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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: Recent studies have indicated that clinical high risk for psychosis (CHR-P) is highly specific for psychotic disorders other than pluripotential to various serious mental illnesses. However, not all CHR-P develop psychotic disorder only, and psychosis can occur in non-psychotic disorders as well. Our prospective cohort study aims to investigate the characteristics and clinical outcomes of a pluripotent high-risk group with the potential to develop a diverse range of psychiatric disorders., Methods: The SPRIM study is a prospective naturalistic cohort program that focuses on the early detection of those at risk of developing serious mental illness, including psychosis (CHR-P), bipolar (CHR-B), and depressive disorder (CHR-D), as well as undifferentiated risk participants (UCHR). Our study has a longitudinal design with a baseline assessment and eight follow-up evaluations at 6, 12, 18, 24, 30, 36, 42, and 48 months to determine whether participants have transitioned to psychosis or mood disorders., Results: The SPRIM sample consisted of 90 CHR participants. The total cumulative incidence rate of transition was 53.3% (95% CI 32.5-77.2). CHR-P, CHR-B, CHR-D, and UCHR had cumulative incidence rates of 13.7% (95% CI 3.4-46.4), 52.4% (95% CI 28.1-81.1), 66.7% (95% CI 24.6-98.6) and 54.3% (95% CI 20.5-93.1), respectively. The cumulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3% (95% CI 0.8-11.5), 45.7% (95% CI 24.4-73.6), and 11.2% (95% CI 3.1-36.2), respectively., Conclusions: Our study suggests that the concept of pluripotent high-risk for a diverse range of psychiatric disorders is an integrative approach to examining transdiagnostic interactions between illnesses with a high transition rate and minimizing stigma., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The effectiveness of universal preventive approaches in reducing the incidence of affective/psychotic disorders is unclear. We therefore aimed to synthesise the available evidence from randomised controlled trials. For studies reporting change in prevalence, we simulated all possible scenarios for the proportion of individuals with the disorder at baseline and at follow-up to exclude them. We then combined these data with studies directly measuring incidence and conducted random effects meta-analysis with relative risk (RR) to estimate the incidence in the intervention group compared to the control group. Eighteen studies (k=21 samples) were included investigating the universal prevention of depression in 66,625 individuals. No studies were available investigating universal prevention on the incidence of bipolar/psychotic disorders. 63 % of simulated scenarios showed a significant preventive effect on reducing the incidence of depression (k=9 - 19, RR=0.75-0.94, 95 %CIs=0.55-0.87,0.93-1.15, p=0.007-0.246) but did not survive sensitivity analyses. There is some limited evidence for the effectiveness of universal interventions for reducing the incidence of depression but not for bipolar/psychotic disorders., Competing Interests: Declaration of Competing Interest GSP has received honoraria from Lundbeck, Menraini and Janssen Cilag outside of the current study. PFP has received research fees from Lundbeck and received honoraria from Lundbeck, Angelini, Menarini and Boehringer Ingelheim outside of the current study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Major depressive, bipolar, or psychotic disorders are preceded by earlier manifestations in behaviours and experiences. We present a synthesis of evidence on associations between person-level antecedents (behaviour, performance, psychopathology) in childhood, adolescence, or early adulthood and later onsets of major depressive disorder, bipolar disorder, or psychotic disorder based on prospective studies published up to September 16, 2022. We screened 11,342 records, identified 460 eligible publications, and extracted 570 risk ratios quantifying the relationships between 52 antecedents and onsets in 198 unique samples with prospective follow-up of 122,766 individuals from a mean age of 12.4 to a mean age of 24.8 for 1522,426 person years of follow-up. We completed meta-analyses of 12 antecedents with adequate data. Psychotic symptoms, depressive symptoms, anxiety, disruptive behaviors, affective lability, and sleep problems were transdiagnostic antecedents associated with onsets of depressive, bipolar, and psychotic disorders. Attention-deficit/hyperactivity and hypomanic symptoms specifically predicted bipolar disorder. While transdiagnostic and diagnosis-specific antecedents inform targeted prevention and help understand pathogenic mechanisms, extensive gaps in evidence indicate potential for improving early risk identification., Competing Interests: Declaration of Competing Interest RU, BP, SN, NA, BR, EHW, KF, RP, and L. Propper declare no conflict of interest. L. Palaniyappan reports personal fees for serving as chief editor from the Canadian Medical Association Journals, speaker/consultant fees from Janssen Canada and Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Refugees are at increased risk of non-affective psychotic disorders, but it is unclear whether this extends to affective psychotic disorders [APD] or non-psychotic bipolar disorder [NPB]., Methods: We conducted a nationwide cohort study in Sweden of all refugees, non-refugee migrants and the Swedish-born population, born 1 Jan 1984-31 Dec 2016. We followed participants from age 14 years until first ICD-10 diagnosis of APD or NPB. We fitted Cox proportional hazards models to estimate hazard ratios [HR] and 95 % confidence intervals [95%CI], adjusted for age, sex and family income. Models were additionally stratified by region-of-origin., Results: We followed 1.3 million people for 15.1 million person-years, including 2428 new APD cases (rate: 16.0 per 100,000 person-years; 95%CI: 15.4-16.7) and 9425 NPB cases (rate: 63.8; 95%CI: 62.6-65.1). Rates of APD were higher in refugee (HR adjusted : 2.07; 95%CI: 1.55-2.78) and non-refugee migrants (HR adjusted : 1.40; 95%CI: 1.16-1.68), but lower for NPBs for refugee (HR adjusted : 0.24; 95%CI: 0.16-0.38) and non-refugee migrants (HR adjusted : 0.34; 95%CI: 0.28-0.41), compared with the Swedish-born. APD rates were elevated for both migrant groups from Asia and sub-Saharan Africa, but not other regions. Migrant groups from all regions-of-origin experienced lower rates of NPB., Limitations: Income may have been on the causal pathway making adjustment inappropriate., Conclusions: Refugees experience elevated rates of APD compared with Swedish-born and non-refugee migrants, but lower rates of NPB. This specificity of excess risk warrants clinical and public health investment in appropriate psychosis care for these vulnerable populations., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: People with severe mental illness (SMI) face a higher risk of premature mortality due to physical morbidity compared to the general population. Establishing regular contact with a general practitioner (GP) can mitigate this risk, yet barriers to healthcare access persist. Population initiatives to overcome these barriers require efficient identification of those persons in need., Objective: To develop a predictive model to identify persons with SMI not attending a GP regularly., Method: For individuals with psychotic disorder, bipolar disorder, or severe depression between 2011 and 2016 (n = 48,804), GP contacts from 2016 to 2018 were retrieved. Two logistic regression models using demographic and clinical data from Danish national registers predicted severe mental illness without GP contact. Model 1 retained significant main effect variables, while Model 2 included significant bivariate interactions. Goodness-of-fit and discriminating ability were evaluated using Hosmer-Lemeshow (HL) test and area under the receiver operating characteristic curve (AUC), respectively, via cross-validation., Results: The simple model retained 11 main effects, while the expanded model included 13 main effects and 10 bivariate interactions after backward elimination. HL tests were non-significant for both models (p = 0.50 for the simple model and p = 0.68 for the extended model). Their respective AUC values were 0.789 and 0.790., Conclusion: Leveraging Danish national register data, we developed two predictive models to identify SMI individuals without GP contact. The extended model had slightly better model performance than the simple model. Our study may help to identify persons with SMI not engaging with primary care which could enhance health and treatment outcomes in this group., (© 2024. The Author(s).)

It has long been speculated that psychedelic use could provoke the onset of psychosis, but there is little evidence to support this conjecture. Using a longitudinal research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (n = 9732), we investigated associations between psychedelic use and change in the number of psychotic symptoms during the two-month study period. In covariate-adjusted regression models, psychedelic use during the study period was not associated with a change in the number of psychotic symptoms unless it interacted with a personal or family history of bipolar disorder, in which case the number of symptoms increased, or with a personal (but not family) history of psychotic disorders, in which case the number of symptoms decreased. Taken together, these findings indicate that psychedelic use may affect psychotic symptoms in individuals with a personal or family history of certain disorders characterized by psychotic symptomatology., Competing Interests: Declaration of competing interest PSH has been in paid advisory relationships with the following organizations regarding the development of psychedelics and related compounds: Bright Minds Biosciences Ltd., Eleusis Benefit Corporation, Journey Colab Corporation, Reset Pharmaceuticals Inc., and Silo Pharma. OS was a co-founder of Eudelics AB. Alexander Lebedev is a co-founder of Katharsis Journeys AB., (Copyright © 2024. Published by Elsevier B.V.)

