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Cognitive functioning heterogeneity is a well-recognized phenomenon in individuals diagnosed with mood disorders. Cognitive Reserve (CR) has been linked to multiple positive outcomes, including cognitive performance in these patients. This systematic review and meta-analysis aim to provide a comprehensive analysis of the relationship between CR and cognitive functioning in individuals with mood disorders, including bipolar disorder and depressive disorders. Following PRISMA guidelines, a systematic review and meta-analysis was conducted of original research exploring the relationship between CR and cognitive performance in adult individuals with mood disorders. The literature search was conducted on PubMed, Scopus, and Web of Science, from 2002 to September 2023, and the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. Overall, 17 studies met the inclusion criteria for the systematic review and 11 for the meta-analysis. Both qualitative and quantitative findings suggested a positive relationship between CR measures and cognitive domains. CR emerges as a possible protective factor for cognitive functioning in adult individuals with mood disorders, potentially helping to mitigate the cognitive impairments associated with the disorder. These findings underscore the importance of the fact that promoting and enhancing CR could help in the cognitive prognosis of this population., Competing Interests: Declaration of competing interest SA has been a consultant to and/or has received honoraria/grants from Otsuka-Lundbeck, with no financial or other relationship relevant to the subject of this article. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, BoehringerIngelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, SanofiAventis, Sunovion, Takeda, and Viatris, outside the submitted work. IB has received honoraria and travel support from Angelini and Lundbeck and grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III supported by ERDF Funds from the European Commission (PI18/0242/PI21/0391), National Drugs Plan, and Fundación Alicia Koplowitz. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Medincell, Merck, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. The rest of authors report no biomedical financial interests or potential conflicts of interest related to the present article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is a severe psychiatric disease and part of its burden is related to the high rates of lifetime psychiatric comorbidity (PC), with diagnostic, therapeutic, and prognostic implications., Methods: Registered in PROSPERO (CRD42021282356). Meta-analyses were performed, searching for relevant papers published from 1993 to 2022 in Medline/PubMed (including E-Pub Ahead of Print), Embase, Cochrane Library (Central), PsycINFO, Scopus, Web of Science and via hand-searching, without language restrictions. 12.698 studies were initially identified, 114 of which were ultimately chosen based on the eligibility criteria. We performed two meta-analyses (prevalence and risk ratio) of mental health conditions among subjects with BD and then conducted a comprehensive examination of moderator effects using multivariable meta-regression models for moderators identified as significant in the univariable analysis., Findings: Overall PC prevalence of at least one disorder was 38.91 % (95 % CI 35.24-42.70) and the most frequent disorders were: anxiety (40.4 % [34.97-46.06]), SUD (30.7 % [23.73-38.73]), ADHD (18.6 % [10.66-30.33]) and Disruptive, impulse-control and conduct disorder (15 % [6.21-31.84). The moderators with higher association with individual prevalences were UN's Human Development Index (HDI), female gender, age, suicide attempt, and age at onset (AAO)., Interpretation: It becomes evident that the prevalence of PC among individuals with BD is notably high, surpassing rates observed in the general population. This heightened prevalence persists despite significant heterogeneity across studies. Consequently, it is imperative to redirect clinical focus towards comprehensive mental health assessments, emphasizing personalized and routine screening. Additionally, there is a pressing need for the enhancement of public policies to create a supportive environment for individuals with BD, ensuring better therapeutic conditions and sustained assistance. By addressing these aspects, we can collectively strive towards fostering improved mental health outcomes for individuals with BD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Bipolar disorder (BD) is a major cause of disability-adjusted life years in young adults. Pregnancy complications have previously been associated with BD. The current study aimed to examine the association between perinatal factors and BD., Methods: We included 3,794 subjects from the 1993 Pelotas population-based birth cohort study. We assessed 27 variables at birth and modeled BD onset at 18 and 22 years. Bivariate analysis was performed by means of binomial logistic regression models. The variables with p-values less than 0.05 were included in a multiple regression with confounders., Results: Maternal smoking was associated with a 1.42-fold increased risk of BD at 18 or 22 years old (95%CI 1.091-1.841), and maternal passive exposure to tobacco with a 1.43-fold increased risk (95%CI 1.086-1.875). No association was found between other perinatal factors and BD after controlling for confounders., Conclusion: The results of the present cohort study corroborate previous reports in the literature indicating a negative effects of maternal smoking during pregnancy. These findings can be further tested and support the development of strategies to prevent the onset development of BD., Competing Interests: ICP receives authorship royalties from Springer Nature and ArtMed; has served as consultant, advisor, or continuing medical education speaker for Janssen, LundBeck, Libbs, Daiichi Sankyo, EMS, and Pfizer. The other authors report no conflicts of interest.

Objective: This study investigated the relationship between impulsivity and early trauma through a network analysis in individuals diagnosed with different substance use disorders., Methods: In a cross-sectional design, the sample included 556 men with substance use disorders (195 with alcohol use, 157 with cocaine/crack use, and 214 with polysubstance use). Early trauma and impulsive behavior were assessed using the Childhood Trauma Questionnaire and the Barratt Impulsiveness Scale, respectively. The connection between trauma and impulsivity was assessed using network analysis through a fused graphical lasso algorithm., Results: No connection was observed between impulsivity and trauma networks in individuals with alcohol use disorder. In those with cocaine use disorder, networks were linked through the motor domain and sexual abuse nodes. Inverse connections were observed between the emotional neglect node and perseverance, but not the non-planning node. In polysubstance use, the connection between impulsivity and trauma networks was weak, with the cognitive complexity node connecting to the trauma network through physical abuse. There connections were inversely proportional between the motor domain and emotional neglect nodes, as well as between cognitive instability and physical neglect., Conclusion: Our results suggest that the relationship between the type of early (childhood) trauma and the expression of impulsivity could lead to different substance use profiles., Competing Interests: The authors report no conflicts of interest.

