OBJECTIVE:Understanding the molecular mechanisms of autism spectrum disorder (ASD) and its psychiatric comorbidities, including bipolar disorder (BD), is pivotal for uncovering pathways that shape neurodevelopmental trajectories and clinical heterogeneity. We aimed to identify ASD-specific gene-expression signatures and disrupted biological processes in prefrontal cortex, contrasting them with those observed in BD. METHODS:We performed a comparative transcriptomic analysis of RNA-seq datasets from postmortem prefrontal cortex samples of individuals with ASD or BD and controls. Differential expression was assessed with DESeq2, including batch as a covariate in the BD model. Functional interpretation used Gene Ontology over-representation analysis, KEGG Gene Set Enrichment Analysis and gene-concept network visualization. RESULTS:ASD samples showed 45 differentially expressed genes (DEGs), mainly downregulated non-coding RNAs, particularly small nuclear RNAs and small nucleolar RNAs. Enrichment analysis indicated a convergent profile related to RNA processing, spliceosome assembly and spliceosomal activity. In contrast, BD showed 12 candidate DEGs, mostly upregulated protein-coding genes. BD enrichment involved metal ion response and detoxification, amine and peptide hormone responses, vascular regulation and hydrolase activity, with genes associated with neuroinflammation such as SERPINA3 and CHI3L1 contributing to this profile. No shared DEGs or enriched GO Biological Process terms were observed between ASD and BD. CONCLUSION:These results support transcriptomic divergence in the prefrontal cortex, with ASD characterized by spliceosomal dysregulation, contrasting with metal ion response, vascular regulation and inflammation-associated signals in BD. Our findings provide a transcriptomic framework for future studies investigating disorder-specific molecular mechanisms and candidate signatures in ASD and BD.

As mudanças climáticas configuram uma ameaça imediata e crescente à saúde global, comsendo descritas como o maior desafio sanitário do século XXI. Seus impactos abrangem desde ondas de calor, desastres ambientais e insegurança hídrica e alimentar até a intensificação de doenças infecciosas e não transmissíveis. Estima-se que mais de 3,6 bilhões de pessoas vivam em condições de alta vulnerabilidade climática, especialmente em países de baixa e média renda, perpetuando desigualdades históricas.

Abstract Background Boredom is an aversive state commonly elicited by monotonous or insufficiently engaging situations. Mind-wandering has been proposed as one possible response to boredom, but the association between these phenomena may vary with depressive symptom severity, particularly when mind-wandering is habitual, excessive, or poorly regulated. We therefore examined whether depressive symptom severity moderates the association between state boredom and habitual excessive mind-wandering in psychiatric patients. Methods This cross-sectional study examined self-reported state boredom, depressive symptoms, and habitual excessive mind-wandering in 94 psychiatric outpatients spanning multiple diagnostic categories and age groups. Results Depressive symptom severity was reliably associated with state boredom across diagnostic categories (R P =0.623, p < 0.001). In addition, when studying the moderating effects of depressive symptom severity on the association between boredom and excessive mind-wandering, we observed a positive association of boredom and mind-wandering that progressively weakened with increasing degrees of depression (interaction of depression and boredom: β=−0.184, p = 0.039, ΔR 2 = 0.033). Conclusions Our findings indicate a robust correlation of state boredom and depression in various mental health disorders. Moreover, higher severity of individual depressive symptoms is associated with an attenuation of the coupling between state boredom and excessive mind-wandering tendencies. Replication in larger and more homogeneous samples is required to determine the generalizability of these observations. Trial registration Not applicable.