Background: Metabolic Syndrome (MetS) is a risk for developing cardiovascular diseases and its prevalence is especially high in psychiatric patients. To date, there is limited data from the United Arab Emirates (UAE) on the prevalence of MetS. Therefore, we aimed to investigate its prevalence and possible risk factors in a large sample of psychiatric patients in the UAE., Methods: A cross-sectional study was conducted at Al-Ain Hospital, in Al-Ain City, UAE. We collected demographic and clinical data on patients diagnosed with schizophrenia, schizoaffective, and bipolar affective disorder in the period between January 2017 and December 2020. This included their secondary diagnosis (psychiatric or medical), vital signs (heart rate, systolic and diastolic blood pressure, Body Mass Index [BMI]), metabolic parameters (fasting blood glucose, cholesterol, triglycerides, low-density lipoprotein, high-density lipoproteins), and prescribed medications. We used the American Association of Clinical Endocrinology (AACE) criteria to diagnose MetS., Results: We included 889 subjects and of these, 79.8% ( N  = 709) had a BMI ≥25 kg/m 2 and 9.8% ( N  = 87) had no abnormal metabolic parameters. Overall, 28.1% ( N  = 250) had MetS with no statistical difference between the three groups. Fasting blood glucose levels and abnormally elevated triglycerides were significant predictors for MetS., Conclusion: Our study found that around one in three patients had MetS irrespective of the three diagnoses. Some variables were significant predictors for MetS. Our findings were consistent with other studies and warrant the need for regular screening and management of abnormal metabolic parameters.

Objective: There is increasing interest in early intervention and detection strategies for youth at-risk of developing a serious mental illness (SMI). Little is known about early factors that may be related to the later development of a SMI; thus, the aim of this study was to determine what clinical factors might relate to the development of in this study psychosis, bipolar disorder and severe or recurrent major depression in at-risk youth., Method: The sample consisted of 162 youth aged 12-26 years at different stages of risk. Thirty-one participants developed a SMI during the study. Those who made a transition were compared on a range of baseline clinical and functional measures with those who did not make the transition. A Cox regression model was used to assess the association between measures and later development of a SMI., Results: Female sex, attenuated psychotic symptoms as assessed with the Scale of Psychosis-Risk Symptoms (SOPS) and ratings on the K-10 Distress Scale, were found to be significantly associated with the later transition to mental illness. Females were 2.77 times more likely to transition compared to males. For the SOPS and K-10 scales, there is a 14% increase in the transition rate relative to a one-scale increase in SOPS and a 7% increase in the transition rate relative to a one-point increase in the K-10., Conclusions: Results from these longitudinal data provide further insight into the specific clinical measures that may be pertinent in early detection of mental illnesses., 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.

Background: Women with bipolar disorder (BD) are at high risk of postpartum psychosis (PP). The factors that increase risk of PP among women with BD are not fully understood. Here, we examine whether sleep disruption in the perinatal period (poor sleep quality in late pregnancy and sleep deprivation related to childbirth) is associated with PP in a longitudinal study of pregnant women with BD., Methods: Participants were 76 pregnant women with lifetime DSM-5 bipolar I disorder or schizoaffective-BD, followed from week 12 of pregnancy to 12 weeks postpartum. Demographics and lifetime psychopathology were assessed at baseline via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry). Psychopathology and sleep disruption within the current perinatal period were assessed in the third trimester and at 12 weeks postpartum. Data were supplemented by clinician questionnaires and case-note review., Results: After controlling for prophylactic use of mood stabilising medication, the loss of at least one complete night of sleep across labour/delivery was associated with five times the odds of experiencing PP compared to no or less than one night of sleep loss across labour/delivery (OR 5.19, 95 % CI 1.45-18.54; p = 0.011). Sleep quality in late pregnancy was not associated with PP, and perinatal sleep disruption was not associated with postpartum depression., Limitations: Lack of objective measures of sleep factors., Conclusions: In the context of other aetiological factors, severe sleep loss associated with childbirth/the immediate postpartum may act as a final trigger of PP. These findings could have important clinical implications for risk prediction and prevention of PP., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Early identification and intervention of individuals with an increased risk for bipolar disorder (BD) may improve the course of illness and prevent long‑term consequences. Early-BipoLife, a multicenter, prospective, naturalistic study, examined risk factors of BD beyond family history in participants aged 15-35 years. At baseline, positively screened help-seeking participants (screenBD at-risk) were recruited at Early Detection Centers and in- and outpatient depression and attention-deficit/hyperactivity disorder (ADHD) settings, references (Ref) drawn from a representative cohort. Participants reported sociodemographics and medical history and were repeatedly examined regarding psychopathology and the course of risk factors. N = 1,083 screenBD at-risk and n = 172 Ref were eligible for baseline assessment. Within the first two years, n = 31 screenBD at-risk (2.9 %) and none of Ref developed a manifest BD. The cumulative transition risk was 0.0028 at the end of multistep assessment, 0.0169 at 12 and 0.0317 at 24 months (p = 0.021). The transition rate with a BD family history was 6.0 %, 4.7 % in the Early Phase Inventory for bipolar disorders (EPIbipolar), 6.6 % in the Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP) and 3.2 % with extended Bipolar At-Risk - BARS criteria). In comparison to help-seeking young patients from psychosis detection services, transition rates in screenBD at-risk participants were lower. The findings of Early-BipoLife underscore the importance of considering risk factors beyond family history in order to improved early detection and interventions to prevent/ameliorate related impairment in the course of BD. Large long-term cohort studies are crucial to understand the developmental pathways and long-term course of BD, especially in people at- risk., Competing Interests: Declaration of Competing Interest JM, KLB, CB, KL, CS, JM, GJ, AJF, ML, AB, AR, SM, TS, TK, IF, AJ, UD, SKÖ, PFP, LMH, PR, SB, PM, BM and AP state to have no conflict of interest. SKS has received author's and advisory honoraria from Takeda/Shire and Medice Arzneimittel Pütter GmbH in the last 3 years. AR serves on advisory boards and receives speaker's honoraria from Medice, Shire/Takeda, Janssen, neuraxpharm, Servier and SAGE. MB has received grant support from the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung, and the European Commission. He served as a consultant to GH Research, Janssen-Cilag, neuraxpharm, Novartis, Shire International, Sunovion, and Takeda, and received fees from Aristo, Hexal, Janssen-Cilag, and Sunovion. CU Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic., (Copyright © 2023. Published by Elsevier B.V.)

Background and Hypothesis: To clarify whether the familial liability to psychosis associated with bipolar disorder (BD) is nonspecific or has a greater effect on risk for psychosis in cases with prominent mood symptoms and/or a remitting course., Study Design: We examined, in 984 809 offspring raised in intact families in Sweden, born 1980-1996 and followed-up through 2018, by multivariable Cox proportional hazards regression, risk in offspring of parents with BD for 7 psychotic disorders: Psychotic MD (PMD), psychotic BD (PBD), schizoaffective disorder (SAD), acute psychoses, psychosis NOS, delusional disorder (DD) and schizophrenia (SZ). Diagnoses were obtained from national registers., Study Results: In the offspring of BD parents, the hazard ratios (HR) for these 7 disorders formed an inverted U-shaped curve, rising from 2.98 for PMD, to peak at 4.49 for PBD and 5.25 for SAD, and then declining to a HR of 3.48 for acute psychoses and 3.22 for psychosis NOS, to a low of 2.19 for DD and 2.33 for SZ. A similar pattern of risks was seen in offspring of mothers and fathers affected with BD and in offspring predicted from age at onset in their BD parent., Conclusions: The BD-associated risk for psychosis impacts most strongly on mood disorders, moderately on episodic psychotic syndromes, and least on chronic psychotic disorders. These results support prior clinical studies suggesting a qualitative difference in the familial substrate for psychosis occurring in BD and SZ., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This study aimed to identify trajectories of service use during the last year before suicide death and the characteristics associated with the trajectories in patients with substance use disorders., Methods: This study used a national registry data linkage, which included all patients with substance use disorders who died by suicide in Norway between 2010 and 2018. In- and outpatient contacts with mental health or substance use services during the last year before suicide death was analyzed by week using Sequence State Analysis and cluster analysis to identify trajectories. Logistic regression was used to measure the association between the characteristics and the trajectories., Results: We identified four trajectories of service contact. A brief contact trajectory ( n  = 366) with a low proportion of weeks in contact ( M weeks = 8.3), associated with less psychosis or bipolar disorder (aOR = 0.13 (0.08-0.22)) and higher age. A regular contact trajectory ( n  = 160), with a higher proportion of contact ( M weeks = 47.9), associated with psychosis or bipolar disorder (aOR = 3.66 (2.10-6.47)) and depressive or anxiety disorder (aOR = 3.11 (1.93-5.13)). An intermittent contact trajectory ( n  = 195) with most contacts with outpatient substance use disorder services ( M weeks = 9.7). A continuous contact trajectory ( n  = 109) with a high proportion of inpatient contact ( M weeks = 44.5), strongly associated with psychosis or bipolar disorder (aOR = 6.08 (3.26-11.80))., Conclusion: Longitudinal descriptions of service use reveal different trajectories that are important to consider when developing policies or interventions to reduce the risk of suicide death in patients with substance use disorders.