Mood disorders significantly impact global health, with MDD ranking as the second leading cause of disability in the United States and BD ranking 18th. Despite their prevalence and impact, the relationship between premorbid intelligence and the subsequent development of BD and MDD remains inconclusive. This study investigates the potential of premorbid Intelligence Quotient (IQ) and school failure frequency as risk factors for Bipolar Disorder (BD) and Major Depressive Disorder (MDD) in a birth cohort setting. We analyze data from the Pelotas population-based birth cohort study, comprising 3580 participants aged 22, who had no prior mood disorder diagnoses. Utilizing regression models and accounting for potential confounders, we assess the impact of IQ and school failure, measured at age 18, on the emergence of BD and MDD diagnoses at age 22, using individuals without mood disorders as comparators. Results reveal that lower IQ (below 70) at 18 is associated with an increased risk of BD (Adjusted Odds Ratio [AOR] 1.75, 95%CI: 1.00-3.09, p < 0.05), while higher IQ (above 120) is linked to MDD (AOR 2.16, 95%CI: 1.24-3.75, p < 0.001). Moreover, an elevated number of school failures is associated with increased BD risk (AOR 1.23, 95%CI: 1.11-1.41, p < 0.001), particularly for BD type 1 (AOR 1.36, 95% CI: 1.17-1.58, p < 0.001). These findings offer insights into the distinct premorbid intellectual characteristics of BD and MDD and contribute to a deeper understanding of their developmental trajectories, potentially informing the development of risk assessment tools for mood disorders., Competing Interests: Declaration of competing interest Flávio Kapczinski reports personal fees from Daiichi Sankyo and Janssen-Cilag, grants from Stanley Medical Research Institute (07TGF/1148), grants from National Institute for Science and Technology (INCT - CNPq 465458/2014–9), and from the Canada Foundation for Innovation - CFI. Ives Cavalcante Passos has received research support from or served as consultant, adviser or speaker for Lundbeck, EMS, Libbs, and receives authorship royalties from Springer Nature and ArtMed. Furthermore, Ives Cavalcante Passos’ research is supported by National Council for Scientific and Technological Development (CNPq) and by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil Mauricio Kunz reports personal fees from Daiichi Sankyo. Francisco Diego Rabelo-da-Ponte receives authorship royalties from Springer Nature. Silvia Amoretti has been supported by a Sara Borrell contract (CD20/00177), funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Social Fund “Investing in your future”. The remaining authors do not have competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Despite previous literature, the superiority of Second-generation Antipsychotics (SGAs) relative to First-generation Antipsychotics- especially haloperidol - on cognitive management in schizophrenia is still controversial. Thus, we aimed to compare the effects of haloperidol versus SGAs on the cognitive performance of individuals with schizophrenia or related disorders., Methods: We conducted an updated systematic review and nine pairwise meta-analyses of double-blinded randomized controlled trials published up to October 30th, 2022, using Medline, Web of Science, and Embase., Results: Twenty-eight trials were included, enrolling 1,932 individuals. Compared to SGAs, haloperidol performed worse on cognitive composite (MD -0.13; 95% CI: -0.33 to -0.03; MD = mean difference, CI = confidence interval), processing speed (MD -0.17; 95% CI: -0.28 to -0.07), attention (MD -0.14; 95% CI: -0.26 to -0.02), motor performance (MD -0.17; 95% CI: -0.31 to -0.03), memory and verbal learning (MD -0.21; 95% CI: -0.35 to -0.08), and executive function (MD -0.27; 95% CI: -0.43 to -0.11). In contrast, there were no significant differences between SGAs and haloperidol on working memory (MD 0.10; 95% CI: -0.08 to 0.27), visual learning (MD 0.08; 95% CI: -0.05 to 0.21), social cognition (MD 0.29; 95% CI: -0.30 to 0.88), and visuoconstruction (MD 0.17; 95% CI: -0.04 to 0.39)., Conclusion: Haloperidol had poorer performance in global cognition and in some cognitive domains, but with small effect sizes. Therefore, it was not possible to conclude that haloperidol is certainly worse than SGAs in the long-term cognitive management of schizophrenia., Competing Interests: Maurício Kunz reports personal fees from Daiichi Sankyo and Janssen-Cilag. No other conflicts of interest declared concerning the publication of this article.

Background: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample., Methods: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001., Results: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger., Conclusion: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition., (© 2023. The Author(s).)

