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Objective: In this population-based cohort study, we compared the risks of incident hyperopia, myopia, astigmatism, and strabismus between children with autism spectrum disorder (ASD) and those without ASD. Methods: This study included children who were born in Taiwan at any time between 2004 and 2017, using data from the Taiwan Maternal and Child Health Database (TMCHD). We included 20,688 children with ASD and 2,062,120 matched controls to estimate the risks of incident hyperopia, myopia, astigmatism, and strabismus. Cox proportional hazards regression models were conducted for risk assessment. Models were adjusted for sex, calendar year of birth, and gestational age at birth. Statistical significance was determined through adjusted hazard ratios (aHRs) and 95%CIs. Results: Children with ASD had higher risks of incident hyperopia (aHR: 1.78; 95%CI 1.70-1.86), myopia (aHR: 1.27; 95%CI 1.24-1.30), astigmatism (aHR: 1.51; 95%CI 1.46-1.56), and strabismus (aHR: 2.18; 95%CI 2.05-2.32) compared to children without ASD. Conclusion: Clinicians should screen children with ASD for potential eye conditions. Further studies are required to elucidate the mechanisms linking ASD with eye diseases. In addition, studies should explore how the type and severity of ASD symptoms influence the detection of these eye conditions.

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Objective: This study investigated whether moral harassment contributes to anxiety, depression, and burnout among medical residents. Methods: This three-stage longitudinal study involved 218 1st-year residents, of whom 76 (34.9%) participated in all stages. The questionnaire covered demographics, mental health (using the Patient Health Questionnaire-4), burnout (using the Maslach Burnout Inventory Human Services Survey), and harassment experiences. Mental health outcomes and harassment were analyzed using logistic regression. Results: Anxiety and depression scores varied significantly, including a notable decrease in the personal accomplishment dimension of burnout. The prevalence of harassment was above 90%, and most victims were disturbed by the harassment they suffered. While a direct correlation between harassment victimization and reduced mental health was not found, seeking help exacerbated suffering, and depression and emotional exhaustion increased less among surgical residents. Conclusion: To the extent of our knowledge, this is the first longitudinal study on mental health and harassment among medical residents. The mental suffering experienced after taking action against harassment suggests that safe environments for addressing these issues are lacking in medical residencies. Further studies concerning surgical residents could shed light on their lower levels of suffering. Institutional changes are needed to support victims and create a healthy environment.

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Objective: This study aimed to explore the association between major depressive disorder (MDD) and suicide risk in patients with dementia. Methods: A cohort of 625,218 individuals aged ≥ 40 years with dementia was identified from Taiwan’s National Health Insurance Research Database (NHIRD) between 2007 and 2018. After excluding prevalent cases in 2007, a nested case-control study enrolling 1,256 suicide cases and 5,022 matched controls was conducted. The frequencies of MDD-related outpatient or inpatient visits over a 7-year period preceding the event dates were calculated and analyzed for association using conditional logistic regression. Results: Dementia comorbid with MDD was associated with increased suicide risk (adjusted OR [AOR]: 2.67), particularly in individuals with ≤ 1.0 MDD episodes per year (AOR: 2.85). A similar association was observed only in individuals aged ≥ 65 years and males, with a pronounced risk of suicide in those experiencing ≤ 1.0 MDD episodes per year (AOR: 3.08 for individuals aged ≥ 65 years; AOR: 3.28 for males). Conversely, the risk increase was evident with > 1.0 MDD episodes per year in those aged < 65 years (AOR: 3.04) and females (AOR: 2.45). Conclusion: MDD is associated with suicide risk in patients with dementia. The strength of this association possibly varies with age and gender.

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Objective: Patient response to antipsychotic drugs varies and may be related to clinical and genetic heterogeneity. This study aimed to determine the performance of clinical, genetic, and hybrid models to predict the response of patients in first-episode psychosis (FEP) to the antipsychotic risperidone. Methods: We evaluated 141 antipsychotic-naive FEP patients before and after 10 weeks of risperidone treatment. Patients who had a response rate equal to or higher than 50% on the Positive and Negative Syndrome Scale (PANSS) were considered responders (n=72; 51%). Analyses were performed using a support vector machine (SVM), k-nearest neighbors (kNN), and random forests (RF). Clinical and genetic (with single-nucleotide variants [SNVs]) models were created separately. Hybrid models (clinical + genetic factors) with and without feature selection were created. Results: Clinical models presented greater balanced accuracy (63.3%; CI 0.46-0.69) with the SVM algorithm than the genetic models (balanced accuracy: 58.5% [CI 0.41-0.76], kNN algorithm). The hybrid model, which included duration of untreated psychosis, Clinical Global Impression-Severity (CGI-S) scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84], RF algorithm). Conclusion: A hybrid model including clinical and genetic predictors can enhance prediction of response to antipsychotic treatment.

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Objective: To study the impacts of maternal depressive symptoms trajectories and harsh parenting and explore if the maternal quality of life (QoL) mediates this association. Methods: We used data from the 2004 Pelotas Birth Cohort, a population-based longitudinal study from Pelotas, Brazil (n=3,285 mothers, complete cases analysis). We used the Edinburgh Postnatal Depression Scale (EPDS) to assess maternal depressive symptoms and calculated their trajectories from 3 months until the 11-year follow-up using a group-based modeling approach. Psychological and physical aggression were measured using the Parent-Child Conflict Tactics Scale (CTSPC). Maternal QoL was measured by the question “How is your quality of life?” Data were analyzed using path models in Mplus. Results: All maternal depressive symptoms trajectories increased the frequency of psychological and physical aggression at early adolescence when compared to the reference group. Mediation analysis indicated that maternal depressive symptoms led to low levels of perceived maternal QoL, which in turn was associated with increased use of harsh parenting. The proportion of total effect explained by maternal QoL ranged from 4.04% (0.00-5.58%) to 16.31% (10.88-19.10%). Conclusion: Our findings, within a longitudinal framework from a middle-income country, support existing evidence that maternal depressive symptoms are associated with harsh parenting. Our results also suggest that one mechanism underlying this association is lower perceived maternal QoL.

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Objective: We investigated whether a wide range of baseline mental disorders among university students predict Internet gaming disorder (IGD) 1 to 3 years later. Methods: This prospective cohort study was conducted in six Mexican universities and had a 1- to 3-year follow-up period (September 2018 to June 2022). Participants were 1st-year university students (n=2,144) free of symptoms indicative of IGD at entry (baseline). Ten mental disorders (bipolar, major depressive disorder, generalized anxiety disorder, panic disorder, alcohol use disorder, drug use disorder, binging and/or purging, intermittent explosive disorder, psychotic experiences, and attention deficit hyperactivity disorder) at baseline were investigated as risk factors for IGD at the end of the follow-up. We used Cox regression to model the IGD incidence rate. Results: Any baseline mental disorder was associated with a 2.33 times (1.26-4.31) higher rate of IGD 1 to 3 years later. Several individual disorders were associated with rates of IGD in multiple models, with comorbid conditions diminishing most of these associations. Conclusion: Only major depressive disorder and bipolar disorder remained associated with new cases of IGD. The discrepant results of longitudinal studies on the role of specific mental disorders in the development of IGD should be further investigated.

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Objective: Functionality and quality of life levels were measured in caregivers of patients with bipolar disorder, investigating the associations between them and with clinical and sociodemographic data. Method: A cross-sectional study was conducted between 2020 and 2022 with caregivers of patients with bipolar disorder treated in a university hospital’s outpatient clinic. The following instruments were applied: a clinical and sociodemographic questionnaire, the World Health Organization Disability Assessment Schedule 2.0, the 36-Item Short Form Health Survey, the Mini International Neuropsychiatric Interview Plus, and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders. Results: The median World Health Organization Disability Assessment Schedule 2.0 score was < 20, and the median score on the 36-Item Short Form Health Survey domains was > 60. Caregivers with greater functional impairment had lower quality of life. Being younger, being a parent, having non-psychiatric clinical conditions, and having mental disorders were associated with lower quality of life and functionality. Conclusion: These results indicate less functional impairment and better perceived quality of life than what has been reported in the literature, demonstrating that there is a subgroup of caregivers who perform their role without significant compromise to these health aspects. Exploring other factors associated with functionality and quality of life, such as resilience, psychological support, etc., may allow for more targeted public health interventions, optimizing comprehensive bidirectional care for patients and caregivers.

