.05), lower monthly income (p < 0.001), and more mental health visits to the clinic each year (p < 0.001). A composite of demographic characteristics, antidepressant resistance, physical and psychiatric comorbidities, and family history significantly predicted diagnostic conversion from MDD to BD (area under the curve = 0.795, p < 0.001). Compared to adult population, the adolescents and young adults had different factors that were most or less predictive of conversion, which warrants further investigation., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Consent to participate Informed consent was obtained from all individual participants included in the study. Ethics approval Approval was obtained from the ethics committee of the Taipei Veterans General Hospital. The procedures used in this study adhere to the tenets of the Declaration of Helsinki., (© 2024. The Author(s).)

Purpose: People with severe mental illness (SMI) experience high levels of unemployment. We aimed to better understand the associations between clinical, social, and demographic inequality indicators and unemployment., Methods: Data were extracted from de-identified health records of people with SMI in contact with secondary mental health services in south London, UK. A Natural Language Processing text-mining application was applied to extract information on unemployment in the health records. Multivariable logistic regression was used to assess associations with unemployment, in people with SMI., Results: Records from 19,768 service users were used for analysis, 84.9% (n = 16,778) had experienced unemployment. In fully adjusted models, Black Caribbean and Black African service users were more likely to experience unemployment compared with White British service users (Black Caribbean: aOR 1.62, 95% CI 1.45-1.80; Black African: 1.32, 1.15-1.51). Although men were more likely to have experienced unemployment relative to women in unadjusted models (OR 1.36, 95% CI 1.26-1.47), differences were no longer apparent in the fully adjusted models (aOR 1.05, 95% CI 0.97-1.15). The presence of a non-affective (compared to affective) diagnosis (1.24, 1.13-1.35), comorbid substance use (2.02, 1.76-2.33), previous inpatient admissions (4.18, 3.71-4.70), longer inpatient stays (78 + days: 7.78, 6.34-9.54), and compulsory admissions (3.45, 3.04-3.92) were associated with unemployment, in fully adjusted models., Conclusion: People with SMI experience high levels of unemployment, and we found that unemployment was associated with several clinical and social factors. Interventions to address low employment may need to also address these broader inequalities., (© 2024. The Author(s).)

Importance: Recurrent copy number variants (rCNVs) have been associated with increased risk of psychiatric disorders in case-control studies, but their population-level impact is unknown., Objective: To provide unbiased population-based estimates of prevalence and risk associated with psychiatric disorders for rCNVs and to compare risks across outcomes, rCNV dosage type (deletions or duplications), and locus features., Design, Setting, and Participants: This genetic association study is an analysis of data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) case-cohort sample of individuals born in Denmark in 1981-2008 and followed up until 2015, including (1) all individuals (n = 92 531) with a hospital discharge diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder, major depressive disorder (MDD), or schizophrenia spectrum disorder (SSD) and (2) a subcohort (n = 50 625) randomly drawn from the source population. Data were analyzed from January 2021 to August 2023., Exposures: Carrier status of deletions and duplications at 27 autosomal rCNV loci was determined from neonatal blood samples genotyped on single-nucleotide variant microarrays., Main Outcomes and Measures: Population-based rCNV prevalence was estimated with a survey model using finite population correction to account for oversampling of cases. Hazard ratio (HR) estimates and 95% CIs for psychiatric disorders were derived using weighted Cox proportional hazard models. Risks were compared across outcomes, dosage type, and locus features using generalized estimating equation models., Results: A total of 3547 rCNVs were identified in 64 735 individuals assigned male at birth (53.8%) and 55 512 individuals assigned female at birth (46.2%) whose age at the end of follow-up ranged from 7.0 to 34.7 years (mean, 21.8 years). Most observed increases in rCNV-associated risk for ADHD, ASD, or SSD were moderate, and risk estimates were highly correlated across these disorders. Notable exceptions included high ASD-associated risk observed for Prader-Willi/Angelman syndrome duplications (HR, 20.8; 95% CI, 7.9-55). No rCNV was associated with increased MDD risk. Also, rCNV-associated risk was positively correlated with locus size and gene constraint but not with dosage type. Comparison with published case-control and community-based studies revealed a higher prevalence of deletions and lower associated increase in risk for several rCNVs in iPSYCH2015., Conclusions and Relevance: This study found that several rCNVs were more prevalent and conferred less risk of psychiatric disorders than estimated previously. Most case-control studies overestimate rCNV-associated risk of psychiatric disorders, likely because of selection bias. In an era where genetics is increasingly being clinically applied, these results highlight the importance of population-based risk estimates for genetics-based predictions.