Objectives: Little is known about the relationship between depression in mothers and problematic gaming in their children. Therefore, we aimed to investigate the potential role of mothers' depression in childhood as a risk factor for problematic gaming in their offspring in late adolescence/young adulthood., Methods: We assessed data from 1557 participants on three waves (T0 collected in 2010/2011, T1 in 2013/2014, and T2 in 2018/2019) of a large Brazilian school-based cohort. Mother's depression at T0 was tested as a predictor of problematic gaming at T2 in a logistic regression model. In mediation analyses, we individually assessed internalizing or externalizing disorders at T1 as mediators in this association, with participants' sex being tested as a moderator in both models. Inverse probability weights were used to account for sample attrition at T2. All models were adjusted for maternal and participant-related covariates., Results: Mother's depression at T0 was significantly associated with problematic gaming at T2 (OR = 2.09, p < 0.001) even after adjusting for multiple confounding factors. The presence of any internalizing disorder at T1 was a partial mediator of this relationship, accounting for 8.18% (p = 0.032) of the total effect, while the presence of any externalizing disorder at T1 was not a significant mediator. Participants' sex was not a significant moderator in mediation models., Conclusions: These findings suggest mother's depression in childhood as a risk factor for problematic gaming in later developmental stages, which may be partially mediated by internalizing psychopathology., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The present study aims to identify pathways between psychiatric network symptoms and psychosocial functioning and their associated variables among functioning clusters in the general population. A cross-sectional web-based survey was administered in a total of 3,023 individuals in Brazil. The functioning clusters were derived by a previous study identifying three different groups based on the online Functioning Assessment Short Test. Networking analysis was fitted with all items of the Patient-Reported Outcomes Measurement Information System for depression and for anxiety (PROMIS) using the mixed graphical model. A decision tree model was used to identify the demographic and clinical characteristics of good and low functioning. A total of 926 (30.63%) subjects showed good functioning, 1,436 (47.50%) participants intermediate functioning, and 661 (21.86%) individuals low functioning. Anxiety and uneasy symptoms were the most important nodes for good and intermediate clusters but anxiety, feeling of failure, and depression were the most relevant symptoms for low functioning. The decision tree model was applied to identify variables capable to discriminate individuals with good and low functioning. The algorithm achieved balanced accuracy 0.75, sensitivity 0.87, specificity 0.63, positive predictive value 0.63 negative predictive value 0.87 (p<0.001), and an area under the curve of 0.83 (95%CI:0.79-0.86, p<0.01). Our results show that individuals who present psychological distress are more likely to experience poor functional status, suggesting that this subgroup should receive a more comprehensive psychiatric assessment and mental health care., Competing Interests: Declaration of competing interest Eduard Vieta has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, and Takeda. Josep Antoni Ramos-Quiroga was on the speakers’ bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogui, Lundbeck, Almirall, Braingaze, Sincrolab, Medice and Rubió in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogui, Bial, Medice and Eli-Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli-Lilly, Lundbeck, Janssen- Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious, and Rubió. Norma Verdolini has received financial support for CME activities and travel funds from the following entities (unrelated to the present work): Angelini, Janssen, Lundbeck, Otsuka. Marco Antonio Caldieraro has received grants from the following entities (unrelated to the present work): Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Janssen. The rest of authors report no biomedical financial interests or potential conflicts of interest related to the present article., (Copyright © 2022 Elsevier B.V. and ECNP. All rights reserved.)

Abstract: In much of the West, including Brazil, drug use has increased since social distancing began in response to the pandemic. Use of smoked and modified drugs, and their impacts on health, may contribute to aggravate the effects of the pandemic. However, studies on the relationship between use of smoked drugs and the new coronavirus are still scarce and have not received enough attention in global health recommendations. This paper aims to briefly review the relationship between use of smoked drugs and acute respiratory syndrome coronavirus 2 [SARS-CoV-2]. Recent studies also suggest that drug consumption increases the risk of contamination by SARS-CoV-2 and leads to worse prognosis, particularly consumption of drugs that affect lung function. Use of smoked drugs, especially tobacco, is strongly associated with lung diseases that are risk factors for contamination by SARS-CoV-2. It is essential to develop strategies based on specific characteristics of drug users and for mental health professionals to be included in strategic teams. It is also necessary to invest in information campaigns regarding risks and prevention of harm caused by smoked drugs as well as to design strategies that facilitate access to psychosocial treatment during the pandemic., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Introduction: Consumption of substances has been associated with cognitive impairment. The Mini Mental State Examination (MMSE) is an easy-to-apply screening tool used to assess cognitive functions., Objectives: To evaluate the cognitive performance of individuals with alcohol (AUD) and/or crack cocaine use disorder (CUD) and polysubstance use using the MMSE and to investigate the impact of substance use profile and the moderation effect of educational level on MMSE performance., Methods: Cross-sectional study with 508 adult male inpatients diagnosed with substance use disorders (245 with AUD, 85 with CUD, and 178 with polysubstance use). Cognitive performance was assessed using the MMSE scale (total and composite scores)., Results: Individuals with AUD had worse total MMSE scores and scored worse for all three MMSE components compared to individuals with polysubstance use (p < 0.001, oral/written language comprehension, p < 0.001, attention/memory, and p = 0.007, motor functions). MMSE scores were positively correlated with educational level (p < 0.017), but were not associated with age, recent drug use, or years of drug use. Educational level moderated the impact of substance use on MMSE performance, especially total score and composite language comprehension score. Individuals with a low educational level (≤ 8 years) had worse performance than those with a high educational level (≥ 9 years), mainly in individuals with AUD (p < 0.001)., Discussion: Individuals with a low educational level and alcohol use are more prone to present cognitive impairment than crack cocaine users, especially involving language aspects. Better-preserved cognitive function could impact treatment adherence and might guide the decision of therapeutic strategies., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Background: Perinatal and prenatal risk factors may be implicated in the development of bipolar disorder, but literature lacks a comprehensive account of possible associations., Methods: We performed a systematic review and meta-analyses of observational studies detailing the association between prenatal and perinatal risk factors and bipolar disorder in adulthood by searching PubMed, Embase, Web of Science and Psycinfo for articles published in any language between January 1st, 1960 and September 20th, 2021. Meta-analyses were performed when risk factors were available in at least two studies., Findings: Twenty seven studies were included with 18 prenatal or perinatal factors reported across the literature. Peripartum asphyxia (k = 5, OR = 1.46 [1.02; 2.11]), maternal stress during pregnancy (k = 2, OR = 12.00 [3.30; 43.59]), obstetric complications (k = 6, OR = 1.41 [1.18; 1.69]), and birth weight less than 2500 g (k = 5, OR = 1.28 [1.04; 1.56]) were associated with an increased risk for bipolar disorder., Interpretation: Perinatal and prenatal risk factors are implicated in the pathogenesis of bipolar disorder, supporting a role of prenatal care in preventing the condition., Competing Interests: Declaration of interest ICP has received research support from or served as consultant, adviser or speaker for Lundbeck, EMS, Libbs, and receives authorship royalties from Springer Nature and ArtMed. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic has caused major disruptions in all aspects of daily functioning, from school and work to interactions with friends and family. The Functioning Assessment Short Test (FAST) is an interviewer-administered scale validated in the psychiatric sample with no previous study assessing its validity and reliability in a digital format. Thus, we aimed to analyse the psychometric properties of the digital version of the FAST and understand the implications of COVID-19 and restrictive measures on functioning., Methods: Data were collected using an online survey. The psychometric properties of the digital FAST were assessed by confirmatory factor analysis, Cronbach's alpha, and discriminant functional by cluster analysis in a community sample., Results: Out of the total sample, 2,543 (84.1%) were female, and the mean (SD) age was 34.28 (12.46) years. The digital FAST retained the six factors structure observed in the original version, with Cronbach's alpha above 0.9. In addition, we showed evidence of discriminant validity by differentiating three clusters of psychosocial functioning. Clinical and demographic differences between groups explained, in part, the heterogeneity of functioning, thus providing support for the construct validity of the instrument., Conclusion: The digital FAST is a simple and easy-to-understand instrument that provides a multidimensional assessment of functioning without the need for an interviewer. Furthermore, our findings may help to better understand the psychosocial implications of the pandemic and the importance of planning specific interventions to rehabilitee the affected group., Competing Interests: E.V. has received grants and served as a consultant, advisor or CME speaker unrelated to this work for the following entities: AB-Biotics, Abbvie, Angelini, Dainippon Sumitomo Pharma, Ferrer, GH Research, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda. The other authors do not declare any conflict of interest related to this manuscript., (© 2022 Serafim et al.)