Importance: People with psychosis are more likely to be born and live in densely populated and socioeconomically deprived environments, but it is unclear whether these associations are a cause or consequence of disorder., Objective: To investigate whether trajectories of exposure to deprivation and population density before and after diagnosis are associated with psychotic disorders or nonpsychotic bipolar disorder., Design, Setting, and Participants: This nested case-control study included all individuals born in Sweden between January 1, 1982, and December 31, 2001, diagnosed for the first time with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychotic disorder or nonpsychotic bipolar disorder between their 15th birthday and cohort exit (December 31, 2016). One sex- and birth year-matched control participant per case was selected. Data analysis was performed from July 2021 to June 2023., Exposures: The main exposures were quintiles of neighborhood-level deprivation and population density each year from birth to age 14 years and from first diagnosis until cohort exit., Main Outcomes and Measures: The main outcomes were the odds of a serious mental illness outcome associated with trajectories of deprivation and population density, before and after diagnosis in cases. Group-based trajectory modeling was used to derive trajectories of each exposure in each period. Logistic regression was used to examine associations with outcomes., Results: A total of 53 458 individuals (median [IQR] age at diagnosis in case patients, 23.2 [15.0-34.8] years; 30 746 [57.5%] female), including 26 729 case patients and 26 729 control participants, were studied. From birth to early adolescence, gradients were observed in exposure to deprivation and population density trajectories during upbringing and psychotic disorder, with those in the most vs least deprived (adjusted odds ratio [AOR], 1.17; 95% CI, 1.08-1.28) and most vs least densely populated (AOR, 1.49; 95% CI, 1.34-1.66) trajectories at greatest risk. A strong upward mobility trajectory to less deprived neighborhoods was associated with similar risk to living in the least deprived trajectory (AOR, 1.01; 95% CI, 0.91-1.12). Only 543 case patients (2.0%) drifted into more deprived areas after diagnosis; people with psychotic disorder were more likely to belong to this trajectory (AOR, 1.38; 95% CI, 1.16-1.65) or remain in the most deprived trajectory (AOR, 1.36; 95% CI, 1.24-1.48) relative to controls. Patterns were similar for nonpsychotic bipolar disorder and deprivation but weaker for population density., Conclusions and Relevance: In this case-control study, greater exposure to deprivation during upbringing was associated with increased risk of serious mental illness, but upward mobility mitigated this association. People with serious mental illness disproportionately remained living in more deprived areas after diagnosis, highlighting issues of social immobility. Prevention and treatment should be proportionately located in deprived areas according to need.

Objective: We aim to compare the psychiatric antecedents of schizophrenia (SZ) and bipolar disorder (BD)., Methods: Using the Rochester Epidemiology Project, we searched for residents of Olmsted County that had a diagnosis of SZ or BD. We confirmed each case using DSM-5 criteria and obtained the psychiatric antecedents., Results: We identified 205 cases with first episode psychosis or mania (SZ = 131; BD = 74). The mean age at first visit for mental health reasons was 12.3 ± 6.3 years for SZ and 13.9 ± 5.6 years for BD. The duration of the initial prodrome (time from first mental health visit to first episode) was similar for both groups (SZ 8.3 ± 6.2 years vs BD 7.3 ± 5.9 years). We found that SZ and BD have overlapping antecedents, but SZ was more common in males and in foreign born and had more learning deficits before the first episode. BD was more common in white population and had higher rates of depressive and adjustment disorders prior to first episode. BD also had more affective symptoms, nightmares, and panic attacks before the first episode. Both groups had similarly high rates of substance use (SZ 74 % vs BD 74.3 %), prescription of antidepressants (SZ 46.6 % vs BD 55.4 %) and stimulants (SZ 30.5 % vs BD 22.9 %)., Conclusions: The psychiatric antecedents of SZ and BD usually start during adolescence, overlap, and present in unspecific ways. The initial prodromes are more alike than distinct. Further studies are encouraged to continue looking for specific factors that distinguish the antecedents of these two disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark A. Frye received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories, and has Financial Interest/Stock ownership/Royalties from Chymia LLC. No other declaration of interests from other authors., (Copyright © 2023. Published by Elsevier B.V.)

Background: Mental disorders are burdensome and are associated with increased mortality. Mortality has been researched for various mental disorders, especially in countries with national registries, including the Nordic countries. Yet, knowledge gaps exist around national differences, while also relatively less studies compare mortality of those seeking help for mental disorders in specialized mental healthcare (SMH) by diagnosis. Additional insight into such mortality distributions for SMH users would be beneficial for both policy and research purposes. We aim to describe and compare the mortality in a population of SMH users with the mortality of the general population. Additionally, we aim to investigate mortality differences between sexes and major diagnosis categories: anxiety, depression, schizophrenia spectrum and other psychotic disorders, and bipolar disorder., Methods: Mortality and basic demographics were available for a population of N = 10,914 SMH users in the north of The Netherlands from 2010 until 2017. To estimate mortality over the adult lifespan, parametric Gompertz distributions were fitted on observed mortality using interval regression. Life years lost were computed by calculating the difference between integrals of the survival functions for the general population and the study sample, thus correcting for age. Survival for the general population was obtained from Statistics Netherlands (CBS)., Results: SMH users were estimated to lose 9.5 life years (95% CI: 9.4-9.6). Every major diagnosis category was associated with a significant loss of life years, ranging from 7.2 (95% CI: 6.4-7.9) years for anxiety patients to 11.7 (95% CI: 11.0-12.5) years for bipolar disorder patients. Significant differences in mortality were observed between male SMH users and female SMH users, with men losing relatively more life years: 11.0 (95% CI: 10.9-11.2) versus 8.3 (95% CI: 8.2-8.4) respectively. This difference was also observed between sexes within every diagnosis, although the difference was insignificant for bipolar disorder., Conclusion: There were significant differences in mortality between SMH users and the general population. Substantial differences were observed between sexes and between diagnoses. Additional attention is required, and possibly specific interventions are needed to reduce the amount of life years lost by SMH users., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Bipolar disorder (BD) is a mental disorder characterized by mood shifts from severe depression to mania. Pregnant women with BD may experience manic or depressive episodes, so they are usually concerned about the effects of BD on their pregnancy. The aim of this systematic review is to determine the effects of BD on maternal health and fetal health, weight, and development. It also addresses how BD affects the probability of incidence of pregnancy complications in women with bipolar compared with healthy controls., Methods: Seven electronic databases (Ovid MEDLINE, Embase, MIDRIS, APA PsychINFO, Scopus, Web of Science, and ScienceOpen) were searched, and 1728 eligible studies were identified. After deduplication, screening, and manual search processes, we included only 15 studies. Descriptive analysis, and calculation of the probability of incidence for each pregnancy outcome were used to analyze the results., Results: The findings of the included studies suggest that BD during pregnancy may affect both fetal growth and maternal health by increasing the risk of giving birth to an infant with some birth defects such as microcephaly, CNS problems, small for gestational age, and other congenital anomalies, in addition to causing some obstetric complications such as gestational hypertension, preterm labor, need for assisted delivery, hospital readmission, and others., Conclusion: Bipolar disorder during pregnancy negatively affects mothers and their fetuses and increases the probability of incidence of obstetrics complications., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Describe symptoms before and at time of register-diagnosis in children and adolescents., Methods: A random sample was selected for chart-review from a Danish nationwide cohort of patients <18 years registered with an incident ICD-10 register-diagnosis of single hypomanic/manic episode or bipolar disorder between 1995 and 2014. Patients with symptoms which adequately documented a BD diagnosis in the chart were included for analysis., Results: 521 were diagnosed in the study period. A random sample of 25% were selected, and 106 charts were possible to retrieve, with 48 chart reviews resulting in confirmation of diagnosis. Time from first reported affective symptoms to diagnosis was 2.6 ± 2.7 years for depressive symptoms, 2.5 ± 2.9 years for mixed symptoms, 1.4 ± 1.6 years for hypomanic symptoms, and 0.4 ± 0.5 years for manic symptoms. A hierarchical clustering analysis revealed three patient-profiles: primarily hypomanic/manic, primarily depressive, and more rare, primarily mixed profile. Frequently reported symptoms prior to diagnosis include anhedonia (79%), irritability (71%), hyperactivity (62.5%), decreased energy (62.5%), and psychotic symptoms (52%).Symptoms of ADHD (19%), comorbid ADHD (15%), symptoms of anxiety (52%), comorbid anxiety (4%), suicidal thoughts (50%), suicide attempts (8%), cutting (23%), substance misuse (21%), and criminal activity (10%) were reported before incident BD diagnosis., Conclusion: The observed patient-profiles leading to diagnosis were primarily manic or depressive, resembling presentations in adults. The presence of ADHD, anxiety, suicide attempts, cutting, and criminal activity prior to diagnosis emphasizes the need for treatment of children and adolescents with affective symptoms. The gap from appearance of the symptoms to diagnosis suggests a window for earlier treatment.

People with severe mental illness (SMI), such as major depression, bipolar disorder, and schizophrenia, experience numerous risk factors that may predispose them to food insecurity; however, the prevalence of food insecurity and its effects on health are under-researched in this population group. This systematic review and meta-analysis aimed to describe the prevalence and correlates of food insecurity in people with SMI. A comprehensive electronic search was conducted up to March 2021. Random effects meta-analysis was employed to determine the prevalence of food insecurity in SMI, and odds ratio (OR) of food insecurity in people with SMI compared to non-psychiatric controls/general population. Twenty-nine unique datasets (31 publications) were included. Prevalence estimate of food insecurity in people with SMI was 40% (95% CI 29-52%, I 2 = 99.7%, N  = 27). People with SMI were 2.71 (95% CI 1.72-3.25) times more likely to report food insecurity than the comparator group ( Z  = 11.09, p  < 0.001, I 2 = 95%, N  = 23). The odds of food insecurity in SMI were higher in high/high-middle income countries compared to low/low-middle income countries, likely due to the high food insecurity rates in the general population of lower income countries. There was no difference in food insecurity rates by diagnosis. Food insecurity should be a consideration for health professionals working with community-dwelling people with SMI.