Aims: To study the prevalence of fatigue and factors associated with fatigue in patients with major depressive disorder (MDD) or bipolar disorder (BD)., Methods: Two hundred fifty-three outpatients with MDD or BD at the initial assessment were used to study the prevalence of fatigue and relationship between fatigue and other clinical correlates. The severity of fatigue was measured with Iowa Fatigue Scale (IFS), and depression and anxiety symptom-severity were measured with the QIDS-16-SR (the 16-item Quick Inventory of Depressive Symptomatology - Self-Report) and Zung-SAS (Zung Self-Rating Anxiety Scale). Correlation between IFS and QIDS-16-SR total scores, QIDS-16-SR item scores or Zung-SAS total scores, and independent factors associated with fatigue was assessed with simple or multiple linear regression analysis., Results: Overall, 28.4 % of MDD and 29.8 % of BD patients did not have fatigue, but 41.2 % of MDD and 45.0 % of BD patients had fatigue, and 30.4 % of MDD and 25.2 % of BD patients had severe fatigue. Depression/anxiety severity was significantly correlated with fatigue. However, after controlling current psychiatric comorbidities, demographics, some social factors, and psychotropic use, only QIDS-16-SR scores were still significantly and positively correlated with IFS scores in both MDD and BD. Differential correlations between IFS scores and item scores of QIDS-16-SR in MDD and BD were observed., Limitation: Cross-sectional., Conclusions: In this outpatient sample, fatigue was highly prevalent in patients with MDD or BD. The independent association of depressive severity with the severity of fatigue highlights the importance of complete resolution of depressive symptoms in treating MDD and BD., Competing Interests: Declaration of competing interest Dr. Joseph R. Calabrese received federal funding from the Department of Defense, Health Resources Services Administration and National Institute of Mental Health as well as grant support from: Abbott Laboratories; AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc. (now Teva Pharmaceutical Industries Ltd.); Dainippon Sumitomo Pharma Co., Ltd.; GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Eli Lilly and Company; Intra-Cellular Therapies, Inc.; Pfizer, Inc; H. Lundbeck A/S; Sunovion Pharmaceuticals Inc.; Takeda Pharmaceutical Company Limited. Dr. Calabrese has served as a consultant/advisory board member/speaker for: Abbott Laboratories; Allergan; AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc. (now Teva Pharmaceutical Industries Ltd.); Dainippon Sumitomo Pharma Co., Ltd.; GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; H. Lundbeck A/S,;Merck & Co., Inc.; Otsuka Pharmaceutical Co., Ltd.; Pfizer, Inc.; Repligen Corporation; Servier; Sunovion Pharmaceuticals Inc.; Solvay Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited. Dr. Keming Gao was on a speakers bureau of AstraZeneca, Pfizer and Sunovion, and an advisory board of Sunovion and Otsuka, and received grant supports from AstraZeneca, Brain and Behavior Research Foundation, and Cleveland Foundation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Bipolar disorder (BD) has been reconceptualised as a progressive disorder that develops from mild to severe presentations. An empirical staging model - the Empirically Developed Clinical Staging Model for BD (EmDe-5) - was developed in a previous study. This study aims to further validate that model using a larger and more representative Spanish sample., Material and Methods: 183 BD outpatients were recruited at 11 sites in Spain. Assessment included clinical characteristics of the BD (number of hospitalisations, number of suicide attempts, comorbid personality disorders), physical health (BMI, metabolic syndrome, number of physical illnesses), cognition (SCIP), functioning (permanently disabled due to BD, FAST), and quality of life (SF-36). The CGI-S, VAS-S, and psychopharmacological treatment pattern were used as external validators., Results: Ten patients (51.5%) were classified as stage 1, 33 (18%) as stage 2, 93 (508%) as stage 3, 37 (202%) as stage 4, and 10 (55%) as stage 5. All profilers, other than number of suicide attempts (p=0.311) and comorbid personality disorder (p=0.061), exhibited worse scores from stage 1 to 5. As expected, VAS-S and CGI-S scores were worse in the later stages. Regarding treatment, early stages (1-2) were associated with the use of one to three drugs while late stages (4-5) were associated with four or more drugs (p=0.002)., Conclusions: We confirm the EmDe-5 staging model's construct validity. The ease of obtaining the profilers, together with the operational criteria provided to quantify them, will facilitate the use of the EmDe-5 staging model in daily clinical practice., (Copyright © 2021. Published by Elsevier España S.L.U.)

Background: Offspring of parents with bipolar disorder have increased risks of their own psychopathology. However, a large-scale survey of psychiatric, somatic, and adverse social outcomes up to adulthood, which could aid in prioritizing and tailoring prevention, is lacking. It also remains to clarify how risks are modified by other parental factors., Methods: Swedish population registers were linked to compare offspring having (N = 24,788) and not having (N = 247,880) a parent with bipolar disorder with respect to psychiatric diagnoses and psychotropic medication, birth-related and somatic conditions, social outcomes, accidents, suicide attempts, and mortality. Individuals were followed until age 18. We estimated the influence of lifetime parental psychiatric comorbidity, bipolar disorder subtype, and sex on outcomes., Results: Children of parents with bipolar disorder had 2-3 times higher risks of all psychiatric diagnoses, except for bipolar disorder, for which the risk was 11-fold. Significantly increased risks were also found for several somatic conditions, low school grades, criminal behavior, victimization, accidents, and suicidal behavior. Adjusting for lifetime parental psychiatric comorbidity attenuated most associations. Offspring of a parent with bipolar disorder type 2 had statistically significantly higher risks of attention deficit hyperactivity disorder, respiratory tract conditions, and accidents compared with offspring of a parent with bipolar disorder type 1. Offspring of mothers with bipolar disorder had higher risks of several psychiatric diagnoses, respiratory tract conditions, low school grades, and accidents compared with offspring of fathers with bipolar disorder. Having two parents with bipolar disorder entailed the highest risks of psychiatric outcomes in offspring., Conclusions: Early intervention and family support are particularly warranted for the offspring of a parent with bipolar disorder in the presence of lifetime parental psychiatric comorbidity, when the parent has bipolar disorder type 2, or when the mother or both parents have bipolar disorder., (© 2024 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: The mental health of child and adolescent intensive care unit (ICU) survivors is increasingly being researched. However, the literature on how various types of critical illness influence specific psychiatric disorders remains limited., Methods: This study analyzed the data of 8704 child and adolescent ICU survivors and 87,040 