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Objective: Given the increasing number of people with dementia in Brazil, health and social systems must urgently plan strategies to meet the needs of this population and their families. Therefore, research on dementia costs is essential. This study estimated direct and indirect dementia-related costs in Brazil. Methods: We used a cost-of-illness methodology to estimate dementia-related costs, in addition to household interview data from the National Report on Dementia in Brazil (ReNaDe) and public national databases to collect data on health service use and costs. Both a social and a health system perspective were used. Results: The monthly cost of dementia per patient increases with advancing stages of the syndrome: USD 843.04 in the initial stage, USD 1,317.81 in the intermediate stage, and USD 1,576.15 in the advanced stage. Indirect costs represent ≥ 73% of total expenses. The country’s total expenses are the highest during the intermediate stage of dementia. Conclusion: Family caregivers shoulder at least 73% of the health-related costs of dementia in Brazil, highlighting the need for better support strategies for people with dementia and their families.

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Objective: Sleep problems are common in patients with psychotic disorders, especially schizophrenia. Although pharmacological methods are at the forefront of treatment, they have some drawbacks. Cognitive behavioral therapy for insomnia (CBT-I) is an option for the treatment of individuals with insomnia; in recent years, interest in its use in patients with psychotic disorders has been increasing. This meta-analysis aims to evaluate the effectiveness of CBT-I for sleep problems in patients with psychotic disorders. Methods: A systematic search of the PubMed, Scopus, and EBSCO (MEDLINE) databases was conducted to identify relevant studies. The inclusion criteria were randomized controlled trials (RCTs) and uncontrolled studies that focused on participants diagnosed with schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorders, or unipolar depression with psychotic features, who had had sleep problems for at least 1 month, and who were receiving treatment. The initial search yielded 246 studies, of which eight were ultimately selected for meta-analysis after screening and applying inclusion and exclusion criteria. Statistical analysis was conducted in the R software environment. Results: CBT-I significantly ameliorates insomnia and sleep quality in patients with psychotic disorders in both the short and long term. Additionally, CBT-I leads to significant improvement in psychotic symptoms in the short-term period and contributes significantly to improvement in mental well-being in both short- and long-term follow-up. Conclusions: CBT-I is an effective, valuable method for sleep problems in patients with psychotic disorders. Its widespread use for this purpose is recommended.

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Objective: Suicide represents 1% of all deaths in the world, and it is more prevalent in developing countries. Because suicide mortality has been growing in recent years in Brazil, we investigated whether patients who committed suicide in 2022 in Fortaleza sought care in the state’s only psychiatric emergency service before the act. Methods: This retrospective cross-sectional study used data from electronic psychiatric emergency records and reports from the state department of forensics. Results: A total of 292 deaths (25% women) were identified, representing almost 2% of mortality in Fortaleza that year. Only 2.7% of those who committed suicide during this period requested an emergency psychiatric evaluation in the 3 months prior to death. Of these individuals, 75% mentioned suicidal ideation. Most deaths (70%) were due to hanging. Conclusion: The majority of patients who committed suicide in Fortaleza in 2022 did not seek care from the psychiatric emergency service prior to the event; further studies are needed to investigate the causes of this behavior.

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Objective: To assess longitudinal patterns of anxiety, depression, and posttraumatic stress symptoms, as well as their predictors, among workers at a referral hospital during the first two waves of the coronavirus disease 2019 (COVID-19) pandemic in Brazil. Methods: Data were collected between July 2020 and June 2021 (n=1,078). Anxiety, depression, and posttraumatic stress symptoms were assessed using three self-report scales: the Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Impact of Event Scale-Revised (IES-R). Predictor analysis included COVID-19-related events, fear of COVID-19, and institutional support. Statistical analysis involved linear mixed models (LMM) and local polynomial regressions. Results: Anxiety and depression trended towards increased reactivity, while posttraumatic stress presented a downward trend over follow-up, with less fluctuation. Predictor analysis showed that higher levels of institutional support were associated with a reduced risk of all adverse mental health outcomes; conversely, greater fear of COVID-19 was positively associated with all such outcomes. Conclusion: Our findings underscore the importance of allocating enhanced attention and resources to effectively addressing personal health challenges among the health workforce, emphasizing the significance of organizational support and continuous monitoring of emotional distress.

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Objective: To evaluate the effect of narrative therapy on post-traumatic stress disorder (PTSD) symptoms, perceived stress, anxiety, and depression in nurses. Methods: A total of 92 clinical nurses with positive PTSD symptom screening results were randomly assigned (1:1) to the intervention or control group. The intervention group received narrative therapy and a psychological stress leaflet, while the control group received only a psychological stress leaflet. PTSD, perceived stress, anxiety, and depression were measured before and after the intervention to assess the effect of narrative therapy. Results: After the intervention, the intervention group showed significantly lower PTSD symptom levels (p = 0.025), perceived stress (p = 0.033), anxiety (p = 0.004), and depression (p = 0.015) than the control group. Regarding the dichotomous PTSD, anxiety, and depression outcomes, there was a statistically significant decrease in the number of positive cases of PTSD (p = 0.030) and anxiety (p = 0.002), but no significant change in the number of positive cases of depression (p = 0.060). Conclusion: Narrative therapy is expected to alleviate PTSD symptoms, stress, anxiety, and depression among frontline clinical nurses, and healthcare managers should consider narrative therapy interventions to improve the mental health of their nursing staff. Clinical trial registration: ChiCTR2200058472. Registration date: April 09, 2022. Date of first recruitment: June 1, 2022.

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Objective: We assessed the effect of N-acetylcysteine, as an adjuvant treatment, on treatment adherence (primary outcome) according to peripheral biomarkers and clinical improvement (secondary outcomes) in patients with alcohol use disorder. Methods: A 9-week randomized, double-blind, placebo-controlled clinical trial was conducted on 53 (n = 25 N-acetylcysteine, n = 28 placebo) inpatients with alcohol use disorder. Neuropeptide Y, oxidative stress and inflammatory biomarkers, and hepatic parameters were analyzed at 3 time points. Results: Seventeen (60.7%) patients in the placebo group and 16 (64%) patients in the N-acetylcysteine group completed the trial. Hepatic biomarker levels changed significantly over time (p < 0.001). Oxidized glutathione levels at admission were lower in the N-acetylcysteine group (ppairwise = 0.043). By the end of the study, both groups had similar oxidized glutathione levels (p = 0.868), and oxidized glutathione levels were lower in the placebo group. At the end of the intervention, superoxide dismutase activity had decreased and neuropeptide Y levels had increased in the N-acetylcysteine group. Both groups showed similar mean time to relapse, treatment adherence, and clinical improvement. Conclusions: Our findings reinforce the effects of alcohol on oxidative stress and neuropeptide Y parameters. However, our sample size may limit the generalizability of the results, especially for clinical outcomes. Future randomized clinical trials including patients with less severe alcohol use disorder and longer follow-up may be needed to determine whether N-acetylcysteine could help reduce the mental health burden of this disorder. Clinical Trial Registration: NCT03018236.