Background: The jumping to conclusions (JTC) bias, ie, making decisions based on inadequate evidence, is associated with psychosis in adults and is believed to underlie the formation of delusions. Knowledge on the early manifestations of JTC and its associations with psychotic experiences (PE) in children and adolescents is lacking., Design: Preadolescent children (mean age 11.9 y, SD 0.2) at familial high risk of schizophrenia (FHR-SZ, n = 169) or bipolar disorder (FHR-BP, n = 101), and controls (n = 173) were assessed with the Beads Task to examine JTC. The number of beads drawn before making a decision, "draws to decision" (DTD) was used as a primary outcome. PE were ascertained in face-to-face interviews. General intelligence was measured with Reynolds Intellectual Screening Test., Results: Children at FHR-SZ took fewer DTD than controls (4.9 vs 5.9, Cohen's d = 0.31, P = .004). Differences were attenuated when adjusting for IQ (Cohen's d = 0.24, P = .02). Higher IQ was associated with a higher number of DTD (B = 0.073, P < .001). Current subclinical delusions compared with no PE were associated with fewer DTD in children at FHR-SZ (P = .04) and controls (P < .05). Associations between delusions and DTD were nullified when accounting for IQ., Conclusions: JTC marks familial risk of psychosis in preadolescence, not reducible to general intelligence. JTC is associated with subclinical delusions, but this may be an expression of intellectual impairment. Future studies should establish temporality between JTC and delusion formation and examine JTC as a target for early intervention., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: It is unclear whether there are differences between specific school subject performance and later psychiatric disorders. We examined whether mean grade point average (MGPA) and specific school subjects associated with diagnoses of nonaffective psychoses, bipolar disorder and depression., Methods: In this register-based study, we studied the Finnish population born in 1987 who had available MGPA and six specific school grades (age = 15.4-16.4 years; n = 50,508). Grades were analyzed with smoothing splines. Covariates included sex, urbanicity, parental education level and parental diagnosed psychiatric disorders. Outcomes were incident nonaffective psychosis, bipolar disorder and depression diagnosed in specialized services until year 2015 (age = 28.0-28.9 years)., Results: During the follow-up, 727 individuals were diagnosed with nonaffective psychoses, 489 with bipolar disorder and 3492 with depression. MGPA was inversely associated with all outcomes. In multivariate models including specific school subjects and covariates, the school subject with largest risk ratios (RR) was Physical Education (RR and Bonferroni-corrected confidence interval [CI] at -1.5 SD: nonaffective psychoses 1.63, 1.36-1.95; bipolar disorder 1.64, 1.30-2.05; depression 1.72, 1.53-1.93). Higher grades in Art were associated with nonaffective psychoses and depression (RR and Bonferroni-corrected CI at +1.5 SD: nonaffective psychoses 1.48, 1.11-1.96; depression 1.22, 1.07-1.38)., Conclusion: There was a robust association between poorer scores on Physical Education and risk for psychosis, bipolar disorder and depression. Higher grades in Art were also associated with risk for later disorders. Subject specific school performance may be more informative about mental disorder risk than overall school performance., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Importance: The nature of the genetic relationship between major depression and bipolar disorder remains unclear and might be clarified by considering disorders outside of the mood spectrum., Objective: To better understand the relationship between genetic liabilities for major depression (MD) and bipolar disorder (BD)., Design, Setting, and Participants: A cohort study was conducted with data for individuals born in Sweden to Swedish parents from 1960 to 1990, with follow-up through December 31, 2018. The data included family genetic risk scores for MD and BD and International Classification of Diseases codes for a range of disorders as reported in primary care, specialist, and hospital registries. Data analysis was conducted from April 2022 to July 2022., Exposures: High and low genetic liability were defined as being in the upper and lower 2 risk deciles. Risk was compared in individuals at high genetic liability to (1) MD only, (2) BD only, and (3) both MD and BD and those at (4) high genetic liability to BD and low genetic liability to MD and (5) high genetic liability to MD and low genetic liability to BD., Main Outcomes and Measures: Risk for nonpsychotic MD and BD, psychotic MD and BD, anxiety disorders, obsessive-compulsive disorder, schizoaffective disorder (SAD), schizophrenia, and other nonaffective psychosis., Results: Data were included for 2 736 950 individuals with a mean (SD) age at follow-up of 43.9 (9.1) years. High genetic liability to only BD increased risk for nonpsychotic BD, psychotic BD, and SAD. High genetic liability to only MD augmented risk for nonpsychotic MD, anxiety disorders, and nonpsychotic BD. High genetic liability to both BD and MD had the strongest association with risk for nonpsychotic BD, anxiety disorders, and nonpsychotic MD. High genetic liability to BD and low genetic liability to MD increased risk for psychotic BD, nonpsychotic BD, and SAD with no increased risk for nonpsychotic MD or anxiety disorders. High genetic liability to MD and low genetic liability to BD increased risk for nonpsychotic MD, nonpsychotic BD, and anxiety disorders with no increased risk for psychotic BD., Conclusions and Relevance: In this study, hypotheses that BD and MD are either genetically distinct or genetically closely interrelated were not supported. Both BD and MD were associated with a genetic vulnerability to mood disorders, but even that liability was partially selective. However, compared with individuals at high liability to MD, those at elevated genetic liability for BD had a substantially increased risk for psychosis. Compared with individuals at elevated genetic liability to BD, those at high genetic risk for MD had a considerably augmented risk for anxiety disorders. Clarifying genetic relationships between psychiatric syndromes can be substantially aided by the consideration of profiles of risk for a range of disorders.

Psychotic symptoms, that we defined as delusions or hallucinations, are common in bipolar disorders (BD). This systematic review and meta-analysis aims to synthesise the literature on both lifetime and point prevalence rates of psychotic symptoms across different BD subtypes, including both BD type I (BDI) and BD type II (BDII). We performed a systematic search of Medline, PsycINFO, Embase and Cochrane Library until 5 August 2021. Fifty-four studies ( N = 23 461) of adults with BD met the predefined inclusion criteria for evaluating lifetime prevalence, and 24 studies ( N = 6480) for evaluating point prevalence. Quality assessment and assessment of publication bias were performed. Prevalence rates were calculated using random effects meta-analysis, here expressed as percentages with a 95% confidence interval (CI). In studies of at least moderate quality, the pooled lifetime prevalence of psychotic symptoms in BDI was 63% (95% CI 57.5-68) and 22% (95% CI 14-33) in BDII. For BDI inpatients, the pooled lifetime prevalence was 71% (95% CI 61-79). There were no studies of community samples or inpatient BDII. The pooled point prevalence of psychotic symptoms in BDI was 54% (95 CI 41-67). The point prevalence was 57% (95% CI 47-66) in manic episodes and 13% (95% CI 7-23.5) in depressive episodes. There were not enough studies in BDII, BDI depression, mixed episodes and outpatient BDI. The pooled prevalence of psychotic symptoms in BDI may be higher than previously reported. More studies are needed for depressive and mixed episodes and community samples.Prospero registration number: CRD 42017052706.

Objective: Although frequently reported in psychosis, obsessive-compulsive symptoms (OCS) are often not recognized and thus undertreated. We aimed to estimate the prevalence of OCS and obsessive-compulsive disorder (OCD) in patients with schizophrenia, schizoaffective disorder, or bipolar disorder in clinical records and identify clinical associations of OCS co-occurrence., Methods: Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre case register. The study population was restricted to individuals diagnosed with schizophrenia ( ICD F20.x), schizoaffective disorder ( ICD F25.x), or bipolar disorder ( ICD F31.x) between 2007 and 2015. OCS and OCD were ascertained from structural fields and via Natural Language Processing software applied to free-text records. Clinical characteristics were obtained from Health of the Nation Outcome Scales for the analyses on associations between clinical characteristics and OCS/OCD status using logistic regressions with confounders considered., Results: 22,551 cases of schizophrenia, schizoaffective disorder, or bipolar disorder were identified in the observation window. Among these, 5,179 (24.0%) were identified as having OCS (including an OCD diagnosis) and 2,574 (11.9%) specifically with comorbid OCD. OCS/OCD was associated with an increased likelihood of recorded aggressive behavior (OR = 1.18; 95% CI, 1.10-1.26), cognitive problems (OR = 1.21; 95% CI, 1.13-1.30), hallucinations and delusions (OR = 1.11; 95% CI, 1.04-1.20), and physical problems (OR = 1.17; 95% CI, 1.09-1.26)., Conclusions: OCS and OCD are frequently recorded for patients with schizophrenia, schizoaffective disorder, and bipolar disorder and are associated with more severe psychiatric clinical characteristics. Automated information extraction tools hold potential to improve recognition and treatment of co-occurring OCS/OCD for psychosis., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Objective: Psychotic experiences are common in children and adolescents and are associated with concurrent and subsequent psychopathology. Most findings originate from general population studies, whereas little is known of the clinical outcomes of psychotic experiences in children and adolescents at familial high risk of psychosis. We examined the prevalence of psychotic experiences in middle childhood and whether early childhood psychotic experiences and developmental pathways of psychotic experiences predicted mental disorders in middle childhood in children at familial high risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and a population-based control group., Methods: In a longitudinal population-based cohort study children at FHR-SZ (N=170), FHR-BP (N=103), and the control group (N=174) were assessed for psychotic experiences and axis I disorders with face-to-face interviews in early and middle childhood (at 7 and 11 years of age)., Results: Psychotic experiences were more prevalent in children at FHR-SZ (31.8%, odds ratio 2.1, 95% CI 1.3-3.4) than in the control group (18.4%) in middle childhood. Early childhood psychotic experiences predicted mental disorders in middle childhood after adjusting for early childhood disorders and familial risk (odds ratio 2.0, 95% CI 1.2-3.1). Having three or more psychotic experiences increased odds the most (odds ratio 2.5, 95% CI 1.1-5.7). Persistent psychotic experiences were associated with increased odds of middle childhood disorders (odds ratio 4.1, 95% CI 2.1-8.4). Psychotic experiences were nondifferentially associated with mental disorders across the three familial risk groups., Conclusions: Early childhood psychotic experiences predict mental disorders in middle childhood. Psychotic experiences index vulnerability for psychopathology nondifferentially in children at familial high risk and the control group. Psychotic experiences should be included in mental health screenings including children at familial high risk.