age-, sex-, family income-, and residence-matched controls who were followed from enrollment to the end of 2013; the data covered the period from 1996 to 2013 and were extracted from a nationwide data set. The primary outcomes were the risks of five major psychiatric disorders (MPDs), namely schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD)., Results: Relative to the controls, the child and adolescent ICU survivors (mean age = 10.33 years) exhibited higher risks of developing five MPDs. The associated hazard ratios (HRs) and confidence intervals (CIs) are as follows: PTSD, HR = 4.67, 95 % CI = 2.42-9.01; schizophrenia, HR = 3.19, 95 % CI = 2.27-4.47; BD, HR = 2.02, 95 % CI = 1.33-3.05; OCD, HR = 1.96, 95 % CI = 1.21-3.16; and MDD, HR = 1.68, 95 % CI = 1.44-1.95. The risks of developing MPDs varied across multiple types of critical illness related to ICU admission., Conclusions: The risks of MPDs were significantly higher among the child and adolescent ICU survivors than among the controls. The development of appropriate MPD prevention strategies should be emphasized for this vulnerable population., Competing Interests: Declaration of competing interest All authors declare that No conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Seasonality in depressive and bipolar disorders, are recognized in the ICD-10/11 and DSM-5 diagnostic systems. The existence of a seasonal pattern of hospital diagnosis of major depression, bipolar disorder and prescription of antidepressant medications has not been evaluated in the Danish population., Methods: We retrieved date and year for all first-time hospital contacts with depression or bipolar disorder between 1999 and 2019, registered in the Danish National Patient Registry. Depression was defined using the ICD-10 F32-F33 codes, and for bipolar disorder the F30 or F31 codes. Date and year of all first-time purchases of antidepressant medications with ATC codes (N06A) between 1999 and 2021 were retrieved from the Danish National Prescription Registry, containing information on all prescribed drugs dispensed at pharmacies since 1995. Data on sunlight hours from 2012 to 2021 were retrieved from the Danish Metrological Institute., Results: Incidences of hospital diagnoses as well as purchases of medication varied with month and season. The monthly variations were larger for antidepressant medication and smallest for bipolar disorder. The multiple linear regression analysis showed that number of first-time diagnoses of depression or bipolar disorder did not correlate with season. For antidepressant medication the number of first-time prescriptions was significantly lower in summer compared to the winter season., Conclusion: This study found a seasonal variation of first-time prescriptions of antidepressant medication. We did not find a seasonal variation in first-time hospital diagnoses. Further research looking into depression severity, polarity of bipolar illness episodes, lag-time for sunlight exposure, and specific parts of the yearly photoperiods should be conducted.

Background: Perinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and 'high-risk' for BD in the general population., Methods: Parent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as 'high-risk' for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample., Results: Prenatal alcohol exposure (β = 0.08, SE = 0.04, p = .0002) and number of alcohol units consumed (β = 0.09, SE = 0.02, p < .0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06-1.21, p = .0003) and maternal stress (OR = 1.68, 95 % CI:1.21-2.34, p = .002) were associated with 'high-risk' for BD age 16. Prenatal tobacco exposure (β = 0.10, SE = 0.04, p < .0001) and number of cigarettes smoked (β = 0.10, SE = 0.01, p < .0001) were associated with hypomanic symptoms and 'high-risk' for BD at age 26, although these result were attenuated controlling for parental psychiatric history., Limitations: Familial confounding could not be fully adjusted for. Rater reports include some biases., Conclusions: These findings show perinatal risk factors to be associated with subclinical hypomania and 'high-risk' for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Female infertility is a global issue that impacts on public health seriously and many mental disorders are observed in infertility groups., Methods: To investigate the casual relationship between those, genome-wide association studies summary data of anxiety disorder (n=9,897), broad depression (n=322,580), major depressive disorder (n=480,359 and n=500,199), bipolar disorder (n=51,710), insomnia (n= 462,341), and female infertility (n=126,342) were extracted from the existing datasets and was analyzed through the two-sample mendelian randomization study. The following heterogeneity and sensitivity test were applied to ensure the robustness of results., Results: Based on inverse variance weighted results, major depressive disorder was associated with female infertility (P = 0.0001, odds ratio 1.396, 95 % confidence interval 1.175-1.658). No causal relationship was identified between the other four mental disorders and infertility. was found. Additionally, reverse mendelian randomization did not indicate a causal relationship among these disorders., Discussion: The early identification and management of anxiety symptoms in women of reproductive age, in conjunction with the effective treatment of major depressive disorder, may be crucial for preserving female fertility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mao, Lin and Li.)

Background: Major depressive disorder (MDD) is a leading cause of disability and premature mortality. This study compared the overall survival (OS) between patients with MDD and non-MDD controls stratified by gender, age, and comorbidities., Methods: This nationwide population-based cohort study utilized longitudinal patient data (01/01/2010 - 12/31/2020) from the Hungarian National Health Insurance Fund database, which contains healthcare service data for the Hungarian population. Patients with MDD were selected and matched 1:1 to those without MDD using exact matching. The rates of conversion from MDD to bipolar disorder (BD) or schizophrenia were also investigated., Results: Overall, 471,773 patients were included in each of the matched MDD and non-MDD groups. Patients with MDD had significantly worse OS than non-MDD controls (hazard ratio [HR] = 1.50; 95% CI: 1.48-1.51; males HR = 1.69, 95% CI: 1.66-1.72; females HR = 1.40, 95% CI: 1.38-1.42). The estimated life expectancy of patients with MDD was 7.8 and 6.0 years less than that of controls aged 20 and 45 years, respectively. Adjusted analyses based on the presence of baseline comorbidities also showed that patients with MDD had worse survival than non-MDD controls (adjusted HR = 1.29, 95% CI: 1.28-1.31). After 11 years of follow-up, the cumulative conversions from MDD to BD and schizophrenia were 6.8 and 3.4%, respectively. Converted patients had significantly worse OS than non-converted patients., Conclusions: Compared with the non-MDD controls, a higher mortality rate in patients with MDD, especially in those with comorbidities and/or who have converted to BD or schizophrenia, suggests that early detection and personalized treatment of MDD may reduce the mortality in patients diagnosed with MDD.