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Objective: Internalizing problems disproportionately affect females in adolescence and adulthood, but research at earlier ages is limited due to a focus on disruptive behaviors. Our study addresses this gap by exploring the structure of internalizing problems and gender differences in Brazilian preschoolers. Methods: We analyzed data from the Child Behavioral Checklist 1.5-5 (CBCL 1.5-5) as administered in the Preschool Mental Health Study (PreK Survey), involving 1,292 children aged 4 to 5 in Embu das Artes, state of São Paulo, Brazil. Confirmatory factor analysis and comparisons of means explored internalizing problems and gender variations. Results: A two-factor model best fit both internalizing and externalizing problems. A hierarchical model with four factors (emotionally reactive, anxiety/depression, somatic complaints, and withdrawn) best fit internalizing problems, achieving partial invariance between boys and girls. Boys scored higher in the withdrawn syndrome, while girls scored higher in the somatic complaint syndrome. Conclusion: Preschoolers’ internalizing problems warrant attention beyond their link to externalizing problems. While the overall construct is similar in boys and girls, divergent syndrome scores indicate potential distinct risk patterns requiring further exploration.

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Objective: The large body of literature examining the association between parenthood and mortality in the general population contrasts with a lack of such studies on older adults with schizophrenia. Identifying potential protective factors of premature death in this population is important to help guide prevention measures. Here, we examined whether all-cause and cause-specific mortality rates significantly differ between older parents and non-parents with schizophrenia during a 5-year follow-up. Methods: We used data from a 5-year prospective multicenter sample of older adults with an ICD-10 diagnosis of schizophrenia (aged 55 years or more) recruited in France. We performed a forward stepwise logistic regression to examine the association between parenthood and all-cause mortality, including only independent variables that best explain outcome. Results: Of the 323 older adults with schizophrenia, 133 (41.2%) were parents (mean age = 67.0, SD = 6.1) and 190 were not (mean age = 67.2, SD = 6.6). Following adjustments, parenthood was significantly associated with lower all-cause mortality compared to patients without children (21.1% [n=28] vs. 35.8% [n=68]; AOR = 0.50; 95%CI 0.27-0.94; p = 0.032); the association involved no significant sex differences. Conclusion: Parenthood could be a protective factor against mortality among older patients with schizophrenia who live in France. Further research is needed to understand the specific mechanisms underlying this association.

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Objective: Disordered eating behaviors (DEB) are dysfunctional changes in eating behavior that do not meet the diagnostic criteria for eating disorders. DEB affect a significant percentage of individuals, yet the topic remains under-researched. The current study investigates the developmental trajectory and psychopathological correlates of DEB in children and adolescents in Brazil. Methods: The sample included 1,583 participants from the Brazilian High-Risk Cohort who were assessed across three waves between 2010 (age 6-12 years) and 2019 (age 12-21 years). Psychopathology was assessed through the Development and Well-Being Assessment, and DEB was assessed through Development and Well-Being Assessment’s eating disorder section. Dimensional psychopathology was measured with the Child Behavior Checklist. Results: The participants were divided into dysfunctional and non-dysfunctional eating groups. DEB varied significantly, with few participants having a persistent pattern. DEB were strongly linked to higher internalizing symptoms, especially in girls, but less to externalizing behaviors. DEB increased the likelihood of eating disorders, major depressive disorder, and higher body mass index. Conclusion: This study reveals that DEB are frequent among Brazilian children and adolescents and are linked to psychopathology (especially internalizing symptoms) and body mass index. Future research should investigate the underlying mechanisms of DEB and develop strategies for early detection and effective interventions.

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Objective: This study aimed to explore the relationship between suicidal behavior and various factors, including peripheral inflammatory markers, atherogenic indices, serum albumin levels, impulsivity, and aggression. Methods: This cross-sectional study included 100 patients hospitalized for a recent suicide attempt, 74 individuals with psychiatric disorders without a recent suicide attempt, and 85 healthy controls (HC). Peripheral inflammatory markers, atherogenic indices, and serum albumin levels were assessed using fasting blood samples. Impulsivity and aggression were measured with the Barratt Impulsiveness Scale-11 (BIS-11) and the Buss-Perry Aggression Questionnaire (BPAQ). Results: Serum albumin levels were significantly lower (p = 0.001), and the neutrophil-to-albumin ratio (NAR) was significantly higher (p < 0.001) in individuals who had recently attempted suicide, compared to both individuals with psychiatric disorders without a recent suicide attempt and the HC group. Logistic regression identified NAR (p = 0.001), low albumin levels (p = 0.017), impulsivity (p = 0.001), and aggression (p < 0.001) as significant predictors of suicidal behavior. Lower education (p = 0.001) and lifetime substance use disorders (p = 0.003) were also significant predictors. No significant differences were found in atherogenic indices. Conclusion: Low albumin levels and increased NAR are key predictors of suicide risk, underscoring the role of inflammation. Additionally, addressing educational disparities and substance use is crucial for suicide prevention strategies.

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Objective: To explore the association of 75 candidate genes previously reported in subjects with anxiety symptoms (AS) and depressive symptoms (DS) with such symptomatology in a Mexican cohort. Methods: The sample included 2,012 individuals from the Mexican Genomic Database for Addiction Research (MxGDAR/Encodat) cohort: 198 with AS, 266 with DS, 66 with both anxiety and depressive symptoms (ADS), and 1,482 healthy controls. The Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD) screening questionnaire was used to evaluate lifetime AS and DS. The sample was genotyped with the commercial microarray PsychArray BeadChip. We identified 707 single nucleotide polymorphisms (SNPs) of 75 genes previously associated with AS and DS. The PLINK logistic regression approach was performed to analyze the association between these SNPs and AS, DS, and ADS. Results: The analysis identified significant associations of LAMA SNP rs2437092 (p = 3.89 × 10-5) and MYO1H SNP rs11066591 (p = 4.06 × 10-5) with anxiety and depressive symptoms. Additionally, MBD5 SNPs rs7578002 and rs1234428 were associated with DS (p = 7.9 × 10-6 and p = 1.94 × 10-5, respectively). However, after adjustment for age, sex, and the three genetic principal components, only the associations of rs7578002 and rs1234428 with DS remained (p = 5.85 × 10-5 and p = 8.15 × 10-5, respectively). Conclusions: Our study replicated the association between MBD5 and DS. The MBD5 protein is involved in gene silencing, suggesting its potential implication in the development of DS in the Mexican population.

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Objective: The practice of using drugs to modulate experiences is a well-documented phenomenon worldwide, particularly among men who have sex with men (MSM). This study aims to describe patterns of drug combinations used by Brazilian MSM, embracing a detailed examination of the Brazilian context, which may inspire research elsewhere while enriching the global panorama on MSM drug use. By focusing on Brazilian MSM, the study sheds light on specific drug use combinations, which may help in the development of effective, culturally sensitive public health strategies. Methods: This investigation was conducted within the Latin American MSM Internet Survey, a pioneer online study addressing psychosocial and sexual health of MSM in the region. Conducted from January to May 2018, the survey garnered responses from over 18,139 Brazilian MSM. Using exploratory factor analysis through maximum likelihood estimation, the study identified distinct sub-groups of drug users among 15,499 participants after exclusion due to discrepant responses (Kaiser-Meyer-Olkin measure = 0.94 and Bartlett’s test ≤ 0.01), indicating adequate sampling and suitability for factor analysis across all substances. Results: The factor analysis revealed four primary drug combination groups among participants: Group One (Heavy Drug Users), Group Two (Party Drug Users), Group Three (Conservative Users), and Group Four (Classic Chemsex Users). Each group represents unique drug use patterns and preferences, from the use of potent stimulants to more socially accepted substances like tobacco and cannabis. Notably, Group One, identified as “heavy” drugs users, used particularly risky substances, including mephedrone, crack, crystal meth, heroin, and other synthetic stimulants. Conclusion: The findings reveal diverse and complex drug use patterns among MSM in Brazil. Understanding these patterns is essential for developing targeted interventions and support mechanisms for various sub-groups among MSM. Future research should focus on the health outcomes associated with these patterns and the social and psychological contexts of drug use.