Objective: Increasing number of people have been prescribed antipsychotics (APs) off-label in recent decades. This study aimed to identify the characteristics and predictors of receiving prescription of antipsychotics off-label., Methods: The study sample was part of the Northern Finland Birth Cohort 1966 (n = 7071). Data included questionnaires and national register data. Information on prescribed medications was extracted from the national register. The sample was divided into three groups: Persons who had been prescribed APs off-label (n = 137), individuals with non-psychotic mental disorders without APs off label (n = 1478) and individuals who had been diagnosed with psychosis or bipolar disorder and who had been prescribed APs (n = 151). We compared sociodemographic, lifestyle and clinical characteristics between the off-label and the comparison groups using logistic regression., Results: The most common diagnoses in the off-label group were depression (n = 96, 70.1%) and anxiety (n = 55, 40.1%). Compared with individuals with non-psychotic mental disorders who were not prescribed APs off-label, individuals with prescribed off-label APs had a lower level of education, lower socioeconomic status, were less often married, had a higher level of somatic and psychiatric morbidity, were more often smokers and more often had a substance abuse disorder and heavy alcohol consumption. When comparing the off-label group to individuals with psychosis or bipolar disorder who used APs, there were less differences, though individuals with psychosis or bipolar disorder had more markers of morbidity and a lower level of education., Conclusion: Individuals who had been prescribed APs off label had a higher level of mental and somatic morbidity and poorer socioeconomic status than individuals with non-psychotic mental disorders who did not use APs., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Objective: Although electroconvulsive therapy (ECT) is anti-suicidal, it is not known whether the presence of suicidal ideation (SI) at baseline predicts response and remission after ECT. The aim of the study was to analyze the impact of baseline SI on response and remission following ECT treatment in a large sample of patients with depression and to assess SI before and after ECT., Methods: This population-based register study used data from the Swedish National Quality Register for ECT and the Swedish Patient Register. Patients aged 18 years or older who had received ECT for a unipolar or bipolar depressive episode between 2011 and 2018 were included in the study. SI was defined as a score of ≥4 on the last item of the Montgomery-Åsberg Depression Rating Scale - Self Assessment (MADRS-S). Using a logistic regression model, SI at baseline was used to predict response and remission following ECT, while controlling for depression severity, psychotic symptoms, presence of a comorbid personality disorder, age, sex, electrode position, unipolar or bipolar disorder, and number of previous suicide attempts at baseline., Results: In patients who exhibited SI at baseline, 53.7% (N = 632) of cases showed a response to ECT, whereas 68.4% (N = 690) of patients without SI showed a response. In addition, 27.2% (N = 320) of cases with SI achieved remission, whereas 48.5% (N = 489) of cases without SI achieved remission. The odds of achieving response and remission for patients with SI were 0.75 and 0.58 times, respectively, those for patients without SI. Of the 1178 patients with pre-treatment SI, 75.64% (N = 891) exhibited no SI at the end of treatment. Moreover, in this subgroup, the presence of a personality disorder, higher MADRS-S-score, and younger age were associated with persistent SI., Conclusion: The presence of SI was associated with lower ECT response and remission rates. Nevertheless, depressive symptoms and SI were reduced in a large proportion of patients across both patient groups. Clinicians should be aware of the lower likelihood of achieving a successful outcome following ECT in younger patients who present with a non-psychotic depressive episode, SI, and (suspected) personality disorders. More research is warranted regarding if these patients can achieve similar or better results with other treatments., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of 'at-risk' cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population., Method: Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12-30) presenting to mental health services., Results: Of 2330 individuals assessed longitudinally, 4.3% ( n = 100) met criteria for new-onset FT BD and 2.2% ( n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression., Conclusions: Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.

Aim: Most of the available data on the prevalence and impact of psychotic symptoms on the course of bipolar disorder (BD) is from Western countries. We aimed to study the prevalence of at least one psychotic episode in the lifetime in patients with BD and its association with the long-term course and outcome., Methodology: 773 patients recruited as part of the Bipolar Disorder Course and Outcome study from India (BiD-CoIN study) were divided into 2 groups, based on the presence or absence of at least one psychotic episode in the lifetime., Results: 326 (42.2%) patients had at least one psychotic episode in their lifetime. At least one psychotic episode in the lifetime was associated with overall more severe illness in terms of lower age of onset, a higher number of episodes in the first 5 years of illness; higher rates of BD-II, a higher rate of lifetime history of at least 1 suicide attempt, lifetime history of hospitalization, history of receiving Electroconvulsive Therapy, and a higher prescription rates of antipsychotics. However, presence of psychotics symptoms was associated with better cognitive functioning., Conclusions: Our findings suggest that the presence of psychotic symptoms during episodes in patients with BD is associated with poorer course of BD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Psychotic disorder not otherwise specified (PNOS) is considered part of the psychosis spectrum, together with schizophrenia spectrum disorders (SSD) and psychotic bipolar spectrum disorders (PBD). The atypical clinical presentations of PNOS conditions may lead to uncertainty regarding treatment choices and expected outcomes. PNOS is understudied, and little is known about patients' premorbid characteristics including premorbid adjustment, prevalence of early cannabis use and childhood trauma. Knowledge about early illness phases can increase our understanding of this diagnostic group., Methods: We included 1099 participants from the Norwegian TOP-study; 688 with narrow SSD diagnoses (schizophrenia, schizoaffective disorder, schizophreniform disorder), 274 with PBD (psychotic bipolar 1 and bipolar NOS) and 137 with PNOS diagnosed with the SCID-I for DSM-IV. Participants were assessed with the Premorbid Adjustment Scale (PAS) divided into the areas of premorbid academic and social functioning. We obtained information on age at first exposure to cannabis and use of cannabis before the age of 16. The participants also provided information regarding early traumatic experiences using the Childhood Trauma Questionnaire (CTQ)., Results: Participants with PNOS and SSD had poorer premorbid academic functioning than those with PBD (F 2, 1029  = 7.81, p < 0.001, p η 2  = 0.015). Premorbid social adjustment was significantly worse in the SSD group compared to the PBD group (F 2, 1024  = 3.10, p = 0.045, p η 2  = 0.006), with PNOS in the middle position. Significantly more of the participants with PNOS (17.5%) and SSD (11.5%) used cannabis before the age of 16 compared with PBD (5.3%, Wald χ 2  = 6.86, p = 0.03). There were no significant differences between the three groups regarding mean CTQ scores or in the proportion of participants who had experienced at least one type of childhood adversity., Conclusions: Participants with PNOS appear as more similar to participants with SSD than to those with PBD regarding early premorbid adjustment and early cannabis use. The results indicate that many conditions classified as PNOS have functional impairments and problematic substance use from an early age. The prevalence of childhood adversities are high in all three groups., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Manic episodes are a defining, frequent and dramatically disabling occurrence in the course of Bipolar Disorder type I. Current pharmacotherapy of mania lists a good number of agents, but differences in efficacy and safety profiles among these agents must be considered in order to tailor personalized therapies, especially when the long-term course of the illness is considered. There is wide room and need to ameliorate current pharmacological approaches to mania, but ongoing pharmacological research on the topic is scant. In this work we try to critically assess clinical factors and patients' characteristics that may influence the treatment choice for manic episodes. In addition, we conduct a narrative review on experimental pharmacology of bipolar mania and psychotic disorders, presenting a critical overview on agents which could represent treatment alternatives for a manic episode in the next future. Results show limited novel or ongoing research on agents acting as mood stabilizers (Ebselen, Valnoctamide and Eslicarbazepine did not reach statistical significance in demonstrating antimanic efficacy). As for the emerging experimental antipsychotic, some of them (including KarXT, SEP-363856, RO6889450, ALKS3831) have demonstrated good antipsychotic efficacy and a favorable safety profile, but little is known about their use in patients with bipolar disorder and specifically designed trials are needed. Lastly, some benefits for the treatment of mania could be expected to come in the next future from non-mood stabilizers/non-antipsychotic agents (especially PKC inhibitors like Endoxifen): long-term trials are needed to confirm positive results in terms of long-term efficacy and safety., (© 2022. The Author(s).)