Background: Childhood maltreatment (CM) is prevalent among patients with mood disorders and considered an important risk factor for suicide in the general population. Despite mood disorders being implicated in up to 60 % of completed suicides, the predictive role of CM on suicide attempt (SA) among early mood disorder patients remains poorly understood., Methods: We enrolled 480 participants diagnosed with early-onset major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II). Over an average of 60 weeks, participants underwent follow-up assessments at 12-week intervals. Using multivariate logistic regression, we examined the association between CM and SA history at baseline. Further, the Cox proportional hazard model assessed the predictive role of childhood maltreatment in SA during follow-up., Results: At baseline, 38 % of the total participants reported SA history, with a follow-up prevalence of 10 %. Childhood maltreatment was significantly associated with past SAs and was a robust predictor of future SA, adjusting for relevant clinical risk factors. Emotional abuse and sexual abuse related to SA history, and physical abuse increased future SA risk., Limitations: Potential biases in reporting SA and childhood maltreatment, along with unexplored factors such as additional environmental and familial risks, may affect the study's findings., Conclusions: Childhood maltreatment emerged as a robust predictor of SA among early-onset mood disorder patients. Systematic evaluation of CM early in the clinical process may be crucial for effective risk management. Additionally, our findings highlight the importance of implementing proactive interventions for CM to prevent the onset of adverse psychological trajectories., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Depersonalization/derealization disorder (DPD) is a prevalent yet inadequately understood clinical condition characterized by a recurrent or persistent sense of unreality. This study aims to provide insight into DPD through descriptive and comparative analyses involving a large group of Chinese participants. The socio-demographic details (age, gender proportion, education, occupational status, marital status), depersonalized and dissociative symptom characteristics (symptomatic factors or subscales of the Cambridge Depersonalization Scale and the Dissociative Experiences Scale), development trajectory (age of onset, potential precipitating factors, course characteristics), treatment history (duration of delayed healthcare attendance, duration of delayed diagnosis, previous diagnoses), and adverse childhood experiences of the DPD patients are presented. Comparisons of anxiety and depressive symptoms, alongside psychosocial functioning, between DPD participants and those diagnosed with generalized anxiety disorder, bipolar disorders, and major depressive disorder were conducted. The analysis highlights a higher male preponderance and early onset of DPD, symptomatology marked by derealization, notable impairment in psychosocial functioning, and prolonged periods of delayed healthcare attendance and diagnosis associated with symptom severity. Furthermore, noteworthy relationships between adverse childhood experiences and symptom levels were identified. The findings substantiate the view that DPD is a serious but neglected mental disorder, urging initiatives to improve the current condition of DPD patients., (© 2024. The Author(s).)

Objective: To identify factors associated with receiving electroconvulsive therapy (ECT) for serious psychiatric conditions., Methods: Retrospective observational study using hospital administrative data linked with death registrations and outpatient mental health data in New South Wales (NSW), Australia. The cohort included patients admitted with a primary psychiatric diagnosis between 2013 and 2022. The outcome measure was receipt of ECT., Results: Of 94,950 patients, 3465 (3.6%) received ECT. The likelihood of receiving ECT was higher in older (hazard ratio [HR] = 1.03), female (HR = 1.24) patients. Compared to depression, patients with schizophrenia/schizoaffective disorder (HR = 0.79), schizophrenia-related disorders (HR = 0.37), mania (HR = 0.64) and other mood disorders (HR = 0.45) had lower odds of receiving ECT. Patients with depression and one other serious psychiatric condition had higher odds of receiving ECT than depression alone. Bipolar disorder likelihood of ECT did not differ from depression. A higher number of mental health outpatient visits in the prior year and an involuntary index admission with depression were also associated with receiving ECT. Likelihood of receiving ECT increased with year of admission (HR = 1.32), private patient status (HR = 2.06), higher socioeconomic status (HR = 1.09) and being married (HR = 1.25)., Conclusions: ECT use for depression and bipolar disorder in NSW aligns with clinical national guidelines. Patients with schizophrenia/schizoaffective, schizophrenia-related disorders, mania and other mood disorders had lower likelihood of ECT than depression, despite ECT being recommended by clinical guidelines for these diagnoses. Variations in ECT were strongly associated with healthcare access, with private patients twice as likely to receive ECT than their public counterparts, suggesting a need to explore ECT accessibility., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: Some studies and societal discussions have suggested a potential link between overweight and a higher risk of mental disorders and suicidal ideation. However, the causal relationships between these factors remain unclear. This study aims to assess the bidirectional causal associations between overweight and mental disorders, including suicidal attempts., Method: We conducted a Two-Sample Mendelian Randomization study utilizing data from over 450,000 individuals of European ancestry sourced from a comprehensive Genome-Wide Association Study database. We chose single-nucleotide polymorphisms as instrumental variables., Results: Our analyses consistently supported a unidirectional causal association of overweight with the increased risk of major depressive disorder (MDD, β = 0.152, se = 0.069, P = 0.027), bipolar affective disorders (BD, β = 0.197, se = 0.092, P = 0.033), and attention-deficit / hyperactivity disorder (ADHD, β = 0.308, se = 0.080, P = 1.366 × 10 -4 ). We observed no significant causal relationships for the exposure of overweight to anxiety disorder (AD), manic episode (MA), panic disorder (PD), schizophrenia (SZ), substance use disorder (SUD), autism spectrum disorder (ASD), ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events., Conclusion: This study has provided evidence for the causal relationship between overweight