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Objective: This study investigated the association between childhood family adversity and depression in a cohort of Brazilian adults over three visits. Methods: A total of 12,636 participants from the Longitudinal Study of Adult Health (ELSA-Brasil), baseline (2008-2010) and followed up in 2012-2014 and 2017-2019, were included. Five types of family dysfunction and the childhood family dysfunction score (0, 1, and ≥ 2 dysfunctions) were used. The Clinical Interview Schedule-Revised was used to assess depression in visits 1 and 2 or 3. Multinomial logistic regression models estimated crude and adjusted OR and 95%CI. Results: The mean age of the sample was 59.6 (SD, 8.8) years, 7.4% presented depression in one visit, and 2.2% presented it in two or three visits. After adjustment, compared to no family dysfunction, mental disorder (OR = 3.91; 95%%CI 2.94-5.21), substance abuse (OR = 2.14; 95%CI 1.65-2.77), and parental separation/divorce (OR = 1.55; 95%CI 1.12-2.15) increased the odds of depression in two or three visits. Exposure to ≥ 2 types of family dysfunction increased the odds of depression in one, and two or three visits in a dose-response gradient. Conclusion: Exposure to childhood family dysfunction contributes to the occurrence and recurrence of depression in adults. Interventions to prevent dysfunctional family environments and their repercussions on children can reduce the burden of depression.

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Objective: Depressive symptoms during the perinatal period significantly impact mothers and infants. Emerging evidence suggests a connection between gut microbiota and mood regulation. This study investigated whether depressive symptoms are associated with changes in the gut microbiota of women during the perinatal period. Methods: Thirty-four pregnant women were screened for depression using the Edinburgh Postnatal Depression Scale (EPDS) and categorized based on symptom severity. Stool samples were collected during the third trimester and at two postpartum timepoints. All samples underwent 16S rRNA gene sequencing and quantification of short-chain fatty acids (SCFA) by gas chromatography-mass spectrometry (GC-MS). Results: No differences in SCFA concentrations were observed between groups (p > 0.05). However, postpartum women with moderate to severe symptoms (MS group) had a significant increase in Enterobacteriaceae abundance compared to women with mild or absent symptoms (AM group) (p < 0.05). The Bifidobacterium genus increased significantly in both groups over time (p < 0.05). The MS group showed a reduction in depressive symptoms during psychiatric treatment (p < 0.05). Conclusion: These findings suggest a link between gut microbiota and perinatal depressive symptoms. Further research using microbiome-targeted approaches is needed to understand the broader implications for maternal health.

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Objective: This study’s purpose was to characterize copy number variations in a Brazilian cohort regarding frequency and inheritance patterns and to determine the effect of copy number variations previously associated with mental health disorders on the risk of developing these disorders. Methods: A total of 2,250 probands and 3,174 parents (897 trios) from the Brazilian High-Risk Cohort Study for Mental Conditions (BHRCS) were genotyped, with copy number variations detected using PennCNV software. Results: In total, 56.03% of the copy number variations were inherited. Among the distinct copy number variations, 96.15% were rare (frequency < 1% in the BHRCS). Duplications in 2q13 and 15q13.3 were less frequent, while those in 2q11.2 and 16p11.2 were more frequent in the BHRCS than in databases such as the Database of Genomic Variants and the Genome Aggregation Database. Of the 40 copy number variations previously associated with mental health disorders, 18 were identified in the sample. While duplication in 7q11.2 has been considered protective for schizophrenia, we found that deletion in 7q11.2 was protective for mental health disorders (p = 0.033, OR = 0.103). No significant results were found for the other copy number variations, despite mild effect sizes. Conclusions: This is one of the largest copy number variation studies to have been conducted in a Brazilian sample, and it will be a valuable resource for future meta-analysis, advancing our understanding of the genetics of mental health disorders, especially in diverse populations.

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Objective: This study aimed to mine and analyze adverse event signals of fluoxetine using the U.S. Food and Drug Administration’s Adverse Event Reporting System database. Methods: This study focused on suspected adverse drug reaction reports between the first quarter of 2004 and the second quarter of 2023 in which fluoxetine was the primary suspected drug. Four signal mining and analysis methods were employed to comprehensively assess adverse event signals. Results: A total of 19,932,732 reports were collected, of which 22,884 primarily suspected fluoxetine. Through analysis, 862 signs involving 27 system organ classes were identified. More adverse events were reported by female patients (58.81%) than male patients (26.84%), with the largest percentage being in the 18-45 year age group. The signal strength of adverse events related to pregnancy and neonatal conditions was notable, including fetal exposure during pregnancy, exposure during pregnancy, and neonatal health-related adverse events, such as atrial septal defect, premature baby, ventricular septal defect, and maternal drugs affecting the fetus. Conclusions: Although fluoxetine has been extensively approved and applied, its use in women who are pregnant or planning to conceive should be approached with caution.

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Objective: White matter hyperintensities (WMH) are associated with major depressive episodes (MDE) in individuals aged 65 and older. WMH are prevalent in adults under 65, yet the association between their volume and MDE in this population remains uncertain. This study aimed to assess the association of WMH volume with MDE and its severity in patients aged < 65. Methods: Cross-sectional study (ancillary to clinical trial NCT02051413) of subjects under the age of 65. Overall, 69 patients with MDE and 32 healthy controls (HCs) were included. Severity was assessed with the Hamilton Rating Scale (HRS) and WMH were quantified by two experts. Post-hoc mediation analyses were conducted if associations were found between independent variables and WMH. Results: Mean age was 34.5 (12.4) years. There was no difference in WMH between patients and HCs. Higher WMH volumes were observed in extremely severe MDE (2,170.2 [3,767.9] mm3 vs. 416.6 [594.9] mm3 [r = 0.21; p < 0.05]), which completely mediated the effect of age on severity. Conclusions: In a sample of adults under 65, this study failed to identify higher WMH volume in patients with MDE compared to HCs. However, WMH may act as a mediator of the association between age and MDE severity. This finding suggests that WMH could contribute to more severe depression in late life.

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Objective: This study assessed the safety profile of olanzapine by analyzing adverse events reported in the U.S. Food and Drug Administration’s Adverse Event Reporting System database, particularly focusing on newly identified risks. Methods: The study involved olanzapine-related adverse events that occurred between January 1, 2004, and June 30, 2023. Four signal mining methods were used for a comprehensive analysis of the frequency and strength of adverse events, including the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. Results: A total of 43,664 reports with olanzapine as the primary suspect drug were collected, and 776 preferred terms signals involving 27 system organ classes were identified. The main affected groups were females and individuals between 18 and 45 years of age. Psychiatric disorders and nervous system disorders were the most common adverse reactions. The analysis also revealed some adverse reactions not recorded in the manual, including cardiovascular risk, such as pancreatitis, increased chylomicron, hyperchylomicronemia, and myocardial reperfusion injury, as well as rare but serious adverse reactions like neuroleptic malignant syndrome and anosognosia. Conclusions: This study identified new cardiovascular risks associated with olanzapine, including pancreatitis and myocardial reperfusion injury, which require further investigation.

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Objective: To examine the effect of nutritional counseling therapy (NCT) combined with transcranial direct current stimulation (tDCS) on binge eating disorder (BED) symptoms. Methods: Forty women with BED were randomly allocated (2:2:2 ratio) to one of the following groups: active tDCS (a-tDCS), NCT, sham tDCS (s-tDCS) with NCT, and a-tDCS with NCT. Home-based tDCS was applied to the dorsolateral prefrontal cortex for 28 sessions. Results: A mixed analysis of variance (ANOVA) showed no main effect between groups nor a time × group interaction. However, a significant main effect was found for time on the primary outcome Binge Eating Scale (BES) (p = 0.001; eta2p = 0.325), which tended to decrease during treatment and follow-up. A significant main effect was found for the secondary outcome short-interval intracortical inhibition (SICI) (p = 0.02; eta2p = 0.112), a measure of inhibitory function, which increased from baseline to the final period in the a-tDCS group, without significant differences between groups. Conclusion: Combined NCT and tDCS did not have a synergistic effect on BED symptoms. Nevertheless, the data from this pilot study should help plan future larger-scale studies investigating the effects of tDCS and behavioral interventions in the promising area of BED treatment. Clinical trial registration: ClinicalTrials.gov: NCT 04226794. Registered on July 2, 2019.