La consommation de drogues psychoactives constitue un problème majeur de santé publique au Brésil. Le présent article a pour objectif de synthétiser et de discuter le panorama de l’usage de substances licites et illicites dans le pays. Il s’agit d’une revue narrative fondée sur des données secondaires, dont la principale source est la IIIe enquête nationale sur l’usage de drogues par la population brésilienne, complétée par la littérature nationale et internationale existante sur le sujet. Les données indiquent que l’alcool est la substance la plus consommée (43,1 % au cours des 12 derniers mois), avec une prévalence similaire à la moyenne mondiale. La consommation de cigarettes se distingue par une diminution marquée au cours des dernières décennies, avec une prévalence actuelle de 17,3 % au cours des 12 derniers mois. Parmi les drogues illicites, le cannabis est la substance la plus utilisée (2,5 % au cours de la dernière année), suivi de la cocaïne (0,9 %) et du crack (0,3 %). De manière générale, les hommes présentent des prévalences de consommation plus élevées, à l’exception des médicaments utilisés sans prescription. Malgré les progrès réalisés dans les politiques de lutte contre le tabagisme, des défis persistent en ce qui concerne l’alcool, la cocaïne et le crack, ainsi que l’émergence de nouvelles substances et l’accès limité aux traitements. La mise à jour périodique des enquêtes nationales et l’élargissement des stratégies de réduction des risques et des dommages sont essentiels pour améliorer les réponses en santé publique.

Bipolar disorder (BD) is a severe mental illness associated with cognitive and functional impairment. This cross-sectional study evaluated the heterogeneity of cognitive and psychosocial functioning in BD, compared cognitive performance between BD and dementia groups, and identified factors associated with cognitive dysfunction. The study included 108 individuals with BD, of whom 32 were euthymic, while the remainder were symptomatic and 39 with major neurocognitive disorder. Sociodemographic data and mood symptoms were collected through structured interviews. Cognitive and functional status were assessed using the Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), neuropsychological tests, and the Functioning Assessment Short Test (FAST). BD participants were classified into three cognitive-functional profiles: Dementia-like (BD-DL; N = 69), Mild (BD-M; N = 22), and Preserved (BD-P; N = 17), based on MoCA and FAST scores. A multivariate analysis of covariance, adjusted for age and years of education (Pillai's Trace = 0.65, F = 6.14, p < 0.001; Wilks' Lambda = 0.39, F = 7.96, p < 0.001) showed significant group differences in neuropsychological tests. BD-P showed the highest performance in semantic and phonemic fluency, immediate verbal memory (RAVLT A1), and delayed verbal memory (RAVLT A7) while a pronounced impairment was observed in BD-DL and Dementia. Multinomial logistic regression analyses indicated that younger age, lower rates of hypertension, and fewer depressive symptoms were associated with greater odds of belonging to the BD-P and BD-M groups compared with the Dementia. Our findings support distinct cognitive-functional subgroups and indicate that cognitive deficits in BD may approximate the severity observed in dementia.

The scarcity of primary data and challenges in analyzing secondary data hinder comprehensive mental health monitoring and the development of evidence-based policies. In Brazil, although multiple health information systems capture critical mental health data, these systems lack integration, robust analysis, and systematic presentation of mental health indicators. This study introduces the Digital Public Mental Health Dataset, a comprehensive, transparent, and reproducible data resource that consolidates data from existing Brazilian health information systems. This dataset enables detailed tracking of mental health indicators, supports future research, and informs public health interventions to address mental health disparities.