Background To compare estimated 10-year and 30-year cardiovascular risk in primary care patients with and without serious mental illness (SMI; bipolar disorder, schizophrenia, or schizoaffective disorder). Methods and Results All patients aged 18 to 75 years with a primary care visit in January 2016 to September 2018 were included and were grouped into those with and without SMI using diagnosis codes. Ten-year cardiovascular risk was estimated using atherosclerotic cardiovascular disease scores for patients aged 40 to 75 years without cardiovascular disease; 30-year cardiovascular risk was estimated using Framingham risk scores for patients aged 18 to 59 years without cardiovascular disease. Demographic, vital sign, medication, diagnosis, and health insurance data were collected from the electronic health record by a clinical decision support system. Descriptive statistics examined unadjusted differences, while general linear models examined differences for continuous variables and logistic regression models for categorical variables. Models were then adjusted for age, sex, race, ethnicity, and insurance type. A total of 11 333 patients with SMI and 579 924 patients without SMI were included. After covariate adjustment, 10-year cardiovascular risk was significantly higher in patients with SMI (mean, 9.44%; 95% CI, 9.29%-9.60%) compared with patients without SMI (mean, 7.99%; 95% CI, 7.97-8.02). Similarly, 30-year cardiovascular risk was significantly higher in those with SMI (25% of patients with SMI in the highest-risk group compared with 11% of patients without SMI; P <0.001). The individual cardiovascular risk factors contributing most to increased risk for those with SMI were elevated body mass index and smoking. Among SMI subtypes, patients with bipolar disorder had the highest 10-year cardiovascular risk, while patients with schizoaffective disorder had the highest 30-year cardiovascular risk. Conclusions The significantly increased cardiovascular risk associated with SMI is evident even in young adults. This suggests the importance of addressing uncontrolled major cardiovascular risk factors in those with SMI at as early an age as possible. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02451670.

Importance: Adults with schizophrenia, schizoaffective disorder, or bipolar disorder, collectively termed serious mental illness (SMI), have shortened life spans compared with people without SMI. The leading cause of death is cardiovascular (CV) disease., Objective: To assess whether a clinical decision support (CDS) system aimed at primary care clinicians improves CV health for adult primary care patients with SMI., Design, Setting, and Participants: In this cluster randomized clinical trial conducted from March 2, 2016, to September 19, 2018, restricted randomization assigned 76 primary care clinics in 3 Midwestern health care systems to receive or not receive a CDS system aimed at improving CV health among patients with SMI. Eligible clinics had at least 20 patients with SMI; clinicians and their adult patients with SMI with at least 1 modifiable CV risk factor not at the goal set by the American College of Cardiology/American Heart Association guidelines were included. Statistical analysis was conducted on an intention-to-treat basis from January 10, 2019, to December 29, 2021., Intervention: The CDS system assessed modifiable CV risk factors and provided personalized treatment recommendations to clinicians and patients., Main Outcomes and Measures: Patient-level change in total modifiable CV risk over 12 months, summed from individual modifiable risk factors (smoking, body mass index, low-density lipoprotein cholesterol level, systolic blood pressure, and hemoglobin A1c level)., Results: A total of 80 clinics were randomized; 4 clinics were excluded for having fewer than 20 eligible patients, leaving 42 intervention clinics and 34 control clinics. A total of 8937 patients with SMI (4922 women [55.1%]; mean [SD] age, 48.4 [13.5] years) were enrolled. There was a 4% lower rate of increase in total modifiable CV risk among intervention patients relative to control patients (relative rate ratio [RR], 0.96; 95% CI, 0.94-0.98). The intervention favored patients who were 18 to 29 years of age (RR, 0.89; 95% CI, 0.81-0.98) or 50 to 59 years of age (RR, 0.93; 95% CI, 0.90-0.96), Black (RR, 0.93; 95% CI, 0.88-0.98), or White (RR, 0.96; 95% CI, 0.94-0.98). Men (RR, 0.96; 95% CI, 0.94-0.99) and women (RR, 0.95; 95% CI, 0.92-0.97), as well as patients with any SMI subtype (bipolar disorder: RR, 0.96; 95% CI, 0.94-0.99; schizoaffective disorder: RR, 0.94; 95% CI, 0.90-0.98; schizophrenia: RR, 0.92; 95% CI, 0.85-0.99) also benefited from the intervention. Despite treatment effects favoring the intervention, there were no significant differences in individual modifiable risk factors., Conclusions and Relevance: This CDS intervention resulted in a rate of change in total modifiable CV risk that was 4% lower among intervention patients compared with control patients. Results were driven by the cumulative effects of incremental and mostly nonsignificant changes in individual modifiable risk factors. These findings emphasize the value of using CDS to prompt early primary care intervention for adults with SMI., Trial Registration: ClinicalTrials.gov Identifier: NCT02451670.

Objective: Evidence suggests that individuals with autism spectrum disorder have increased rates of co-occurring psychosis and/or bipolar disorder. Considering the peak age of onset for psychosis and bipolar disorder occurs in adulthood, we investigated the co-occurrence of these disorders in adults with autism., Methods: We conducted a systematic review and meta-analysis (PROSPERO Registration Number: CRD42018104600) to (1) examine the prevalence of psychosis and bipolar disorder in adults with autism, and (2) review potential risk factors associated with their co-occurrence., Results: Fifty-three studies were included. The pooled prevalence for the co-occurrence of psychosis in adults with autism was 9.4 % (N = 63,657, 95 %CI = 7.52, 11.72). The pooled prevalence for the co-occurrence of bipolar disorders in adults with autism was 7.5 % (N = 31,739, 95 %CI = 5.79, 9.53)., Conclusions: Psychosis and bipolar disorder occur at a substantially higher prevalence in adults with autism compared to general population estimates. While there is an overall dearth of research examining risk factors for these disorders in autism, males had increased likelihood of co-occurring psychosis, and females of co-occurring bipolar disorder. These results highlight the need for ongoing assessment and monitoring of these disorders in adults with autism., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bipolar Disorder (BD) is a mental disorder which frequently requires long hospitalizations and need for acute psychiatric care. The aim of this study was to describe a nationwide perspective of BD related hospitalizations and to use a BigData based approach in mental health research. We performed a retrospective observational study using a nationwide hospitalization database containing all hospitalizations registered in Portuguese public hospitals from 2008-2015. Hospitalizations with a primary diagnosis of BD were selected based on International Classification of Diseases version 9, Clinical Modification (ICD-9-CM) codes of diagnosis 296.xx (excluding 296.2x; 296.3x and 296.9x). From 20,807 hospitalizations belonging to 13,300 patients, around 33.4% occurred in male patients with a median length of stay of 16.0 days and a mean age of 47.9 years. The most common hospitalization diagnosis in BD has the code 296.4x (manic episode) representing 34.3% of all hospitalizations, followed by the code 296.5x (depressed episode) with 21.4%. The mean estimated hospitalization charge was 3,508.5€ per episode, with a total charge of 73M€ in the 8-year period of this study.This is a nationwide study giving a broad perspective of the BD hospitalization panorama at a national level. We found important differences in hospitalization characteristics by sex, age and primary diagnosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Bipolar disorder (BD) is a chronic and severe psychiatric disease. There are often significant delays prior to diagnosis, and only 30 to 40 % of patients will experience complete remission. Since BD occurs most often at a young age, the disorder can seriously obstruct future socio-professional development and integration. Vulnerability-stress model of BD is considered to be the result of an interaction between vulnerability genes and environmental risk factors, which leads to the onset of the disorder most often in late adolescence or early adulthood. The clinical "staging" model of BD situates the subject in a clinical continuum of varying degrees of severity (at-risk status, first episode, full-blown BD). Given the demonstrated effectiveness of early intervention in the early stages of psychotic disorder, we posit that early intervention for early stages of BD (i.e. at-risk status and first episode mania or hypomania) would reduce the duration of untreated illness and optimize the chances of therapeutic response and recovery., Methods: We conducted a narrative review of the literature to gather updated data on: (1) features of early stages: risk factors, at-risk symptoms, clinical specificities of the first manic episode; (2) early screening: targeted populations and psychometric tools; (3) early treatment: settings and therapeutic approaches for the early stages of BD., Results: (1) Features of early stages: among genetic risk factors, we highlighted the diagnosis of BD in relatives and affective temperament including as cyclothymic, depressive, anxious and dysphoric. Regarding prenatal environmental risk, we identified peripartum factors such as maternal stress, smoking and viral infections, prematurity and cesarean delivery. Later in the neurodevelopmental course, stressful events and child psychiatric disorders are recognized as increasing the risk of developing BD in adolescence. At-risk symptoms could be classified as "distal" with early but aspecific expressions including anxiety, depression, sleep disturbance, decreased cognitive performance, and more specific "proximal" symptoms which correspond to subsyndromic hypomanic symptoms that increase in intensity as the first episode of BD approaches. Specific clinical expressions have been described to assess the risk of BD in individuals with depression. Irritability, mixed and psychotic features are often observed in the first manic episode. (2) Early screening: some individuals with higher risk need special attention for screening, such as children of people with BD. Indeed, it is shown that children with at least one parent with BD have around 50 % risk of developing BD during adolescence or early adulthood. Groups of individuals presenting other risk factors, experiencing an early stage of psychosis or depressive disorders should also be considered as targeted populations for BD screening. Three questionnaires have been validated to screen for the presence of at-risk symptoms of BD: the Hypomanic Personality Scale, the Child Behavior Checklist-Paediatric Bipolar Disorder, and the General Behavior Inventory. In parallel, ultra-high risk criteria for bipolar affective disorder ("bipolar at-risk") distinguishing three categories of at-risk states for BD have been developed. (3) Early treatment: clinical overlap between first psychotic and manic episode and the various trajectories of the at-risk status have led early intervention services (EIS) for psychosis to reach out for people with an early stage of BD. EIS offers complete biopsychosocial evaluations involving a psychiatric examination, semi-structured interviews, neuropsychological assessments and complementary biological and neuroimaging investigations. Key components of EIS are a youth-friendly approach, specialized and intensive care and client-centered case management model. Pharmaceutical treatments for at-risk individuals are essentially symptomatic, while guidelines recommend the use of a non-antipsychotic mood stabilizer as first-line monotherapy for the first manic or hypomanic episode. Non-pharmacological approaches including psychoeducation, psychotherapy and rehabilitation have proven efficacy and should be considered for both at-risk and first episode of BD., Conclusions: EIS for psychosis might consider developing and implementing screening and treatment approaches for individuals experiencing an early stage of BD. Several opportunities for progress on early intervention in the early stages of BD can be drawn. Training first-line practitioners to identify at-risk subjects would be relevant to optimize screening of this population. Biomarkers including functional and structural imaging measures of specific cortical regions and inflammation proteins including IL-6 rates constitute promising leads for predicting the risk of transition to full-blown BD. From a therapeutic perspective, the use of neuroprotective agents such as folic acid has shown particularly encouraging results in delaying the emergence of BD. Large-scale studies and long-term follow-up are still needed to achieve consensus in the use of screening and treatment tools. The development of specific recommendations for the early stages of BD is warranted., (Copyright © 2021 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Many patients with bipolar disorder (BD) are initially misdiagnosed with major depressive disorder (MDD) and are treated with antidepressants, whose potential iatrogenic effects are widely discussed. It is unknown whether MDD is a comorbidity of BD or its earlier stage, and no consensus exists on individual conversion predictors, delaying BD's timely recognition and treatment. We aimed to build a predictive model of MDD to BD conversion and to validate it across a multi-national network of patient databases using the standardization afforded by the Observational Medical Outcomes Partnership (OMOP) common data model. Five "training" US databases were retrospectively analyzed: IBM MarketScan CCAE, MDCR, MDCD, Optum EHR, and Optum Claims. Cyclops regularized logistic regression models were developed on one-year MDD-BD conversion with all standard covariates from the HADES PatientLevelPrediction package. Time-to-conversion Kaplan-Meier analysis was performed up to a decade after MDD, stratified by model-estimated risk. External validation of the final prediction model was performed across 9 patient record databases within the Observational Health Data Sciences and Informatics (OHDSI) network internationally. The model's area under the curve (AUC) varied 0.633-0.745 (µ = 0.689) across the five US training databases. Nine variables predicted one-year MDD-BD transition. Factors that increased risk were: younger age, severe depression, psychosis, anxiety, substance misuse, self-harm thoughts/actions, and prior mental disorder. AUCs of the validation datasets ranged 0.570-0.785 (µ = 0.664). An assessment algorithm was built for MDD to BD conversion that allows distinguishing as much as 100-fold risk differences among patients and validates well across multiple international data sources., (© 2021. The Author(s).)