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Objective: Recent studies have revealed a heterogeneous prevalence and presentation of post-traumatic stress disorder across countries. It is crucial to assess the methodological and item-level measurement factors that contribute to variations in mental disorder rates across cultures. This study aimed to investigate the traumatic experiences of hospital workers by employing item analysis of the Impact of Event Scale-Revised. Methods: Data were collected from 1,000 employees of a large hospital during the coronavirus disease 2019 pandemic and were analyzed according to item response theory analysis regarding item pool discrimination (a) and difficulty (b) parameters. Results: The Impact of Event Scale-Revised items had good discriminative ability (a) and covered a range of distress severity (b) associated with traumatic experiences. According to our results, the Impact of Event Scale-Revised is a reliable and informative instrument for assessing individuals with moderate to severe trauma-related distress across the spectrum of trauma symptoms. In particular, items 10 (“jumpy or easily startled”) and 6 (“I thought about it when I didn’t mean to”) reflected the post-traumatic stress disorder domains of hyperarousal and intrusion and excelled in discriminating between different levels of post-traumatic distress. Conversely, items related to avoidance and sleep disturbance showed lower discriminative ability. Conclusions: Item analysis of the Impact of Event Scale-Revised may be used to assess trauma symptoms in the context of a trauma exposure, identifying the most discriminative and informative items for measuring post-traumatic stress disorder in our context. Our findings may help refine the Impact of Event Scale-Revised and facilitate the development of a more effective scale with optimized item parameters.

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Objective: Due to the uncertainty whether atypical and typical antipsychotics have a stronger association with mortality among older people with schizophrenia, we examined the rates and causes of mortality in older adults with schizophrenia who take atypical or typical antipsychotics. Methods: In a 5-year prospective multicenter study of patients aged ≥ 55 years with an ICD-10 diagnosis of schizophrenia, we used a multivariable logistic regression model to examine the association between atypical vs. typical antipsychotics and mortality, adjusting for sociodemographic and clinical characteristics. Results: Of 313 older adults with schizophrenia, the 5-year all-cause mortality rates in patients who took atypical (n=192) and typical (n=167) antipsychotics were 36.4% and 24.3%, respectively. Following adjustment, no significant differences were found in all-cause mortality (AOR = 1.56; 95%CI 0.75-3.27; p = 0.24) or causes of mortality (all p > 0.05) between medication groups. Atypical antipsychotics were significantly associated with lower overall mortality in the subpopulation with baseline Mini Mental State Examination scores < 24 (AOR = 0.24; 95%CI 0.07-0.84; p = 0.025). Conclusion: Although atypical antipsychotics may not be associated with lower odds of overall mortality than typical antipsychotics in older people with schizophrenia, they might be associated with lower mortality among those with substantial cognitive impairment.

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Objective: There has been a call for neuroscientific studies of spiritual experiences due to their global prevalence, significant impact, and importance for understanding the mind-brain problem. Mediumship is a spiritual experience where individuals claim to communicate with or be influenced by deceased persons or non-material entities. We assessed whether mediums carry specific genetic alterations. Methods: We selected highly gifted mediums (n=54) with over 10 years of experience who engaged in mediumistic work for no material gain, performed whole-exome sequencing of these individuals, and compared its findings to those of first-degree relatives who claimed no mediumship (n=53). Results: We identified 15,669 variants exclusively found in mediums, likely to impact the function of 7,269 genes. Thirty-three of these genes were altered in at least one-third of all mediums but in none of their relatives. The inflammatory pathway was the most frequently affected (43.9%), with the translocation of zeta-chain associated protein kinase 70 kDa (ZAP-70) to the immunological synapse being particularly prominent. Conclusion: This is the first exome-wide investigation of genes possibly related to mediumistic experiences. We identified gene variants that were present in mediums but not in their non-medium first-degree relatives. These genes emerge as possible candidates for further investigations of the biological underpinnings that allow spiritual experiences such as mediumship.

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Objective: Major depressive disorder is heterogeneous. While transcranial direct current stimulation (tDCS) is an effective treatment, its impact on symptoms remains underexplored. This ancillary study investigated the effects of home-use tDCS on depression symptom clusters. Methods: Data were used from the Portable Transcranial Electrical Stimulation and Internet-Based Behavioral Therapy for Major Depression Study (PSYLECT) study, in which 210 depressed patients were randomized to active (n=137) or sham tDCS (n=73) for 6 weeks. Items from the Hamilton Depression Rating Scale were grouped into symptom clusters using hierarchical clustering. Treatment effects were analyzed with mixed regressions. An alternative clustering solution was also evaluated using a larger sample. Results: Four clusters were identified: emotional, sleep, psychomotor, and psychosomatic symptoms. None showed significant group differences (sleep: p = 0.058, Cohen’s d = 0.36, emotional: p = 0.976, d = -0.01, psychosomatic: p = 0.157, d = 0.27, psychomotor: p = 0.944, d = 0.01). The alternative clustering solution produced a similar sleep cluster, where tDCS led to significant reductions (p = 0.033, d = 0.41), but no differences were observed in other clusters (emotional: p = 0.707, d = 0.07, atypical: p = 0.537, d = 0.12). Conclusion: The association between tDCS and sleep improvement warrants further study. tDCS may be more effective for specific symptom clusters.

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Objective: Bipolar disorder (BD) involves complex mood, neuropsychological, immunological, and physiological changes, with cognitive impairment persisting even during remission. Our study investigated the relationship between the second-to-fourth digit ratio (2D:4D) and cognitive function in BD patients. Methods: This cross-sectional study, which included 47 BD patients in remission for ≥ 6 months and 47 healthy volunteers, was designed to thoroughly determine the relationship between the 2D:4D and cognitive function in BD. The Stroop Test, the Wisconsin Card Sorting Test, and the Trail Making Test A and B forms were administered to all participants. The same researcher measured the 2D:4D ratio using a digital caliper to ensure consistency and accuracy. Results: The left 2D:4D ratio was significantly higher in the patient group than the control group. There were also significant differences in all test scores between groups, with the BD group scoring higher and being more unsuccessful. We also observed a weak negative correlation between completion time of Form A of the Trail Making Test and right-hand 2D:4D finger ratio in the BD group. Conclusions: Our findings have significant implications, revealing a marked difference in the 2D:4D of BD patients compared to healthy controls and a decline in cognitive function even during remission.

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Objective: To determine clusters (groups) of substance use in crack cocaine users through severity scores on the sixth version of the Addiction Severity Index (ASI-6) and compare the groups in relation to risk factors, such as parental style, childhood maltreatment, and impulsivity. Methods: This cross-sectional study included 531 men with substance use disorder who were admitted to an inpatient addiction treatment unit in southern Brazil. To detect more homogeneous groups of individuals, the K-means clustering based on ASI-6 scores was used to create groups of individuals with similar severity scores in different areas. Parenting styles were assessed using the Measure of Parental Style, childhood trauma was assessed using the Childhood Trauma Questionnaire, and impulsivity was measured using the Barratt Impulsivity Scale 11. Poisson regression was used for association analysis. Results: Two distinct clusters were identified, which differed significantly across all composite scores (p < 0.001). These associations were further confirmed through Poisson regression analysis. The more severe cluster showed significantly higher scores for maternal abuse (p = 0.026), sexual abuse (p = 0.003), motor impulsivity (p = 0.014), and unplanned impulsivity above the 75th percentile (p = 0.032) than the less severe group. Other parenting styles, trauma types, and impulsivity did not differ significantly between the groups. Conclusion: Dividing patients into severity clusters can contribute to more targeted treatments. Further research on outpatients would reinforce the importance of early life factors and impulsivity treatment.