OBJECTIVES:Three clinical staging models for bipolar disorder (BD) have been published, each with a different but complementary approach and focus. The International Society for Bipolar Disorders Staging Task Force aimed to integrate these models into one comprehensive three-dimensional staging model, separately rating bipolar spectrum, nonmood psychopathology, and (inter-episodic) functional impairment. METHOD:Via a series of in-person and online meetings, Delphi-surveys, and email discussions, the task force members step-by-step reached consensus on the overall structure of the model and the definition of the various stages. RESULTS:The resulting BD staging model describes the progression of mood psychopathology, nonmood psychopathology, and functional impairment in three independently rated dimensions. The stages of the mood psychopathology are M0 (at risk for BD having a 1st or 2nd degree family member with BD); M1 (prodromal); M2 (first episode classifying for BD-I or BD-II); M3 (recurrent BD); and M4 (chronic unremitting BD), with various substages. Single or recurrent major depression in persons at familial risk for BD is positioned in stage M1. The stages for nonmood psychopathology are: N0 (no symptoms); N1 (subsyndromal symptoms); N2 (one nonmood disorder); N3 (two nonmood disorders); N4 (three or more nonmood disorders). The stages for functional impairment are: F0 (no); F1 (mild); F2 (moderate); F3 (marked); and F4 (severe impairment). Fictitious case vignettes are presented to demonstrate how to apply the model. Limitations of clinical staging are discussed. CONCLUSION:The proposed three-dimensional clinical staging model for illness progression comprehensively captures the complexity of illness presentation and heterogeneous illness progression in BD, including psychiatric comorbidities and degree of functional impairment. The model provides a framework that requires validation in research and clinical practice.

OBJECTIVE:Autism spectrum disorder (ASD) is clinically heterogeneous, and adult presentations, especially among individuals requiring Level 1 support, may be subtle, shaped by adaptation, and obscured by comorbidity and diagnostic overshadowing. We review the historical evolution of autism-related constructs and their implications for recognising and interpreting ASD in adults. METHODS:We conducted a narrative review in MEDLINE (PubMed). Searches combined "autism", "autism spectrum disorder", and "ASD" with predefined constructs (central coherence, theory of mind, social skills, sensory processing differences, repetitive behaviours, restricted and intense interests, executive functions, alexithymia, sleep disturbances, motor abnormalities, and camouflaging). A second search focused on adult autism (adulthood, autistic adults, late diagnosis, and compensatory mechanisms). Grey literature was also considered; publications available up to December 2025 were included. RESULTS:The literature reflects a progressive refinement of the autism construct from descriptive behavioural syndromes to mechanism-oriented models that better accommodate phenotypic variability across development. In adults, these constructs help explain how pragmatic-communication difficulties, rigidity, intense interests, sensory reactivity, and executive-attentional differences can coexist with preserved language and intelligence. Recognition of compensatory strategies and social camouflaging helps explain delayed or missed diagnoses and associated distress. Shifts in diagnostic boundaries and awareness complicate inference from apparent prevalence increases. CONCLUSION:A historically grounded, construct-based framework can improve recognition of clinically meaningful adult ASD, sharpen differential diagnosis amid comorbidity, and support nuanced interpretation of changing diagnostic practices and epidemiological findings. It may inform individualized assessment and support planning as occupational, relational, and adaptive demands increase across adulthood substantially.

Aim The current study aims to identify master regulator genes (MRGs) in blood samples from individuals with bipolar disorder (BD) during both acute episodes and remission periods. Methods In this study, we combined transcriptomic data with computational techniques to characterize disease-related molecular signatures through an in-depth analysis of differentially expressed genes (DEGs), proteins, and pathways. Five transcriptomic datasets, comprising a total of 165 blood samples from BD case-control studies, were analyzed to identify DEGs and construct transcriptional networks. Master regulator analysis (MRA) and gene set enrichment analysis (GSEA) were employed to identify key master regulator genes (MRGs) and associated biological processes across the different mood states of BD. Results The study identified 59 MRGs, with DMTF1 emerging as a common gene across all phases of BD, suggesting its potential as a universal biomarker. Additionally, phase-specific genes were identified: CLOCK and SETDB2 in depression, ZNF358 and ZNF787 in euthymia, and ELF4 in mania. These genes were linked to significant biological processes such as glucocorticoid receptor signaling in depression, inflammation in mania, and telomere protein regulation in euthymia. Conclusions Our findings provide valuable insights into the molecular mechanisms underlying BD and underscore the potential of MRGs as diagnostic biomarkers and therapeutic targets, particularly the role of DMTF1 in BD pathogenesis across different mood states. Despite these promising results, further research is needed, including studies with larger sample cohorts and biological validation through molecular biology methods.