Background: Schizophrenia (SZ) is a complex brain disorder linked to cognitive and neurostructural abnormalities that involves genetic and environmental factors with obstetric complications (OCs) at birth conferring a high risk for the disease. Indeed, current research in the general population describes the deleterious effect of OCs on cognitive performance in adulthood. With this rationale, we aim to review the relationship between OCs and cognition in SZ and related psychotic disorders., Methods: A systematic review and meta-analysis describing cognitive function and OCs in patients with SZ and related disorders were conducted. PubMed, EmBase, SCOPUS, and the Cochrane Library were systematically searched to identify eligible studies up to January 2022. We calculated the effect sizes (Hedges' g) of cognitive domains within each study and quantified the proportion of between-study variability using the I 2 statistic. Homogeneity was assessed using the Q -statistic ( X 2 ). The study was registered on PROSPERO (CRD42018094238)., Results: A total of 4124 studies were retrieved, with 10 studies meeting inclusion criteria for the systematic review and eight for meta-analysis. SZ subjects with OCs showed poor verbal memory [Hedges' g = -0.89 (95% CI -1.41 to -0.37), p < 0.001] and working memory performance [Hedges' g = -1.47 (95% CI -2.89 to -0.06), p = 0.01] in a random-effect model compared to those without OCs., Conclusions: OCs appear to have a moderate impact on specific cognitive such as working memory and verbal memory. Our findings suggest that OCs are associated with brain development and might underlie the cognitive abnormalities described at onset of psychosis.

Objective: To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR)., Methods: The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis., Results: BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; β = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; β = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; β = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA., Conclusion: Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth., Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer., Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001)., Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Subjects with bipolar disorder (BD) show heterogeneous cognitive profile and that not necessarily the disease will lead to unfavorable clinical outcomes. We aimed to identify clinical markers of severity among cognitive clusters in individuals with BD through data-driven methods., Methods: We recruited 167 outpatients with BD and 100 unaffected volunteers from Brazil and Spain that underwent a neuropsychological assessment. Cognitive functions assessed were inhibitory control, processing speed, cognitive flexibility, verbal fluency, working memory, short- and long-term verbal memory. We performed hierarchical cluster analysis and discriminant function analysis to determine and confirm cognitive clusters, respectively. Then, we used classification and regression tree (CART) algorithm to determine clinical and sociodemographic variables of the previously defined cognitive clusters., Results: We identified three neuropsychological subgroups in individuals with BD: intact (35.3%), selectively impaired (34.7%), and severely impaired individuals (29.9%). The most important predictors of cognitive subgroups were years of education, the number of hospitalizations, and age, respectively. The model with CART algorithm showed sensitivity 45.8%, specificity 78.4%, balanced accuracy 62.1%, and the area under the ROC curve was 0.61. Of 10 attributes included in the model, only three variables were able to separate cognitive clusters in BD individuals: years of education, number of hospitalizations, and age., Conclusion: These results corroborate with recent findings of neuropsychological heterogeneity in BD, and suggest an overlapping between premorbid and morbid aspects that influence distinct cognitive courses of the disease.