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Objective: Cannabis is the most widely used substance in Brazil. This study examined subtypes of individuals who use cannabis based on usage characteristics and correlates with use of other substances and harms. Methods: Data are from the São Paulo Megacity Mental Health Survey (n=5,037). Latent class analysis (LCA) was performed considering age of onset, use frequency, tobacco consumption, heavy episodic drinking (HED), alcohol use disorder (AUD), and substance use disorder. Logistic regression assessed class correlates, and a further analysis compared sociodemographic, health, and behavioral indicators. Results: A four-class model was optimal for 496 individuals. The Polydrug class (26.2%) and the Former class (5.9%) showed earlier onset and highest frequency of cannabis use, with strongest harm associations. The Polydrug class had higher odds of other drug use (OR = 3.0), tobacco use (OR = 2.5), HED (OR = 1.8), and AUD (OR = 1.5), compared to lighter-use groups. About 30% of those who use cannabis are at increased risk for negative outcomes, particularly those with early, frequent, and polydrug use patterns. Conclusion: Brazil’s public health should prioritize targeted prevention of the risks associated with early and frequent cannabis and polydrug use. Addressing this at-risk group is essential for harm reduction and a health-focused approach.

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Objective: Post-stroke depression affects approximately 40% of stroke survivors, with cognitive deficits being frequently observed. Transcranial direct current stimulation (tDCS) has shown promise in improving cognitive performance in stroke patients. We explored the effects of tDCS on cognitive performance in post-stroke depression. Methods: We conducted an exploratory analysis of 48 patients from a double-blinded, sham-controlled, randomized clinical trial that investigated the effects of tDCS on post-stroke depression. A neuropsychological battery was applied at baseline and endpoint. We assessed three key domains: 1) the Stroop effect, measured with Stroop Test components (the color-naming, word-reading, and word-color interference tasks); 2) processing speed, measured with the Trail Making Test and the Digit Symbol-Coding task; 3) executive function, assessed with the Digit Span test and the Frontal Assessment Battery. Linear mixed regression models were used to evaluate group-wise changes. Results: We found that executive function worsened slightly in the active tDCS group and improved in the sham group in the adjusted models. Significant interactions were also found for the Frontal Assessment Battery. Conclusions: We found no consistent evidence that tDCS significantly improved cognitive domains. The bidirectional association with cognition analysis suggests that the effects of tDCS may vary based on depression severity and task complexity. Clinical trial registration: NCT01525524

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Objective: Ultra-high risk criteria were developed to identify prodromal symptoms of psychosis, although the transition does not occur in most individuals. This highlights the need to identify transition markers, such as movement analysis. In the first stage of our study, movement analysis was used to differentiate controls from ultra-high risk patients, who had reduced movement and increased erraticism. We aimed to determine whether these variables can predict ultra-high risk outcomes after follow-up. Methods: Ultra-high risk individuals were recorded while performing two speech tasks at baseline. The videos were analyzed using motion energy analysis for head and torso movements (mean amplitude, frequency, and variability) and were manually coded for gesticulation. During follow-up, seven participants transitioned to psychosis, 21 to other DSM-5 disorders (called the general disorder group), and 18 did not transition to psychosis. Results: The general disorders group showed lower torso frequency and higher variability in both regions than the psychosis group, as well as greater torso variability than the non-transition group. No differences were found between the psychosis and non-transition groups. Gesticulation did not significantly differ between groups. Conclusions: Baseline movement variability distinguishes ultra-high risk transition outcomes, with higher variability in those who transitioned to non-psychotic disorders. This demonstrates the importance of movement analysis as a potential transition marker and suggests that treating ultra-high risk individuals as a single group may overlook important information.

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Objective: To examine changes in plasma brain-derived neurotrophic factor (BDNF) levels in patients undergoing electroconvulsive therapy or magnetic seizure therapy, as well as any early or late variations in BDNF. Specific changes related to each technique were also evaluated. Methods: We measured plasma BDNF before and throughout treatment in adult patients (18 to 65 years old) diagnosed with treatment-resistant depression who underwent convulsive therapy (electroconvulsive therapy or magnetic seizure therapy) in the ElectroMagnetic Convulsive therapy for DEpression (EMCODE) project. Results: We enrolled 31 participants (mean age = 38.4 years, SD = 11.88), of whom 14 (45.16%) underwent electroconvulsive therapy and 17 (54.84%) underwent magnetic seizure therapy. Notable improvements in depressive symptoms were observed in both groups, with no significant differences between them (p = 0.1046). However, no significant changes in plasma BDNF levels were observed for either technique pre- or post-treatment (mean difference = -93.01 pg/mL, 95%CI 545.88-359.86) or over time (coefficient = -67.95, standard error = 37.75, p = 0.072). Conclusions: The findings suggest that no significant changes occurred in plasma BDNF levels following convulsive therapy, which challenges the notion that BDNF is a biomarker for treatment-resistant depression.

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Objective: Sleep quality is essential for health, and sleep deprivation is linked to physical and mental issues. Homeless populations face additional sleep challenges, yet this topic remains underexplored. This study assessed sleep quality among homeless individuals in São Paulo, Brazil, considering demographics and substance use. Methods: A psychiatrist conducted interviews to collect demographic and substance use data assessing sleep quality using the Pittsburgh Sleep Quality Index (PSQI). A generalized linear model was used to analyze PSQI scores, considering sleeping location, sex, substance use, and interactions as fixed factors, with homelessness duration as a covariate. The sample comprised 177 participants (22% female, of whom seven were transgender; mean age: 42.8 ± 11.4 years), with an average homelessness duration of 10.5 (SD, 8.4) years (range: 1-40). Among them, 33% slept in shelters, 83% used depressants, 83% used stimulants, and 59% used hallucinogens. Results: Approximately 67% reported good subjective sleep quality (mean PSQI: 4.9 ± 2.7). Depressant and stimulant use correlated with poorer sleep. Women had poorer sleep, longer sleep latency, and greater daytime dysfunction than men. Conclusion: Positive sleep quality reports may reflect adaptive expectations from prolonged adversity and substance use. The findings highlight the need for improved shelters and targeted interventions to address sleep challenges in this vulnerable population.

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Objective: This study examined the effects of socioeconomic status as a possible moderator of the effects of family conflict on externalizing/internalizing behavior and hippocampal and amygdala volume. Methods: A longitudinal complete-case analysis of 714 children and adolescents (mean age: 11.2 years; 46.2% female) was conducted using data from the Brazilian High-Risk Cohort Study for Psychiatric Disorders in Childhood. At baseline, parents/guardians completed the Family Environment Scale and a socioeconomic status scale. Three years after baseline assessment, the same participants underwent brain magnetic resonance imaging, and the Child Behavior Checklist was administered. Automated segmentation of the amygdala and hippocampus was performed in FreeSurfer 5.1. Results: Although family conflict at baseline predicted externalizing/internalizing behavior at follow-up, we found no evidence that family conflict and socioeconomic status affected brain structure or that family conflict had a moderating effect on psychopathology and brain outcomes conditioned on socioeconomic status. Conclusion: These results are consistent with emerging evidence that family conflict is a risk factor for externalizing/internalizing behavior in youth. These findings warrant further attention, focusing on prevention and intervention efforts and social policy development.

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Objective: Flourishing, a holistic concept encompassing multiple domains of well-being, has gained significant interest in recent years. However, validated tools for measuring flourishing, mainly using VanderWeele’s framework, remain unavailable for Brazilian Portuguese-speaking populations. This article describes the translation into Brazilian Portuguese, cross-cultural adaptation, and validation of the resulting versions of the Flourishing Index (FI) and Secure Flourishing Index (SFI). Methods: The instruments were translated and adapted following international guidelines for cross-cultural adaptation of self-report measures. In Study 1, psychometric properties were examined using exploratory factor analysis (EFA) in a general-population sample (n=359). Construct validity was assessed by correlating FI/SFI scores with quality of life, depression, anxiety, and posttraumatic growth. In Study 2, confirmatory factor analysis (CFA) was conducted in a sample of individuals with moderate depressive symptoms (n=252) to confirm the factor structure. Reliability and validity were evaluated in both samples. Results: EFA identified a five-factor structure for the FI and a six-factor structure for the SFI, consistent with prior studies. Cronbach’s alpha ranged from 0.60 to 0.86, supporting internal consistency. CFA confirmed the multidimensional structures with appropriate fit indices (root-mean-square error of approximation [RMSEA] < 0.08, standardized root-mean-square residual [SRMR] < 0.08). Construct validity analyses demonstrated significant correlations between FI/SFI and mental health, quality of life, and posttraumatic growth. Conclusion: The Brazilian Portuguese versions of the FI and SFI demonstrated appropriate psychometric properties, enabling comprehensive assessments of flourishing in diverse contexts. These validated tools can now be used to support flourishing research and intervention evaluation in Brazil.