Severe mental disorders are associated with a life expectancy that is 10-20 years shorter than the general population's. The prevalence of cigarette smoking in these populations is very high. We examined the effect of smoking on life expectancy and survival in patients with a diagnosis of schizophrenia, schizoaffective disorder or bipolar affective disorder from 2007 to 2018 in South East London, UK. Smoking status was determined using unstructured text data extracted from electronic health records. A total of 21,588 patients were identified of which 16,717, (77.4%) were classified as current smokers and 3438 (15.9%) as non-smokers. In female participants, life expectancy at birth was 67.6 years in current smokers (95% CI: 66.4-68.8) and 74.9 years in non-smokers (95% CI: 72.8-77.0), a difference of 7.3 years. In male participants, life expectancy at birth was 63.5 years in current smokers (95% CI: 62.5-64.5) and 68.5 years in non-smokers (95% CI, 64.4-72.6), a difference of 5.0 years. Adjusted survival models found that current smoking status was associated with an increased mortality risk for both females (aHR: 1.42, 95% CI: 1.21-1.66, p < 0.001) and males (aHR: 1.49; 95% CI: 1.25-1.79, p < 0.001). In terms of the effect sizes, these risks were similar to those associated with a diagnosis of co-morbid alcohol or opioid use disorder. Smoking may account for a substantial proportion of the reduced life expectancy in patients with psychotic disorders. Increased emphasis on reducing cigarette smoking in these populations may be the most effective way to reduce the mortality gap with the general population., (Copyright © 2018. Published by Elsevier B.V.)

Background: For more than 150 years, controversy over the status of post-partum psychosis has hindered research and caused considerable confusion for clinicians and women, with potentially negative consequences. We aimed to explore the hypothesis that genetic vulnerability differs between women with first-onset post-partum psychosis and those with bipolar disorder more generally., Methods: In this case-control study on first-onset post-partum psychosis and bipolar disorder in the UK, we included 203 women with first-onset post-partum psychosis (defined as a manic, mixed, or psychotic depression episode within 6 weeks of delivery without a psychiatric history) and 1225 parous women with a history of bipolar disorder. Information on women with bipolar disorder was obtained from the Bipolar Disorder Research Network database, and participants were recruited through screening community mental health teams across the UK and via the media and patient support organisations. All were assessed using a semistructured face-to-face psychiatric interview and psychiatric case note review. 2809 women from the general population were recruited via the national UK Blood Services and the 1958 Birth Cohort (UK National Child Development Study) as controls and matched to cases according to genetic ancestry. All self-reported their ethnicity as White and were recruited from across the UK. Polygenic risk scores (PRSs) were generated from discovery genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Logistic regression was used to model the effect of each PRS on diagnosis, and the RRs and ORs presented were adjusted for ten principal components of genetic variation to account for population stratification., Findings: 203 women with first-onset post-partum psychosis (median age at interview: 46 years [IQR 37-55]) and 1225 women with bipolar disorder (49 years [41-58]) were recruited between September, 1991, and May, 2013, as well as 2809 controls. Women with first-onset post-partum psychosis had similar bipolar disorder and schizophrenia PRSs to women with bipolar disorder, which were significantly higher than those of controls. When compared with controls, women with first-onset post-partum psychosis had an adjusted relative risk ratio (RR) for bipolar disorder PRSs of 1·71 (95% CI 1·56-1·86, p<0·0001) and for schizophrenia PRSs of 1·82 (1·66-1·97, p<0·0001). The effect sizes were similar when comparing women with bipolar disorder to controls (adjusted RR 1·77 [1·69-1·84], p<0·0001 for bipolar disorder PRSs; 2·00 (1·92-2·08), p<0·0001 for schizophrenia PRSs). Although women with bipolar disorder also had higher major depression PRSs than did controls (1·24 [1·17-1·31], p<0·0001), women with first-onset post-partum psychosis did not differ from controls in their polygenic liability to major depression (0·97 (0·82-1·11), p=0·63)., Interpretation: Our study supports the recognition of first-onset post-partum psychosis as a separate nosological entity within the bipolar disorder spectrum both in research and clinical settings., Funding: Wellcome Trust and Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Women with bipolar disorder (BD) are at high risk of mania/psychosis following childbirth. The risk factors for these episodes remain poorly understood and prospective studies are rare. Here, we examine whether mood episodes occurring within pregnancy predict postpartum recurrence in women with BD using a prospective design., Method: 128 women with DSM-5 BD were followed from week 12 of pregnancy (baseline) to 12-weeks postpartum. Semi-structured interviews, supplemented by clinician questionnaires and case-note review, assessed lifetime psychiatric history at baseline, and perinatal psychopathology at two follow-up assessments: third-trimester of pregnancy and 12-weeks postpartum., Results: Postpartum follow-up data were obtained for 124/128 (97%) women [98 bipolar I disorder/schizoaffective-BD (BD-I/SA-BD group) and 26 bipolar II disorder/other specified BD and related disorder (BD-II/BD-OS group)]. Perinatal recurrence was high in both diagnostic groups (57% and 62% respectively). Women with BD-I/SA-BD were significantly more likely to experience mania/psychosis within 6 weeks postpartum (23%, n=22/96) compared to those with BD-II/BD-NOS (4%, n=1/25; p=0.042). In BD-I/SA-BD, mania/psychosis in pregnancy significantly elevated risk of mania/psychosis postpartum compared to remaining well (RR 7.0, p<0.001) and experiencing non-psychotic depression in pregnancy (RR 3.18, p=0.023) Limitations: Predominantly United Kingdom White sample and limited BD-II/BD-OS sample size., Conclusions: Women with BD are at high risk of recurrence during pregnancy and the postpartum. Over and above risk conferred by a history of BD-I/SA-BD, mania/psychosis during pregnancy further increased risk of postpartum mania/psychosis in this high-risk group. These data may have important implications for prediction and management of severe postpartum recurrence of BD., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Early-stage predictors of illness course are needed in bipolar disorder (BD). Differences among patients with a first depressive versus maniac/hypomanic episode have been stated, although in most studies, memory bias and time from onset to start of specialized treatment might interfere. The aim was to compare the first 10 years of illness course according to polarity at onset., Methods: 49 type I BD patients admitted for treatment for a first-time affective episode and a following 10-year attendance to the institution were included. A retrospective year by year comparison according to polarity at onset (depressive (DPO) or maniac (MPO)) was performed. Cramer's V and Cohen d were computed to determine effect size., Results: 59.2% (n = 29) started with MPO. Both groups were similar in demographic and social outcome characteristics, clinical features, and treatment variables. Patients with DPO reported more depressive episodes than MPO patients (U = 149.0 p < .001, Cohen's d = 0.87); both groups had a similar number of manic episodes. Only during the first year of follow-up, suicide attempts (SA) were more frequent in patients with DPO while the presence of a psychotic episode and psychiatric hospitalizations were more frequent in the MPO group., Conclusion: According to these findings, it can be concluded that illness onset is only indicative of depressive predominant polarity but is not related to other poor prognostic variables after the first year of illness onset, in treated BD. SA in the first year of an affective disorder could represent a marker of BD., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Aim: This study aimed to evaluate the prevalence of unipolar mania (UM) in a group of patients of bipolar disorder (BD). Additionally, effort was made to evaluate the demographic, clinical and treatment related factors, which distinguish subjects of UM from BD., Methodology: Seven hundred and seventy-three patients with BD, of at least 10 years duration, recruited from 14 General Hospital Units of tertiary care centers from India were evaluated for UM., Results: The prevalence of UM, varied from 5.4% to 20.3%, depending on the definition used. With the most stringent definition of ≥4 episodes of mania and at least 5 years of follow-up, the prevalence of UM was 5.4%. Compared to patients of BD, who have episodes other than mania too, those with UM had lower proportion of patients with lifetime history of suicide attempts, spent less time in the episodes in their lifetime and had lower severity of residual depressive and manic symptoms. Further, compared to those with episodes other than mania too, those with UM had higher number of manic episodes per year of illness, had higher proportion of patients who had more than five episodes in the lifetime and had higher proportion of those with at least one episode with psychotic symptoms in the lifetime., Conclusion: The present study suggests that a small proportion of patients with BD have UM course and this runs a different clinical course compared to that seen in patients with traditionally recognized as BD.