Background: Population heterogeneity and the lack of clinical and sociodemographic information in transgender individuals with gender dysphoria (GD) remains a challenge for specialized services in mental health and surgical procedures. It aimed to identify and describe profiles in a sample waiting for gender-affirming surgery., Methods: A sample of 100 outpatients with GD was assessed through a structured interview, Emotion Regulation Difficulty Scale (DERS), Ruminative Response Scale (RRS), Depression, Anxiety and Stress Scale (DASS-21) and Life Satisfaction scale (SWLS). Cluster analysis was used to identify different profile categories., Results: Two subgroups with different profiles were identified: with less clinical severity (LCS) and with high clinical severity (HCS) on emotional dysregulation, acute symptoms of depression, anxiety, stress and association with mental rumination. The HCS cluster had greater vulnerability in terms of psychiatric history, use of psychotropic drugs, HIV positive, child abuse and suicidal behavior., Conclusion: Different profiles were found regarding the vulnerability to mental health in a sample of transgender people with GD who seek a public hospital service for the same clinical-surgical objective. Longitudinal studies are essential to monitor the impact of these contrasts and to target personalized therapeutic approaches in the prevention of psychiatric disorders., (© 2022. The Author(s).)

Objective: Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders., Methods: A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition., Results: In the Cox regression model, ethnicity (white) (hazard ratio [HR] 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05)., Conclusions: These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.

Impairments in a broad range of cognitive domains have been consistently reported in some individuals with first-episode psychosis (FEP). Cognitive deficits can be observed during the prodromal stage. However, the course of cognitive deficits is still unclear. The aim of this study was to identify cognitive subgroups over time and to compare their sociodemographic, clinical and functional profiles. A total of 114 patients with Schizophrenia Spectrum Disorders were included in the present study. We assessed subjects through psychiatric scales and eight neuropsychological tests at baseline and at two-year follow-up visit. We performed the Partition Around Medoids algorithm with all cognitive variables. Furthermore, we performed a logistic regression to identify the predictors related to the different cognitive clusters at follow-up. Two distinct subgroups were found: the first cluster characterized by cognitive impairment and a second cluster had relatively intact cognition in comparison with norms. Up to 54.7% of patients with cognitive deficits at baseline tended to improve during the first two years of treatment. Patients with intact cognition at follow-up had a higher socioeconomic status, later age of onset, lower negative symptoms and a higher cognitive reserve (CR) at baseline. CR and age of onset were the baseline variables that predicted cognitive impairment. This research allows us to obtain a better understanding of the heterogeneous profile of psychotic disorders. Identifying the characteristics of patients who will present a cognitive impairment could improve early detection and intervention. These results suggest that enhancing CR could contribute to improving the course of the illness., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Identifying the profile of risky behaviors among drivers is central to propose effective interventions. Due to the multidimensional and overlapping aspects of risky driving behaviors, cluster analysis can provide additional insights in order to identify specific subgroups of risk. This study aimed to identify clusters of driving risk behavior (DRB) among car drivers, and to verify intra-cluster differences concerning clinical and sociodemographic variables. We approached a total of 12,231 drivers and we included 6392 car drivers. A cluster algorithm was used to identify groups of car drivers in relation to the DRB: driving without a seat belt (SB), exceeding the speed limit (SPD), using a cell phone while driving (CELL), and driving after drinking alcohol (DUI). The algorithm classified drivers within five different DRB profiles. In cluster 1 (20.1%), subjects with a history of CELL. In cluster 2 (41.4%), drivers presented no DRB. In cluster 3 (9.3%), all drivers presented SPD. In cluster 4 (12.5%), drivers presented all DRB. In cluster 5 (16.6%), all drivers presented DUI. Clusters with DUI-related offenses (4 and 5) comprised more men (81.9 and 78.8%, respectively) than the overall sample (63.4%), with more binge drinking (50.9 and 45.7%) and drug use in the previous year (13.5 and 8.6%). Cluster 1 had a high years of education (14.4 ± 3.4) and the highest personal income (Md = 3000 IQR [2000-5000]). Cluster 2 had older drivers (46.6 ± 15), and fewer bingers (10.9%). Cluster 4 had the youngest drivers (34.4 ± 11.4) of all groups. Besides reinforcing previous literature data, our study identified five unprecedented clusters with different profiles of drivers regarding DRB. We identified an original and heterogeneous group of drivers with only CELL misuse, as well as other significant differences among clusters. Hence, our findings show that targeted interventions must be developed for each subgroup in order to effectively produce safe behavior in traffic., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries., Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries)., Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01., Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed., (© 2021. The Author(s).)