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Objective: Paraphilias, atypical sexual preferences outside societal norms, present a psychiatric challenge. The DSM-5-TR differentiates paraphilic fantasies (PFs) from disorders, with the latter causing distress or impairment. Social stigma and underreporting hinder understanding. This study examines PF and disorders in Brazil, focusing on pedophilia and hebephilia, to inform public health policies and crime prevention. Methods: This cross-sectional, online study included 5,335 Brazilian participants. The survey collected sociodemographic data and applied the Paraphilic Assessment Protocol, adapted from the Dunkelfeld Project, to assess fantasies, temporal criteria, and distress or impairment. Results: Most respondents (62.2%) reported three or more PFs, with masochism (64.4%), body part fetishism (58%), and sadism (49.2%) being most common. Nonconsensual fantasies included pedophilia (3.7%), hebephilia (6.6%), frotteurism (7.5%), and exhibitionism (6.8%). Pedophilic and hebephilic disorders were found in 1.87 and 2.46% of participants, respectively, and were associated with young age (18-24 years), cisgender male identity, bisexual orientation, and single marital status. Notably, working in healthcare and education was associated with these disorders. Conclusion: As Brazil’s first nationwide survey on paraphilias, this study underscores the need for targeted interventions to prevent sexual crimes and improve treatment options. Further research is essential despite ongoing stigma.

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Objective: Brain default mode network (DMN) function is altered in schizophrenia (SZ). Considering the roles of nitrergic and glutamatergic transmission in SZ neurobiology, supplementation with nitric oxide (NO) donors such as sodium nitroprusside (SNP) has been proposed as a means of reducing symptoms, but results have been mixed and potential mechanisms remain unclear. In this context, we sought to investigate the effects of SNP on DMN functional connectivity (FC) assessed by functional magnetic resonance imaging (fMRI) in SZ patients and healthy controls. Methods: In an open-label trial, participants were divided into three treatment groups to receive intravenous SNP (0.25 μg/kg/min over 12 minutes): SZ patients on clozapine (CLZ) (n=13), SZ patients on non-CLZ antipsychotics (n=13), and controls (n=14). fMRI data was collected continuously before, during, and after SNP infusion. Symptom changes were evaluated with the Brief Psychiatric Rating Scale (BPRS). Results: Considering only patient groups at baseline, there was no difference in connectivity. When comparing all patient groups to controls, patients exhibited increased activity in DMN subregions and increased FC in the left supramarginal gyrus. During SNP infusion, FC was increased in the left angular gyrus; immediately following infusion, FC increased in the bilateral medial temporal gyri and left supramarginal gyrus of patients compared to controls. There were no significant differences between patient groups at any time point, nor changes in symptoms. Conclusion: Although our results are preliminary, this work demonstrated for the first time that SNP modulates brain connectivity in healthy controls and patients with SZ. Future research is warranted to confirm these findings.

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Objective: This study aimed to identify young adults who met the criteria for bipolar disorder (BD) but had not yet been diagnosed or treated. It also aimed to evaluate their neurocognitive and neurobiological changes compared to healthy controls (HC). Methods: Individuals at high risk for BD were identified by using the Hypomania Checklist 32 items (HCL-32R). Participants were then assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to identify previously undiagnosed and drug-naive patients (DNP) (n=27). A matched HC group (n=27) was included for comparison. All participants completed a cognitive battery assessing executive function, attention, working memory, and verbal learning. Magnetic resonance imaging (MRI) was used to assess cortical thickness. Oxidative stress markers – including thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), and the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) – were measured. Results: The DNP group underperformed across all the tests administered but group differences were significant in the Wisconsin Card Sorting Test (WCST) and Rey Auditory Verbal Learning Test (RVALT). Among oxidative stress markers, only CAT levels were significantly higher in the DNP group. Additionally, patients exhibited significant cortical thinning in several brain regions. Conclusion: Neurobiological alterations and neurocognitive dysfunction are present in the early-stage, unmedicated stages of BD. However, longitudinal studies are needed to better understand the progression of these changes.

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Objective: To determine whether there are differences in the parameters triglyceride glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI), and metabolic score index for insulin resistance (METS-IR) between subgroups of patients diagnosed with bipolar disorder (BD) – in euthymic, manic, and depressive states – and healthy controls. Methods: A total of 238 patients diagnosed with BD and 90 healthy controls were included in the study. Results: TyG-BMI was higher in depressed-state BD patients than in manic-state BD patients. The METS-IR was significantly higher in depressed BD patients than in healthy controls. TyG-BMI was a statistically significant predictor of euthymic and depressed states of BD. In addition, the METS-IR was a statistically significant predictor of euthymic-state BD, depressed-state BD, and BD overall. In the receiver operating characteristic (ROC) analysis, we obtained the highest area under the ROC curve (AUC) values in the parameters TyG-BMI and METS-IR to discriminate the patient groups from healthy controls. Conclusion: This is the first study to provide evidence that elevated levels of METS-IR and TyG-BMI may be an indicator of IR in BD patients and can be used to differentiate BD patients from healthy controls. However, there is a need for confirmation of these results in larger studies before definitive conclusions can be drawn.

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Objective: To investigate, using functional magnetic resonance imaging (fMRI) techniques, the immediate and sustained effects of acupuncture on functional connectivity (FC) within the default mode network (DMN) and external FC. Methods: Thirty healthy participants received acupuncture needle stimulation at Baihui (GV20) and Yintang (GV29) and underwent resting-state fMRI scans in three phases: pre-needle insertion, during needle retention, and post-needle removal. Each phase lasted 20 minutes. Results: In terms of within-network connectivity of the DMN, post-needle removal scans showed a decrease in FC between the medial prefrontal cortex (mPFC) and the angular gyrus (ANG) compared to pre-needle insertion scans. The FC analysis from seed points to whole-brain voxels showed the following changes: compared to pre-needle insertion scans, acupuncture needle insertion increased the FC between the posterior cingulate cortex/precuneus (PCC/PCU) and Cerebellum_8_L; acupuncture needle withdrawal increased the FC between the PCC/PCU and Cerebellum_8_L; acupuncture needle insertion decreased the FC between ANG and Frontal_Sup_Medial_L; and acupuncture needle withdrawal decreased the FC between ANG and Frontal_Sup_Medial_L. Conclusion: These results suggested that acupuncture has an impact on the DMN and that these effects are sustained, not just immediate.

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Objective: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are cytokines that play critical roles in the maturation, homeostasis, and differentiation of B-cells. Both cytokines have also been associated with mental disorders. The link between inflammation and depression is well-established. Patients undergoing hemodialysis who also experience depressive symptoms exhibit a state of immune dysfunction. We hypothesized that BAFF and APRIL levels would influence future depressive symptoms in hemodialysis patients. Methods: We enrolled 72 hemodialysis patients without baseline depressive symptoms. Depressive symptoms were assessed annually for 2 years using the Beck Depression Inventory-II. The participants were measured for plasma BAFF, APRIL, and tumor necrosis factor-α levels. To evaluate the impact of these levels on the development of depressive symptoms, we performed Cox regression and Kaplan-Meier analysis. Results: Depressive symptoms were observed in 31 (43.1%) patients. In both univariate and multivariate Cox regression analyses, a 1 SD increase in BAFF was significantly associated with an increased risk of future depressive symptoms, with hazard ratios of 1.44 (95%CI 1.03-2.00) and 1.70 (95%CI 1.04-2.78), respectively. Higher BAFF groups had a significantly greater incidence of depressive symptoms over 2 years (p = 0.048). Conclusion: Elevated plasma BAFF levels were significantly associated with the development of depressive symptoms in hemodialysis patients.