and MDD, BD, ADHD, with no observed relationship between overweight and AD, MA, PD, SZ, SUD, ASD, ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events., Competing Interests: Declaration of competing interest The authors declare no financial interests or potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44-0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures., Competing Interests: Declaration of competing interest Esther W. Chan has received grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Novartis, Amgen, AstraZeneca, Takeda, the RGA Reinsurance Company, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, the National Health and Medical Research Council Australia; consulting fees from AstraZeneca, Pfizer and Novartis; and honorarium from the Hospital Authority Hong Kong, outside the submitted work. Joseph F. Hayes has received consultancy fees from Wellcome Trust and juli Health. Kenneth K.C. Man received the CW Maplethorpe Fellowship, grants from the National Institute for Health Research (United Kingdom), the European Union Horizon 2020 Framework, Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and Hong Kong Research Grant Council and personal fees from IQVIA Holdings, Inc., unrelated to this work. Ian C.K.Wong received research grants from Amgen, Janssen, GSK, Novartis, Pfizer, Bayer and Bristol-Myers Squibb and Takeda, Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, The European Union's Seventh Framework Programme for research, technological development, Research Grants Council Hong Kong and Health and Medical Research Fund Hong Kong; consulting fee from IQVIA and WHO; payment for expert testimony for Appeal Court in Hong Kong; serves on advisory committees for Member of Pharmacy and Poisons Board; Member of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization; Member of the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government; is the non-executive director of Jacobson Medical in Hong Kong; is the Founder and Director of Therakind Limited (UK), Advance Data Analytics for Medical Science (ADAMS) Limited (HK), Asia Medicine Regulatory Affairs (AMERA) Services Limited and OCUS Innovation Limited (HK, Ireland and UK). Ching-Lung Cheung received research grants and the honorarium from Amgen, research grant support from HMRF, and the honorarium from Abbott. Wallis C.Y. Lau reports grant from Diabetes UK, AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. Vanessa W.S. Ng, Miriam T.Y. Leung, and David P.J. Osborn declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Individuals with bipolar disorders (BD) have heterogenic pre-onset illness courses and responses to treatment. The pattern of illness preceding the diagnosis of BD may be a marker of future treatment response. Here, we examined associations between psychiatric morbidity preceding the diagnosis of BD and pharmacological treatment patterns in the 2 years following diagnosis., Methods: In this register-based study, we included all patients with a diagnosis of BD attending Danish Psychiatric Services between January 1, 2012 and December 31, 2016. We examined the association between a diagnosis of substance use disorder, psychosis (other than schizophrenia or schizoaffective disorder), unipolar depression, anxiety/OCD, PTSD, personality disorder, or ADHD preceding BD and pharmacological treatment patterns following the diagnosis of BD (lithium, valproate, lamotrigine, antidepressants, olanzapine, risperidone, and quetiapine) via multivariable Cox proportional hazards regression adjusted for age, sex, and year of BD diagnosis., Results: We included 9594 patients with a median age of 39 years, 58% of whom were female. Antidepressants, quetiapine, and lamotrigine were the most commonly used medications in BD and were all linked to prior depressive illness and female sex. Lithium was used among patients with less diagnostic heterogeneity preceding BD, while valproate was more likely to be used for patients with prior substance use disorder or ADHD., Conclusion: The pharmacological treatment of BD is linked to psychiatric morbidity preceding its diagnosis. Assuming that these associations reflect well-informed clinical decisions, this knowledge may inform future clinical trials by taking participants' prior morbidity into account in treatment allocation., (© 2024 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Aim: Bipolar disorder (BD) and borderline personality disorder (BPD) are both serious psychiatric conditions that elevate the risk for harmful outcomes. Although these conditions represent distinct diagnostic entities, existing research suggests that approximately 20% of individuals with BD meet the criteria for comorbid BPD. Individuals with comorbid BD/BPD appear to have a markedly more severe and phenomenologically distinct clinical course when compared with those with BD alone. However, treatments have generally not been tested in this specific population, and currently, no formal treatment guidelines exist for this subgroup of patients., Method: In the current paper, we review the epidemiological and descriptive research characterizing those with comorbid BD/BPD and discuss the impact of this comorbidity on psychosocial treatment. We also review current findings on evidence-based treatments for BD and BPD that show promise in treating those with comorbid BD/BPD., Results: In our review of the literature, we highlight the importance of recognizing this comorbidity and discuss avenues for developing and integrating evidence-based treatment approaches for this understudied clinical population., Conclusions: Although formal trials of interventions targeted to comorbid BD/BPD are limited, there is promising evidence regarding the possibility of using or integrating existing evidence-based approaches for this population. There are also several areas of clinical practice improvement and future research directions that stem from this literature., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although several meta-analyses have examined the association between bipolar disorder (BD) and its comorbid health outcomes, this evidence has not been comprehensively assembled., Objective: We aimed to systematically review existing meta-analyses based on multiple physical outcomes and validate the evidence level by examining the existing certainty of evidence., Methods: We systematically searched databases, including PubMed/MEDLINE, Embase, Google Scholar, and CINAHL, for articles published up to July 2023. We included meta-analyses of cohort, case-control, and/or cross-sectional studies investigating any comorbid health outcomes in patients with BD. We conducted quality assessments of the included meta-analysis using AMSTAR2. The