BACKGROUND:Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by difficulties in communication, deficits in social interaction, and repetitive behavioral patterns. Global prevalence estimates range from 1% to 2%, with variations attributed to cultural, social, and methodological factors. In Africa, research remains limited and highly heterogeneous, largely due to scarce diagnostic resources, persistent stigma, and the absence of consistent public policies. METHODS:A systematic search was conducted across PubMed, Embase, Scopus, and PsycInfo for articles published up to May 2025. Cross-sectional studies conducted in school-based or community populations were included. The analysis followed PRISMA guidelines, and the protocol was registered with PROSPERO (CRD420251138668). A random-effects model using the Freeman-Tukey transformation for variance stabilization was employed for statistical synthesis. RESULTS:Seven studies from Egypt, Kenya, Uganda, and Nigeria, comprising 71,341 participants, were included. Across included studies, reported ASD prevalence ranged from 0.54% to 23.8%. When pooled and stratified by methodological criteria, clinically confirmed ASD prevalence was 1% (95% CI, 0.0-1.0%), whereas high-risk screening prevalence was 4% (95% CI, 0.0-16.0%), with very high between-study heterogeneity (I² = 99.8%). CONCLUSION:Despite substantial methodological heterogeneity, ASD prevalence estimates in Africa appear comparable to those reported in high-income countries. The marked disparity between high-risk screening prevalence and confirmed diagnoses highlights the urgent need to expand diagnostic confirmation services and strengthen training for primary healthcare professionals to bridge the gap between risk identification and definitive diagnosis across the continent.

OBJECTIVES:We compared the prevalence of mental health disorders (MHD) among university students and non-student peers profiting from data obtained at the largest Brazilian health survey. STUDY DESIGN:Cross-sectional analysis from the 2019 Brazilian National Health Survey, a nationwide representative household probability survey. METHODS:We included participants between 18 and 24 years, classifying them as university students, if attending undergraduate or postgraduate education, or as non-students otherwise. Outcomes included self-reported lifetime diagnoses of depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder, and other psychiatric conditions, as well as screening for depression using the PHQ-9. Prevalence ratios were calculated using Poisson regression models controlling for sociodemographic variables and access to health services. Sex and income were evaluated as effected modifiers through stratified analysis. RESULTS:Among 12,633 young adults (2269 students; 10,364 non-students), students were more frequently women, White, from higher-income households, and greater health service access. After controlling for sociodemographic variables, compared to non-students, university students presented Adjusted PR(APR) of 1.58 [IC 95% 0.99-2.54] for self-reported depression, APR 1.21 [IC 95% 0.85-1.71] for a positive screening for depression, and APR 1.26 [IC 95% 0.89-1.8] for any other psychiatric diagnosis. Among males, students presented higher PR for all outcomes, but associations were non-significant among females. CONCLUSIONS:MHD prevalence among Brazilian university students was comparable to non-students indicating that MH may be a broader public health challenge among youth, irrespectively of university attendance. Inside universities, better understanding of vulnerable populations is necessary to plan prevention strategies, particularly for men.