Objective: This study aimed to assess the clinical phenomenology and characteristics of prodromal symptoms in Chinese patients with bipolar disorder (BPD) prior to their index mood episode., Methods: Semi-structured interviews [Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R)] were administered to patients within 3 years of BPD (I and II) onset., Results: 120 stable inpatients and outpatients were included (65% males, mean age: 26.5±10.0 years). Feeling extremely energetic (61.8%), overly cheerful (49.1%), racing thoughts (48.2%), overly talkative (47.3%), and decreased need for sleep (43.6%) most frequently preceded the first (hypo)manic episode, whereas depressed mood (78.5%), tiredness (53.9%), reduction of enjoyment (52.3%), trouble concentrating (49.2%) and insomnia (47.7%) often occurred prior to the index depressive episode. The prevalence of anxiety or nervousness (p = 0.009), social isolation (p = 0.004), and losing temper (p < 0.001) differed significantly depending on the different episodes. Prior to any depressive episode, insomnia (p = 0.035) lasted significantly longer and sleeping too much (p = 0.033) was more severe, whereas oppositionality (p < 0.001), hallucinations (p = 0.024) and psychosis index score (p = 0.044) were more severe before any (hypo) manic episode. Furthermore, depressed mood (p = 0.006) was more frequent prior to depression, while anxiety or nervousness (p = 0.018), oppositionality (p = 0.001), and psychosis index score (p = 0.009) were more frequent before any (hypo) manic episode., Conclusions: Characteristic affective and psychotic symptoms, including depressed mood and subthreshold hypo (manic) symptoms occurred in the prodromal phase. The pre-depression prodromal symptoms lasted longer than the pre-(hypo) mania prodromal symptoms. Our findings indicated that identifying prodromal symptoms of BPD may be beneficial for early diagnosis and intervention before the development of full episodes., (Copyright © 2021. Published by Elsevier B.V.)

COVID19 infection was associated with possible psychiatric manifestations, including psychosis and mania. In addition, psychiatric disorders might be triggered by severe psychological reactions to the pandemic or the measures taken to contain it. This study aimed to assess the trends of new-onset psychosis/mania during the pandemic timeline. Psychiatric emergency department records during January-July 2019 and 2020 of two regional mental health centers were manually examined. Cases of new-onset psychosis or mania were found in 326 out of 5161 records examined. The ratio of these cases increased by 45.5% in 2020 compared to 2019 (189 out of 2367, 137 out of 2479, respectively, p = 0.001). The peak increase was in April 2020 (9.4% vs. 4.7%, p = 0.015). There was no association between the rise of new-onset psychotic or manic episodes and national incidence of COVID19 cases, as observed during Israel 2nd wave. PCR tests were negative, except a single case. In this study, an increase in new-onset psychosis/mania was identified during the initial phase of the pandemic. Though causality could not be directly inferred, lack of infection symptoms, negative PCR testing and temporal distribution incongruent with COVID19 caseload did not support a direct effect of SARS-CoV-2. Alternative explanations are discussed, such as psychological reaction to stress and preventive measures, as well as case-shifting between different mental health settings., (© 2021. The Author(s).)

Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56-7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73-10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk-for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Aim: The aim of the present study was to detect factors associated with duration of untreated illness (DUI) in bipolar disorder (BD)., Method: A total of 1575 patients were selected for the purposes of the study. Correlation analyses were performed to analyse the relation between DUI and quantitative variables. The length of DUI was compared between groups defined by qualitative variables through one-way analyses of variance or Kruskal-Wallis's tests according to the distribution of the variable. Linear multivariable regressions were used to find the most parsimonious set of variables independently associated with DUI: to this aim, qualitative variables were inserted with the numeric code of their classes by assuming a proportional effect moving from one class to another., Results: An inverse significant correlation between length of DUI and time between visits in euthymic patients was observed (r = -.52, P < .001). DUI resulted to be longer in patients with: at least one lifetime marriage/partnership (P = .009), a first psychiatric diagnosis of major depressive disorder or substance abuse (P < .001), a depressive polarity of first episode (P < .001), no lifetime psychotic symptoms (P < .001), BD type 2 (P < .001), more lifetime depressive/hypomanic episodes (P < .001), less lifetime manic episodes (P < .001), presence of suicide attempts (P = .004), depressive episodes (P < .001), hypomanic episodes (P = .004), hospitalizations (P = .011) in the last year., Conclusions: Different factors resulted to increase the length of DUI in a nationwide sample of bipolar patients. In addition, the DUI was found to show a negative long-term effect in terms of more suicidal behaviour, more probability of hospitalization and depressive/hypomanic episodes., (© 2020 John Wiley & Sons Australia, Ltd.)

Doxycycline has been hypothesized to prevent development of severe mental illness (SMI) through the suppression of microglia, especially if administered during the intense synaptic pruning period of adolescence. However, results from register studies on potential benefits differ considerably. The aim of the present study was to determine whether doxycycline exposure during adolescence is associated with reduced SMI risk, and to investigate if a direct and specific causality is plausible. This is a Swedish national population register-based cohort study of all individuals born from 1993 to 1997, followed from the age of 13 until end of study at the end of 2016. The primary exposure was cumulative doxycycline prescription ≥3000 mg and outcomes were first diagnosis of non-affective psychosis (F20-F29) and first diagnosis of bipolar disorder (F30-F31). Causal effects were explored through Cox regressions with relevant covariates and secondary analyses of multilevel exposure and comparison to other antibiotics. We found no association between doxycycline exposure and risk of subsequent non-affective psychosis (adjusted hazard ratio (HR) 1.15, 95% CI 0.73-1.81, p = 0.541) and an increased risk of subsequent bipolar disorder (adjusted HR 1.95, 95% CI 1.49-2.55, p < 0.001). We do not believe the association between doxycycline and bipolar disorder is causal as similar associations were observed for other common antibiotics., (© 2021. The Author(s).)

Objective: This study aimed to describe reports of psychiatric adverse drug reaction (ADR) in the spectrum of bipolar (manic features) or psychotic disorders that occurred under tumor necrosis factor alpha (TNF-α) inhibitors therapy., Methods: We searched the French pharmocovigilance database for reports of psychiatric ADR in the spectrum of bipolar (manic features) or psychotic disorders during treatment with TNF-α inhibitors. Psychiatric symptoms were divided in 2 categories: (i) confirmed diagnosis of manic episode or acute psychosis and (ii) psychiatric symptoms with psychotic or manic features but not meeting sufficient criteria for diagnosis of psychosis or manic disorder., Results: Overall, 9942 reports of ADR were registered in the French pharmacovigilance database with TNF-α inhibitors, including 243 reports of psychiatric ADR. Among them, we identified 41 reports of psychotic or manic disorders as define above: 9 characterised manic episodes and 32 psychiatric disorders with psychotic or manic features. TNF-α inhibitors were the only medication suspected in 23 reports (56%). The delay between starting TNF-α inhibitors treatment and onset of symptoms varied from hours to years with a median time of 40 days. Psychiatric symptoms improved in 22/23 patients in whom the TNF-α inhibitor was withdrawn., Conclusion: Depressive disorders are well-known ADR of TNF-α inhibitors, but we report, here, 41 reports of psychiatric ADR diagnosed as manic or psychotic disorders or in the spectrum of bipolar or psychotic disorders with these treatments. Epidemiological studies are needed to confirm this signal., (Copyright © 2020. Published by Elsevier Masson SAS.)