Cognitive deficits are a core aspect of psychotic disorders; however, it is not clear to which extent different pharmacological treatments could distinctly impact these outcomes. Hence, we conducted a systematic review and ten network meta-analyses of randomized controlled trials to compare the effect of antipsychotics on cognitive performance of individuals with psychotic disorders. Fifty-four trials were included in the analyses, enrolling 5866 patients. Compared to other antipsychotics, amisulpride performed better on verbal learning; quetiapine on composite score, attention and verbal learning; lurasidone on composite score; olanzapine on composite score and most cognitive domains; perphenazine on composite score, executive function, working memory, and verbal learning; risperidone on executive function and verbal learning; sertindole on processing speed; and ziprasidone on composite score, working memory, and verbal learning. Oppositely, haloperidol performed poorer on all cognitive domains, occupying the last positions in all rankings; and clozapine performed poorer on composite score, executive function, verbal learning, and visuoconstruction. We hope that these results should be taken into account when assessing and treating individuals with psychosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Schizophrenia (SZ) is a chronic debilitating disease. Subjects with SZ have significant shorter life expectancy. Growing evidence suggests that a process of pathological accelerated aging occurs in SZ, leading to early development of severe clinical diseases and worse morbimortality. Furthermore, unaffected relatives can share certain endophenotypes with subjects with SZ. We aim to characterize accelerated aging as a possible endophenotype of schizophrenia by using a machine learning (ML) model of peripheral biomarkers to accurately differentiate subjects with SZ (n = 35), their unaffected siblings (SB, n = 36) and healthy controls (HC, n = 47). We used a random forest algorithm that included biomarkers related to aging: eotaxins CCL-11 and CCL-24; the oxidative stress markers thiobarbituric acid-reactive substances (TBARS), protein carbonyl content (PCC), glutathione peroxidase (GPx); and telomere length (TL). The ML algorithm of biomarkers was able to distinguish individuals with SZ from HC with prediction accuracy of 79.7%, SZ from SB with 62.5% accuracy and SB from HC with 75.5% accuracy. These results support the hypothesis that a pathological accelerated aging might occur in SZ, and this pathological aging could be an endophenotype of the disease, once this profile was also observed in SB, suggesting that SB might suffer from an accelerated aging in some level., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Stigmatizing attitudes against individuals diagnosed with mental illness could increase the severity of psychiatric symptoms, lead to delay in getting medical support, and decrease adherence to treatments. Identifying the groups most associated with stigmatization could orientate actions to reduce this prejudice and improve patients' prognosis., Objective: To investigate variables associated with stigmatization toward psychiatric disorders in Brazil., Methods: A Web-based survey was sent out to assess the sociodemographic characteristics of the respondents and their perception of mental illness. Included participants were composed of Brazilians aged 18 years or over, with access to the internet and social networks. The questionnaire was available from June to August 2018 on Facebook., Results: A total of 2414 respondents were included. The majority were female, white, aged between 18 and 29 years, and had more than 10 years of study. The variables associated with stigma were male sex, fewer years of education, lower household income, the presence of a psychiatric disorder in a first-degree relative, and internalized stigma., Conclusions: The present study identified variables associated with the stigma against psychiatric disorders. Future studies should propose intervention strategies, such as to foster education about mental illness and to promote the importance of seeking help from a mental health professional, to address this problem in Brazil., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The extreme variability in symptom presentation reveals that individuals diagnosed with a first-episode psychosis (FEP) may encompass different sub-populations with potentially different illness courses and, hence, different treatment needs. Previous studies have shown that sociodemographic and family environment factors are associated with more unfavorable symptom trajectories. The aim of this study was to examine the dimensional structure of symptoms and to identify individuals' trajectories at early stage of illness and potential risk factors associated with poor outcomes at follow-up in non-affective FEP. One hundred and forty-four non-affective FEP patients were assessed at baseline and at 2-year follow-up. A Principal component analysis has been conducted to identify dimensions, then an unsupervised machine learning technique (fuzzy clustering) was performed to identify clinical subgroups of patients. Six symptom factors were extracted (positive, negative, depressive, anxiety, disorganization and somatic/cognitive). Three distinct clinical clusters were determined at baseline: mild; negative and moderate; and positive and severe symptoms, and five at follow-up: minimal; mild; moderate; negative and depressive; and severe symptoms. Receiving a low-dose antipsychotic, having a more severe depressive symptomatology and a positive family history for psychiatric disorders were risk factors for poor recovery, whilst having a high cognitive reserve and better premorbid adjustment may confer a better prognosis. The current study provided a better understanding of the heterogeneous profile of FEP. Early identification of patients who could likely present poor outcomes may be an initial step for the development of targeted interventions to improve illness trajectories and preserve psychosocial functioning., Competing Interests: Conflict of interest E. Vieta has received research support from or served as consultant, adviser or speaker for AB-Biotics, Actavis, Allergan, Angelini, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, Telefónica, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC), and the Stanley Medical Research Institute, unrelated to the present work. M. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Lundbeck, Otsuka, Menarini and Takeda. C. De-la-Camara received financial support to attend scientific meetings from Janssen-Cilag, Almirall, Eli Lilly, Lundbeck, Rovi, Esteve, Novartis, and Astrazeneca M. Gómez-Ramiro reports grants from INSTITUTO CARLOS III, grants from ADAMED, non-financial support from JANSSENCILAG, non-financial support from LUNDBECK-OTSUKA, non-financial support from PFIZER, non-financial support from ANGELINI, outside the submitted work. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini. The rest of authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: Resilience is a process that allows recovery from or adaptation to adversities. The aim of this study was to evaluate state resilience during the COVID-19 pandemic in psychiatric patients (PP), unaffected relatives (UR) and community controls (CC)., Methods: This study is part of the Barcelona ResIlience Survey for Mental Health COVID-19 (BRIS-MHC) project. Logistic regression models were performed to identify mental health outcomes associated with bad state resilience and predictors of good state resilience. The association between state resilience and specific affective temperaments as well as their influence on the association between depressive symptoms and state resilience were verified., Results: The study recruited 898 participants that took part in the survey. The presence of depressive symptoms was a predictor of bad state resilience in PP (β=0.110, OR=1.117, p=0.028). No specific mental health outcome was associated with bad state resilience in UR and CC. Predictors of good state resilience in PP were having pursued hobbies/conducted home tasks (β=1.261, OR=3.528, p=0.044) and level of organization in the family (β=0.986, OR=2.682, p=0.008). Having a controlling family was inversely associated with good state resilience in CC (β=-1.004, OR=0.367, p=0.012). The association between bad state resilience and depressive symptoms was partially mediated by affective temperaments., Limitations: Participants self-reported their psychiatric diagnoses, their relatives' diagnoses or the absence of a psychiatric disorder, as well as their psychiatric symptoms., Conclusions: Enhancing resilience and coping strategies in the face of the COVID-19 pandemic might have important implications in terms of mental health outcomes., (Copyright © 2021. Published by Elsevier B.V.)