INTRODUCTION:Substance Use Disorders (SUD) are among the most common comorbidities in individuals with Bipolar Disorder (BD). However, the prevalence of cocaine use disorder (CUD) and its impact on the clinical course of BD have not been extensively explored and synthesized to date. OBJECTIVE:To estimate the prevalence of CUD among individuals with BD and describe its associated clinical correlates. METHODS:We conducted a systematic review with meta-analysis and meta-regression following PRISMA guidelines. Six databases were searched through December 2024. We included observational studies reporting CUD prevalence or clinical comparisons between BD individuals with and without CUD. Risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used for meta-analyses. RESULTS:Twenty-seven studies comprising 6150,881 individuals with BD were included in the meta-analysis. The pooled overall prevalence of CUD in BD was 10.94% (95% CI: 6.15-18.73), rising to 46.25% (95% CI: 34.77-58.15) in studies including primary SUD samples; heterogeneity across studies was high. Seven studies were included in the qualitative synthesis of clinical correlates. BD+CUD individuals showed worse affective symptoms, higher rates of psychiatric comorbidities (e.g., post-traumatic stress disorder, attention-deficit/hyperactivity disorder), polysubstance use, and lower medication adherence compared to BD individuals without comorbid CUD. Sociodemographic vulnerability and increased risk behaviors were also more frequent. Although cognitive performance was broadly similar, BD+CUD patients performed slightly better than BD+AUD in delayed recall, possibly reflecting substance-specific effects. CONCLUSION:CUD is common among individuals with BD and is associated with more severe clinical profiles. Findings highlight the need for integrated treatment strategies and greater clinical attention to this comorbidity.

Background: Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a trophic factor, decreases ER stress by modulating the UPR. The objective of this study is to investigate the MANF-ER stress pathway in BD and major depressive disorder (MDD) compared to healthy controls (HC). Methods: MANF protein concentration and MANF and GRP78 gene expression were assessed in peripheral blood from individuals with BD, MDD, and HC (protein: 40 BD, 55 MDD, 55 HC; gene expression: 52 BD, 61 MDD, 69 HC). MANF protein and gene expression along with GRP78 gene expression were also analyzed in postmortem brain tissue (20 BD, 20 MDD, 19 HC). MANF protein was quantified using an ELISA assay while quantitative polymerase chain reaction was used for MANF and GRP78 gene expression. Results: Peripheral MANF protein levels were reduced in individuals with BD in a depressive state compared to controls (P = .031) and euthymic BD participants (P = .013). No significant differences in MANF or GRP78 gene expression were observed in BD irrespective of mood state, or MDD compared to HC (all P > .05). No differences were observed regarding MANF/GRP78 protein or gene expression levels in postmortem tissue (P > .05). Conclusions: Individuals with BD who were in an acute depressive phase were found to have reduced peripheral MANF levels potentially signifying abnormal UPR and supporting the notion that BD is associated with increased ER stress.

OBJECTIVE:Autism spectrum disorder (ASD) and bipolar disorder (BD) pose significant diagnostic challenges due to their clinical complexity. This review aims to examine the interface and overlapping features of these conditions, with a particular focus on the challenges associated with their comorbidity. METHODS:We conducted a narrative review to examine clinical overlap, common psychiatric comorbidities, and a shared neurobiological basis between ASD and BD. RESULTS:There is a notable convergence of symptoms in ASD and BD, including mood instability and emotional dysregulation; irritability, impulsivity, and aggressive behavior; deficits in social skills and social cognition; impairments in executive functions; sleep disturbances; problematic sexual behaviors; and sensory sensitivities. Common psychiatric comorbidities and shared neurobiological basis further underscore this potential interplay. CONCLUSION:Despite distinct clinical trajectories and diagnostic criteria, our findings indicate a significant overlap in symptoms and clinical presentations between ASD and BD. This complexity makes it challenging to identify the co-occurrence of ASD and BD, which can lead to difficulties in accurately diagnosing and managing both conditions simultaneously.