credibility of findings was categorized into five levels of class and quality of evidence (CE), including convincing, highly suggestive, suggestive, weak, or not significant., Results: We analyzed 12 meta-analyses, including 145 original articles, covering 14 unique health outcomes with over 60 million participants across 29 countries and five continents. Among 14 health outcomes, BD was significantly associated with eight comorbid health outcomes, including dementia (equivalent odds ratio [eOR], 2.96 [95 % confidence intervals {CI}, 1.69-5.17]; CE=suggestive), Parkinson's disease (3.35 [1.72-6.53]; CE=suggestive), asthma (1.86 [1.42-2.42]; CE=weak), toxoplasmosis (1.69 [1.21-2.37]; CE=weak), hypertension (1.28 [1.02-1.60]; CE=convincing), breast cancer (1.33 [1.15-1.55]; CE=weak), obesity (1.64 [1.30-1.99]; CE=suggestive), and type 2 diabetes mellitus (1.98 [1.55-2.52]; CE=weak)., Conclusion: Individuals with BD are predisposed to numerous comorbid physical conditions, though these links are supported by various evidence levels and necessitate further studies. It is imperative that physicians be aware of these potential comorbidities in patients with BD and take proactive measures to manage them., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The diagnostic criteria of bipolar disorder (BD) have changed over time. To test if these changes are reflected in the polygenic profile in BD, we studied the association between first BD diagnosis year (during 1972-2016) and polygenic scores (PGS) for psychiatric disorders in BD patients (N = 3,818). We found significant associations between diagnosis year and PGS for BD, depression, and attention deficit hyperactivity disorder (ADHD). The PGS remained largely stable over time in BD type 1, while changes were observed in BD type 2. These findings bear significance not only for genetic research but also for clinical practise, as shifts in patient characteristics can influence treatment response., Competing Interests: Declaration of competing interest ML declares that he has received lecture honoraria from Lundbeck pharmaceutical outside the scope of this work. EJ is currently employed at IQVIA, Mölndal, Sweden., (Copyright © 2024. Published by Elsevier B.V.)

Previous research examining bipolar-disorder (BD) and pregnancy/neonatal outcomes yielded mixed results, were mostly derived from Western countries and rarely delineated effect between disorder and mood-stabilizers. This population-based study identified women age 15-50 years who delivered first/singleton child in 2003-2018 in Hong Kong, utilizing territory-wide medical-record database of public healthcare services. Propensity-score weighted logistic-regression analyses adjusted for confounders were employed to examine risk of adverse pregnancy, delivery and neonatal outcomes associated with BD and mood-stabilizers (lithium, anticonvulsants and antipsychotics). Exploratory unadjusted-analyses were conducted to assess risk for congenital-malformations. Of 465,069 women, 302 had BD-diagnosis, including 168 redeemed ≥ 1 prescription of mood-stabilizers during pregnancy (treated-BD) and 134 gestationally-unexposed to mood-stabilizers (untreated-BD). BD was significantly-associated with increased risk of gestational-diabetes (adjusted-odds-ratio: 1.75 [95 % CI: 1.15-2.70]) and maternal somatic hospitalization ≤ 90 days post-discharge from index-delivery (2.12 [1.19-3.90]). In treatment status-stratified analyses, treated-BD women exhibited significantly-increased rate of gestational-diabetes (2.09 [1.21-3.70]) relative to controls (non-BD and gestationally-unexposed to mood-stabilizers). No significant association of BD or mood-stabilizers with other adverse outcomes was observed. Overall, our findings indicate that BD and mood-stabilizers are not associated with most adverse pregnancy, delivery and neonatal outcomes. Further research clarifying comparative safety of individual mood-stabilizing agents on pregnancy/neonatal outcomes is required., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder often emerges from depressive episodes and is initially diagnosed as depression. This study aimed to explore the effects of a prior depression diagnosis on outcomes in patients diagnosed with bipolar disorder., Methods: This cohort study analyzed data of patients aged 18-64 years who received a new bipolar disorder diagnosis in Japan, using medical claims data from January 2005 to October 2020 provided by JMDC, Inc. The index month was defined as the time of the bipolar diagnosis. The study assessed the incidence of psychiatric hospitalization, all-cause hospitalization, and mortality, stratified by the presence of a preceding depression diagnosis and its duration (≥1 or <1 year). Hazard ratios (HRs) and p-values were estimated using Cox proportional hazards models, adjusted for potential confounders, and supported by log-rank tests., Results: Of the 5595 patients analyzed, 2460 had a history of depression, with 1049 experiencing it for over a year and 1411 for less than a year. HRs for psychiatric hospitalization, all hospitalizations, and death in patients with a history of depression versus those without were 0.92 (95% CI = 0.78-1.08, p = 0.30), 0.87 (95% CI = 0.78-0.98, p = 0.017), and 0.61 (95% CI = 0.33-1.12, p = 0.11), respectively. In patients with preceding depression ≥1 year versus <1 year, HRs were 0.89 (95% CI = 0.67-1.19, p = 0.43) for psychiatric hospitalization, 0.85 (95% CI = 0.71-1.00, p = 0.052) for all hospitalizations, and 0.25 (95% CI = 0.07-0.89, p = 0.03) for death., Conclusion: A prior history and duration of depression may not elevate psychiatric hospitalization risk after bipolar disorder diagnosis and might even correlate with reduced hospitalization and mortality rates., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Objectives: To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence., Methods: OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women)., Results: After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38-3.30]), renal (5.97 [1.31-43.16]), musculoskeletal (2.09 [1.30-3.43]) and endocrine (1.90 [1.20-3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99-2.49]), genitourinary (1.72 [1.02-2.92]), musculoskeletal (2.64 [1.66-4.37]) and endocrine (1.71 [1.08-2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled., Conclusions: This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women., Competing Interests: Declaration of competing interest VB-M has received honoraria from Angelini, unrelated to the present work. JBL has received grant funding from NIH, AHA, and Merck. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Bipolar disorder (BD) often first appears in adolescence after onset of major depressive disorder (MDD), but diagnosis and treatment are commonly delayed. This delay is a concern because untreated BD is associated with adverse long-term outcomes, a more recurrent disease course and difficult-to-treat illness, and suicide attempts and deaths., Objective: To examine the association of age at MDD onset with early transition to BD and the subsequent use of psychiatric inpatient services as a severity indicator., Design, Setting, and Participants: This retrospective cohort study analyzed comprehensive data sourced from the Stockholm MDD Cohort data from 1997 to 2018, which encompass both outpatient and inpatient care. Individuals with an initial MDD episode from January 1, 2010, to December 31, 2013, who transitioned to BD by December 31, 2018, were identified. Data were analyzed between September 5 and December 28, 2023., Exposures: Post MDD assessments included a depression severity index, comorbidities, psychotherapy, psychotropic drugs, and electroconvulsive therapy., Main Outcomes and Measures: The main outcome was the transition from MDD to BD, dichotomized as occurring early (within 3 years of MDD onset) or late (3 years after MDD onset). Secondary outcomes encompassed the use of psychiatric inpatient services post transition and patterns of medication usage. A robust propensity score matching framework was used to estimate outcomes., Results: The final balanced cohort included 228 individuals, with an equal distribution between adults (n = 114; mean [SD] age, 24.5 [6.3] years; 96 female [84.2%]; 20 experiencing an early transition to BD [17.5%]) and youths (n = 114; mean [SD] age, 15.3 [1.6] years; 93 female [81.6%]; 8 experiencing an early transition to BD [7.0%]). Youths were substantially less likely to transition early (odds ratio, 0.42; 95% CI, 0.20-0.88; P = .02), despite having more outpatient visits (mean [SD] visits per month, 1.21 [1.07] vs 0.97 [0.98] for adults; P = .01). Both groups experienced substantially reduced inpatient care following a BD diagnosis, concurring with a marked decline in antidepressant use without increased lithium use., Conclusions and Relevance: These findings suggest that adolescents may experience delayed BD progression and that diagnosis substantially reduced inpatient care in all age groups, which coincided with a reduction in the use of antidepressants. These findings may inform pharmacologic strategies in patients with first-episode MDD at risk for BD.

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The association between mood disorders, especially bipolar disorder (BD), and metabolic disorders, is long known. However, to which extent metabolic disorders affect the course of mood disorders in late life is still open to inquiring. To assess the impact of type 2 diabetes mellitus (T2DM) on late-life mood disorders a retrospective chart review was performed. Elderly depressive patients (≥ 65 years) diagnosed with Major Depressive Disorder (N = 57) or BD (N = 43) and followed up for at least 18 months were included and subdivided according to the presence of T2DM comorbidity. Vascular encephalopathy (39.1% vs. 15.6%, P  = 0.021) and neurocognitive disorders (21.7% vs. 5.2%, P  = 0.028), were more frequently reported in patients with T2DM than in those without. Patients with T2DM showed a greater percentage of follow-up time in manic episodes (r = -0.23, P  = 0.020) and a higher rate of manic episode(s) during follow-up (21.7% vs. 5.2%, P  = 0.028) than those without. When restricting longitudinal analyses to patients with bipolar spectrum disorders, results were confirmed. In line with the well-known connection between BD and metabolic disorders, our data support an association between T2DM and unfavorable course of illness in the elderly with BD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Observational studies suggest that major psychiatric disorders and substance use behaviors reduce longevity, making it difficult to disentangle their relationships with aging-related outcomes., Objective: To evaluate the associations between the genetic liabilities for major psychiatric disorders, substance use behaviors (smoking and alcohol consumption), and longevity., Design, Settings, and Participants: This 2-sample mendelian randomization (MR) study assessed associations between psychiatric disorders, substance use behaviors, and longevity using single-variable and multivariable models. Multiomics analyses were performed elucidating transcriptomic underpinnings of the MR associations and identifying potential proteomic therapeutic targets. This study sourced summary-level genome-wide association study (GWAS) data, gene expression, and proteomic data from cohorts of European ancestry. Analyses were performed from May 2022 to November 2023., Exposures: Genetic susceptibility for major depression (n = 500 199), bipolar disorder (n = 413 466), schizophrenia (n = 127 906), problematic alcohol use (n = 435 563), weekly alcohol consumption (n = 666 978), and lifetime smoking index (n = 462 690)., Main Outcomes and Measures: The main outcome encompassed aspects of health span, lifespan, and exceptional longevity. Additional outcomes were epigenetic age acceleration (EAA) clocks., Results: Findings from multivariable MR models simultaneously assessing psychiatric disorders and substance use behaviorsm suggest a negative association between smoking and longevity in cohorts of European ancestry (n = 709 709; 431 503 [60.8%] female; β, -0.33; 95% CI, -0.38 to -0.28; P = 4.59 × 10-34) and with increased EAA (n = 34 449; 18 017 [52.3%] female; eg, PhenoAge: β, 1.76; 95% CI, 0.72 to 2.79; P = 8.83 × 10-4). Transcriptomic imputation and colocalization identified 249 genes associated with smoking, including 36 novel genes not captured by the original smoking GWAS. Enriched pathways included chromatin remodeling and telomere assembly and maintenance. The transcriptome-wide signature of smoking was inversely associated with longevity, and estimates of individual smoking-associated genes, eg, XRCC3 and PRMT6, aligned with the smoking-longevity MR analyses, suggesting underlying transcriptomic mediators. Cis-instrument MR prioritized brain proteins associated with smoking behavior, including LY6H (β, 0.02; 95% CI, 0.01 to 0.03; P = 2.37 × 10-6) and RIT2 (β, 0.02; 95% CI, 0.01 to 0.03; P = 1.05 × 10-5), which had favorable adverse-effect profiles across 367 traits evaluated in phenome-wide MR., Conclusions: The findings suggest that the genetic liability of smoking, but not of psychiatric disorders, is associated with longevity. Transcriptomic associations offer insights into smoking-related pathways, and identified proteomic targets may inform therapeutic development for smoking cessation strategies.