Objective: We set forth to build a prediction model of individuals who would develop bipolar disorder (BD) using machine learning techniques in a large birth cohort., Methods: A total of 3748 subjects were studied at birth, 11, 15, 18, and 22 years of age in a community birth cohort. We used the elastic net algorithm with 10-fold cross-validation to predict which individuals would develop BD at endpoint (22 years) at each follow-up visit before diagnosis (from birth up to 18 years). Afterward, we used the best model to calculate the subgroups of subjects at higher and lower risk of developing BD and analyzed the clinical differences among them., Results: A total of 107 (2.8%) individuals within the cohort presented with BD type I, 26 (0.6%) with BD type II, and 87 (2.3%) with BD not otherwise specified. Frequency of female individuals was 58.82% (n = 150) in the BD sample and 53.02% (n = 1868) among the unaffected population. The model with variables assessed at the 18-year follow-up visit achieved the best performance: AUC 0.82 (CI 0.75-0.88), balanced accuracy 0.75, sensitivity 0.72, and specificity 0.77. The most important variables to detect BD at the 18-year follow-up visit were suicide risk, generalized anxiety disorder, parental physical abuse, and financial problems. Additionally, the high-risk subgroup of BD showed a high frequency of drug use and depressive symptoms., Conclusions: We developed a risk calculator for BD incorporating both demographic and clinical variables from a 22-year birth cohort. Our findings support previous studies in high-risk samples showing the significance of suicide risk and generalized anxiety disorder prior to the onset of BD, and highlight the role of social factors and adverse life events., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Point-of-collection testing (POCT) devices for psychoactive substance detection through oral fluid samples are used in several countries for traffic enforcement. However, the reported reliability of such devices is quite heterogeneous among studies, and evaluating and comparing their analytical performance is of paramount importance to guide enforcement policies., Aim: To evaluate the analytical reliability of four POCT devices for the detection of cocaine and cannabinoids using oral fluid samples of Brazilian drivers., Method: A total of 168 drivers were recruited during standard roadblockfI procedures in Southern Brazil. Subjects were screened using one of the following POCT devices: the DDS2™, the DOA MultiScreen™, the Dräger Drug Test 5000™ and the Multi-Drug Multi-Line Twist Screen Device™ (MDML). Results of the screening tests were compared with chromatographic analyses in order to obtain the reliability parameters., Results: The prevalence of confirmed positive samples for cocaine and cannabinoids were 9 % and 4.4 %, respectively. For cocaine, three POCT devices (MDML™, Dräger DrugTest 5000™, DOA MultiScreen™) showed good reliability, greater than 80 % of performance measures, using guidelines for research on drugged driving published by Walsh et al. (cutoff 10ng/mL). However, for cannabinoids, the devices had low reliability-only Dräger DrugTest 5000™ had good performance using cut-offs proposed by Walsh et al. (cutoff 2ng/mL)., Conclusion: We observed a high prevalence of drivers testing positive for cocaine and cannabinoids. Most devices achieved good reliability performance for cocaine detection using cutoffs proposed by Walsh et al. or using the device's own cutoff. Instead, the reliability for cannabinoid detection obtained the desired parameters in just one device using cut-offs proposed by Walsh et al. and its own cutoff. Difficulties in detecting cannabinoids at the roadside should be better evaluated before the implementation of such tests., (Copyright © 2020. Published by Elsevier B.V.)

Background: Suicide is a severe health problem, with high rates in individuals with addiction. Considering the lack of studies exploring suicide predictors in this population, we aimed to investigate factors associated with attempted suicide in inpatients diagnosed with cocaine use disorder using two analytical approaches., Methods: This is a cross-sectional study using a secondary database with 247 men and 442 women hospitalized for cocaine use disorder. Clinical assessment included the Addiction Severity Index, the Childhood Trauma Questionnaire, and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, totalling 58 variables. Descriptive Poisson regression and predictive Random Forest algorithm were used complementarily to estimate prevalence ratios and to build prediction models, respectively. All analyses were stratified by gender., Results: The prevalence of attempted suicide was 34% for men and 50% for women. In both genders, depression (PRM = 1.56, PRW = 1.27) and hallucinations (PRM = 1.80, PRW = 1.39) were factors associated with attempted suicide. Other specific factors were found for men and women, such as childhood trauma, aggression, and drug use severity. The men's predictive model had prediction statistics of AUC = 0.68, Acc. = 0.66, Sens. = 0.82, Spec. = 0.50, PPV = 0.47 and NPV = 0.84. This model identified several variables as important predictors, mainly related to drug use severity. The women's model had higher predictive power (AUC = 0.73 and all other statistics were equal to 0.71) and was parsimonious., Conclusions: Our findings indicate that attempted suicide is associated with depression, hallucinations and childhood trauma in both genders. Also, it suggests that severity of drug use may be a moderator between predictors and suicide among men, while psychiatric issues shown to be more important for women., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate whether exposing rats to individual or combined environmental stressors triggers endophenotypes related to mood and anxiety disorders, and whether this effect depends on the nature of the behavior (i.e., innate or learned)., Methods: We conducted a three-phase experimental protocol. In phase I (baseline), animals subjected to mixed schedule of reinforcement were trained to press a lever with a fixed interval of 1 minute and a limited hold of 3 seconds. On the last day of phase I, an open-field test was performed and the animals were divided into four experimental groups (n=8/group). In phase II (repeated stress), each group was exposed to either hot air blast (HAB), paradoxical sleep deprivation (PSD) or both (HAB+PSD group) on alternate days over a 10-day period. Control group animals were not exposed to stressors. In phase III (post-stress evaluation), behavior was analyzed on the first (short-term effects), third (mid-term effects), and fifth (long-term effects) days after repeated stress., Results: The PSD group presented operant hyperactivity, the HAB group presented spontaneous hypoactivity and anxiety, and the HAB+PSD group presented spontaneous hyperactivity, operant hypoactivity, impulsivity, loss of interest, and cognitive impairment., Conclusion: A combination of environmental stressors (HAB and PSD) may induce endophenotypes related to bipolar disorder.