Introduction A substantial proportion of individuals with bipolar disorder (BD) show some degree of cognitive impairment. Emerging evidence suggests that lifestyle-based interventions (LBIs) can improve clinical outcomes in BD, although few studies have assessed their efficacy on cognition. Aim To evaluate the methodological quality and efficacy of randomized controlled trials (RCTs) comprising LBIs for improving cognition in people with BD. Methods A systematic search following PRISMA guidelines. PubMed, Embase, Scopus, Web of Science, PsycINFO and ClinicalTrials.gov were searched from inception until February 1st, 2024. RCTs examining the effects of LBIs on cognition, assessed by validated neuropsychological tests, in individuals with BD (of any age, mood or comorbidity) were eligible. Risk of bias and methodological quality were assessed with the Cochrane RoB 2 tool and the PEDro scale, respectively. Results were narratively synthesized. Results Seven RCTs ( = 275) were included, each targeting one lifestyle domain. Six assessed nutraceuticals (e.g., vitamins B1/B6, DHA, NAC, citicoline, creatine) and one evaluated a mind-body intervention (Tai Chi/Qigong). Two RCTs reported pro-cognitive effects of nutraceuticals: citicoline was associated with improvements in declarative memory and verbal learning, and creatine with improved verbal fluency. Mean intervention duration was 12 weeks. Cognition was a primary outcome in three RCTs. Overall, methodological quality was high, and risk of bias was low. Conclusion Specific nutraceuticals may offer pro-cognitive effects for BD. However, the evidence is limited by the small number of included studies and substantial heterogeneity in populations, interventions, and cognitive assessments. Future studies should examine whole-diet, physical activity/exercise and multimodal LBIs.

OBJECTIVES:Bipolar disorder (BD) and major depressive disorder (MDD) are mood disorders. The most frequent clinical presentation of BD and MDD is depression, which contributes to high rates of misdiagnosis between disorders. To support diagnostic discrimination and therapeutic stratification, we aim to perform a systematic review and meta-analysis evaluating peripheral protein inflammatory biomarkers between BD and MDD, with a focus on the depressive state. METHODS:We conducted a literature search on PubMed, PsycInfo and Embase with no year/language restrictions. Original studies including human participants with a BD or MDD diagnosis which directly compared levels of peripheral protein inflammatory biomarkers between groups were included. A random effects meta-analysis was performed. RESULTS:35 studies were included in the systematic review. 9 studies were included in the meta-analysis. The meta-analysis showed IL-7 (p < 0.01) levels were significantly decreased in BD, and IL-9 (p < 0.01), CCL3 (p = 0.03), CCL4 (p = 0.01), CCL5 (p = 0.02) and CCL11 (p = 0.04) levels were significantly increased in BD. LIMITATIONS:High heterogeneity and limited dataset size restricted our meta-analysis to a small subset of biomarkers and limited our exploration of the effects of moderator variables. CONCLUSION:This study found differences in IL-7, IL-9, CCL3, CCL4, CCL5 and CCL11 between BD and MDD in a depressive state. These findings support the notion that inflammation is associated with mood disorder pathophysiology, particularly with respect to T-cell network dysregulation. Further studies can assist in better understanding differences between disorders and work towards clinical applications.

Recurrent course and disruption of circadian rhythms are among the core features of bipolar disorder (BD). Thus, ongoing symptom monitoring is an essential part of good clinical management. We conducted a study to validate the English version of the ASERT (Aktibipo questionnaire), a tool for self-assessment of mood symptoms. We also analyzed the relationship of self-assessed symptoms with clinician ratings and actigraphy measures, and investigated the possibility of predicting depressive episodes using subjective and digital measures. This was a longitudinal study of twenty individuals with BD, followed for up to 11 months. The participants completed weekly mood self-assessments (ASERT) using a smartphone app and wore wrist actigraphs. During monthly appointments, the severity of their mood symptoms was rated by clinicians, and the participants completed questionnaires addressing overall functioning (FAST), and biological rhythms (BRIAN). The study confirmed the validity and reliability of the ASERT as a measure of subjective mood. Additionally, we found significant associations between ASERT responses, clinical scales, and actigraphy data (ASERT_dep vs. MADRS β = 1.42, p < 0.001, ASERT_man vs. YMRS β = 0.38, p < 0.001, mixed-effect model). In our analysis, a combination of self-assessment and actigraphy data detected depression relapse with 67