Background: Anxiety disorder, depression, and bipolar disorder are common psychiatric disorders, and their association with autoimmune thyroiditis (AIT) has been of great interest. This study aimed to investigate the potential causal relationship between these psychiatric disorders and AIT., Methods: We used publicly available summary statistics from large-scale genome-wide association studies to select, quality control and cluster genetic variant loci associated with anxiety disorder, depression, bipolar disorder and AIT as instrumental variables (IVs). The Mendelian randomization (MR) study mainly used inverse variance weighting (IVW) combined with MR-egger regression and weighted median estimation (WME) to estimate bidirectional causality between mental disorders and AIT. In addition, we conducted heterogeneity and multivariate tests to verify the validity of IVW., Results: Two-sample bidirectional MR analysis revealed a positive causal link between depression and AIT. The forward MR analysis of IVW (OR 1.614, 95 % CI 1.104-2.358, P = 0.013) and WME (OR 2.314, 95 % CI 1.315-4.074, P = 0.004) demonstrated thatdepression potentially elevate the risk of AIT development, while, our investigation did not uncover a causal relationship between anxiety disorder, bipolar disorder and AIT. The results of reverse MR analysis showed that there was no significant causal relationship between AIT and anxiety disorder, depression, and bipolar disorder (P > 0.05)., Conclusions: The results of the forward MR analysis suggest a positive association between depression, and AIT risk, while indicating no support for a causal link between anxiety disorder or bipolar disorder and AIT risk based on the current data. Subsequent studies will be essential for elucidating the biological mechanisms and potential confounders underlying these associations., Competing Interests: Declaration of competing interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Obesity is a major concern in patients with bipolar disorder (BD) and problematic eating behaviors have been suggested to mediate their relationship. The association between problematic eating behaviors and obesity has been studied but limited data have explored the role of BD. We investigated problematic eating behaviors among patients with BD compared with candidates for bariatric surgery (BS), with or without BD, and explored the possible correlations between mood spectrum, impulsivity, body mass index (BMI)., Methods: 50 euthymic patients with BD and 200 subjects eligible for BS, 48 with BD (BS + BD) and 152 without BD (BS-BD), were recruited at the Psychiatric Clinic of University of Pisa. Assessments included: Structured Clinical Interview (SCID-5), Emotional Eating Scale (EES), Yale Food Addiction Scale (YFAS), Eating Disorder Inventory (EDI-2), Eating Disorder Questionnaire (EDE-Q), Night Eating Scale (NES), Grazing Questionnaire (GQ), Mood Spectrum Self-Report (MOOD-SR), Barratt Impulsivity Scale (BIS)., Results: BS + BD reported significantly higher EDI-2 and EDE-Q scores than the other groups. BD and BS + BD showed significantly higher BIS-11 scores than BS-BD. Among BS, EES and YFAS were associated with mood spectrum symptoms., Limitations: Small BD sample size, BS may have underreported psychiatric symptoms to get approved for surgery, the interview didn't inquire about BS receiving GLP-1 agonists therapy., Conclusions: Results showed a high prevalence of problematic eating behaviors among patients with BD and severely obese. Problematic eating behaviors may aggravate BD symptoms. Mood spectrum symptoms in obese subjects need to be carefully researched in as relate to severity and post-surgical course of BS., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest relevant to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Anxiety disorders, major psychiatric disorders (e.g., schizophrenia and major affective disorders), and neurodevelopmental disorders (e.g., autism and attention-deficit/hyperactivity disorder [ADHD]) may cluster together within families. However, whether the first-degree relatives (FDRs) of individuals with generalized anxiety disorder (GAD) are at an elevated risk of neurodevelopmental or major psychiatric disorders remains unknown., Methods: We identified 2,378,190 FDRs of patients with GAD and 9,512,760 birth year-matched and sex-matched controls from Taiwan's National Health Insurance Research Database. Neurodevelopmental disorders, including autism and ADHD, and major psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, and GAD, were identified., Results: The FDRs-parents, offspring, and siblings-of individuals with GAD were more likely to be diagnosed as having schizophrenia (relative risk: 1.22), bipolar disorder (1.36), major depressive disorder (1.29), autism (1.20), ADHD (1.52), obsessive-compulsive disorder (1.21), and GAD (1.61) than are the FDRs of individuals without GAD., Conclusion: Our findings support the notion of a familial coaggregation between GAD, major psychiatric disorders, and neurodevelopmental disorders. Future studies should elucidate the definitive genetic etiology of this familial coaggregation., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)