Maltreatments in childhood may have implications for neurodevelopment that could remain throughout life. Childhood trauma seems to be associated with the onset of bipolar disorder (BD), and its occurrence might accentuate the overall disease impairments related to cognitive deficits in BD. We aimed to evaluate the effects of a history of childhood trauma to estimated intellectual functioning (IQ) of individuals with BD. We included 72 subjects with BD during euthymia. Participants underwent a clinical interview and were assessed through the Childhood Trauma Questionnaire (CTQ) and Wechsler Abbreviated Scale of Intelligence (WASI). Most prevalent trauma subtypes were emotional abuse and neglect (54.1%). A linear regression model that included perceived childhood trauma, family history of severe mental disorders, age at diagnosis and psychotic symptoms during the first episode as main factors showed that only childhood trauma had a significant effect in predicting estimated IQ. Therefore, the history of childhood trauma in individuals with BD may play a role in intellectual development, suggesting that adversities during development result in decreased general cognitive abilities. These results reinforce the need to promote early interventions to protect childhood and to promote the well-being of children, contributing to the growth of healthy adults., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Evidence has shown heterogeneity of cognitive function among patients with bipolar disorder (BD). Our study aims to replicate recent findings of cognitive subgroups, as well as we assessed subjective cognitive difficulties and functioning in each cluster., Methods: Hierarchical cluster analysis was conducted to examine whether there were distinct neurocognitive subgroups based on neurocognitive battery. Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and Functioning Assessment Short Test (FAST) were used to assess subjective cognitive difficulties and functional impairment., Results: We found three distinct subgroups: a first cluster with intact cognition (n = 30, 43.5%), a second cluster with selective cognitive impairment (n = 23, 33.3%), and a third cluster with globally cognitive impairment (n = 16, 23.3%). The intact group had more years of education (p < .001) and higher estimated IQ (p < .001) than globally and selectively impaired subgroups. Additionally, they were younger (p = .011), had an earlier age at bipolar diagnosis (p < .037) and earlier age of first hospitalization (p < .035) compared to individuals with globally cognitive impairment., Limitations: This is a cross-sectional design with a small sample including only patients from a tertiary hospital., Conclusion: Our results give support to the existence of a continuum of severity from patients without impairment to those with poor cognitive functioning. Patients in the intact group seem to have higher cognitive reserve than other two groups. However, they also experienced cognitive complaints and some degree of functional impairment. These findings suggest the importance of using a combo of instruments (e.g., objective and subjective cognitive measures plus functioning instruments) for a complete assessment of patients with BD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

[This corrects the article DOI: 10.1371/journal.pone.0204820.].

Background: The present study analyzes the feasibility of text classification to predict individual suicidal behavior. Entries from Virginia Woolf's diaries and letters were used to assess whether a text classification algorithm could identify written patterns associated with suicide., Methods: This is a text classification study. We compared 46 text entries from the two months before Virginia Woolf's suicide with 54 texts randomly selected from Virginia Woolf's work during other periods of her life. Letters and diaries were included, while books, novels, short stories, and article fragments were excluded. The data was analyzed using a Naïve-Bayes machine-learning algorithm., Results: The model showed a balanced accuracy of 80.45%, sensitivity of 69%, and specificity of 91%. The Kappa statistic was 0.6, which means a good agreement, and the p-value of the model was 0.003. The area under the ROC curve (AUC) was 0.80. In other words, the model exhibited good performance when used for classifying Virginia Woolf's diaries and letters., Discussion: The present study showed the feasibility of a machine-learning model coupled with text to identify individual written patterns associated with suicidal behavior. Our text signature was able to identify the period of two months preceding suicide with a high accuracy. This technique may be applied to subjects with psychiatric disorders by means of data captured from social media, e-mail, among others. The algorithm may then predict a specific outcome and enable early intervention by clinicians., Competing Interests: The authors have declared that no competing interests exist.

Background: Verbal memory impairment may be considered an endophenotype in schizophrenia (SZ), also affecting the siblings of SZ subjects. Furthermore, the immune-inflammatory system response has an important modulatory effect on brain processes, especially on memory circuits., Objective: Investigating the relationship between TNF-α and IL-6 and memory performance in patients with SZ, their unaffected siblings (SB) and healthy controls (HC)., Methods: 35 subjects with SZ, 36 SB, and 47 HC underwent a neurocognitive assessment for verbal memory by means of the revised Hopkins Verbal Learning Test (HVLT-R) in addition to serum cytokines analyses., Results: SZ patients performed worse in HVLT-R than SB and HC, but SB and HC were not different. Regarding the biomarker levels, we found significant results of TNF-α for both groups. However, we did not find differences between groups after multiple-comparisons analysis. There were no significant correlations between episodic verbal memory, TNF-α, and IL-6., Conclusion: The results are compatible with the hypothesis that deficits in verbal memory of individuals with SZ could be secondary to inadequate functioning of cognitive processing areas, such as proactive cognitive control., (© 2018 S. Karger AG, Basel.)