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Objective: The COVID-19 pandemic affected public health worldwide. Binge drinking is a high-risk behavior pattern linked to health problems and injuries. We aimed to assess the prevalence of binge drinking at four time points during the 1st year of the pandemic and correlate these with sociodemographic variables, providing insights into binge drinking trends. Methods: This cross-sectional study analyzed data from a national survey conducted between April 2020 and January 2021 with 11,205 adult participants. Sociodemographic variables included sex, age, sexual orientation, race, education level, and health care worker status. Regression models were used to assess associations with past-month binge drinking, which was the dependent variable. Results: Binge drinking rates were stable across the four time points. Male sex was consistently associated with binge drinking at all time-points. Other variables such as younger age, lower educational background, and non-straight sexual orientation were associated with binge drinking at some, but not all, time points. Conclusion: The persistence of gender disparities in binge drinking during a period of high unprecedented stress suggests the need for targeted interventions in future public health emergencies. Further research is required to explore the pandemic’s long-term effects on alcohol consumption behaviors and related health outcomes.

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Social anxiety disorder (SAD), one of the most prevalent anxiety disorders, is not well recognized. In most cases, SAD follows an unremitted and chronic course, affecting individual functioning in relationships, education, and work. Due to the disorder’s relevance in Brazil, guideline-based treatments adapted to the Brazilian social and economic context are needed. We conducted a systematic review assessing several treatment modalities for SAD. PubMed, Cochrane, SciELO, and ClinicalTrials.gov were searched using the Medical Subject Headings social anxiety disorder and social phobia. Of the 438 selected articles, 20 were selected. Selective serotonin reuptake inhibitors are considered a first-line treatment for SAD due to their large effect size and database of evidence. Monoamine oxidase inhibitors, benzodiazepines, and the anticonvulsants pregabalin and gabapentin are also effective. Divergent results have been found for the serotonin-norepinephrine reuptake inhibitor venlafaxine. Among psychological interventions, robust data support cognitive behavioral therapy (whether individual, group, or remote) as a first-line option. Psychodynamic psychotherapy, exposure and social skills therapy, self-help therapies (with or without support), cognitive bias modification, virtual reality exposure therapy, and mindfulness-based therapy are also effective techniques. Psychological interventions are better tolerated and there is evidence that they provide better long-term benefits than pharmacological agents. Access to treatment (considering the Brazilian socioeconomic context), treatment adherence, short and long-term response rates, and side effects must be considered when choosing the best treatment strategy.

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Clinical staging models are tools used in healthcare that have the potential to enhance diagnostic precision, improve treatment decisions, articulate more personalized care pathways, and optimize service models. In youth mental health, clinical staging has been increasingly applied to conditions where progression from non-specific symptoms to full-blown syndromes, such as schizophrenia, bipolar disorder, and depression, is possible. However, novel transdiagnostic staging models have also been proposed, recognizing the limitations of current classification systems and the substantial overlap of symptoms, particularly early in the illness course. Models incorporating an appropriate developmental and transdiagnostic lens may offer significant advances for research and clinical practice, supporting early intervention and secondary prevention. This narrative review critically examines theoretical premises and empirical applications of transdiagnostic clinical staging models in youth. Peer-reviewed studies were identified in PubMed using search terms related to clinical staging, focusing on sociodemographic, cognitive, and clinical factors investigated in youth samples (age 12-30 years). Evidence is synthesized in three main sections: progression, extension, and stage-based treatment. Additionally, a stage-based care model and directions for future research are presented. Early findings partially support important assumptions for the model, suggesting stage-related differences in cognition and functionality. Furthermore, new extension features have been recently proposed, including substance use, circadian disturbances, and physical illnesses. The long-term outcomes of stage-based interventions remain an open question. While the transdiagnostic clinical staging model offers a promising alternative for classifying youth psychopathology, further empirical validation is essential before its widespread implementation.

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Digital therapeutics have evolved rapidly with technological advances in healthcare. Despite their increasing use, gaps remain in understanding their regulatory frameworks, integration, and efficacy for conditions like substance use disorder, insomnia, attention deficit hyperactivity disorder, and post-traumatic stress disorder. This study evaluates U.S. Food and Drug Administration (FDA)-approved digital therapeutics and explores their potential to revolutionize psychiatric treatments amid ongoing technological and regulatory changes. We conducted a comprehensive review of major databases, focusing on articles published until January 2024 about FDA-approved digital therapeutics. We excluded non-English articles, those lacking empirical data, and those focusing on non-FDA-approved therapeutics. Our analysis covered regulatory compliance, clinical outcomes, and integration with traditional treatments. A review of nine FDA-cleared digital therapeutics revealed benefits, such as improved treatment accessibility and potential reductions in healthcare costs. For example, through Somryst, a cognitive-behavioral therapy-based treatment for insomnia, over 40% of users overcame chronic insomnia, and 60% experienced improvements without adverse effects. However, challenges remain, including low provider adoption, inadequate insurance coverage, and high user dropout rates. While digital therapeutics enhance accessibility, they face regulatory challenges, reimbursement issues, and require robust clinical evidence. Success depends on collaboration among stakeholders to demonstrate value, ensure safety, and integrate them into existing healthcare systems.

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Objective: Depression is a common and debilitating disorder affecting millions of people. First-line treatments fail to achieve remission in approximately one-third of patients, highlighting a critical need for treatment. Transcranial direct current stimulation (tDCS) has emerged as a novel treatment for depression. Therefore, the aim of this review was to provide a comprehensive overview of the last decade of tDCS trials for depression and to suggest future research directions. Methods: To synthesize studies from the past decade, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) of tDCS for depression. Results: A total of 21 RCTs were included, showing a moderate effect of active tDCS compared to placebo. We also provided a description of study designs, stimulation parameters, and patient characteristics. We then proposed possible strategies to improve clinical efficacy and reduce outcome variability, including 1) optimization/personalization of tDCS through spatial and temporal target localization, 2) optimized methodological strategies, including home-based, accelerated tDCS protocols and novel study designs, and 3) investigation of the patient profile to identify characteristics that may predict treatment response. Conclusion: tDCS shows promise as a treatment for depression, but variability in study parameters and outcomes underscores the need for further optimization. Refinement and standardization of protocols may improve its efficacy.

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Objective: Emotions affect health and health affects emotions. When properly recognized and interpreted, emotions can aid in the prevention, diagnosis, and treatment of many diseases. Affective computing, the use of computer technology to detect one or more signals associated with human emotions, is a promising field. However, research into the use of emotion recognition in healthcare remains scarce. It is crucial to explore the reasons behind this phenomenon and identify neglected methods with potential for human health. We review methods and technologies used in emotion recognition and their applications in healthcare, highlighting methods not discussed in previous reviews, including electroencephalography and electrocardiography, thermal imaging, bracelets, skin conductance, and audio. Methods: A metric based on reproducibility and population was established to assess the quality of included articles. Based on the metrics established, we surveyed and analyzed studies in which affective computing tools were applied to health, to qualify and identify the challenges of the area. Results: We found many challenges to be overcome in detecting and recognizing human emotions, related to sample size, low study quality, and reproducibility issues. We list and discuss the main current challenges, ways to overcome them, and perspectives for the future, focusing on the application of affective technologies in healthcare and the establishment of a gold standard. Conclusion: Three suggestions are proposed: 1) to conduct studies focused on obtaining a gold standard; 2) to conduct studies with larger sample sizes, greater diversity, and in less controlled environments, using replicable methodologies and making data and methods available; and 3) to further explore the potential use of emotion detection in healthcare.

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Objective: This meta-analysis aimed to evaluate the efficacy of naltrexone-bupropion in binge eating disorder patients. Methods: We searched MEDLINE, Embase, and Cochrane databases up to February 2025 for randomized controlled trials comparing naltrexone-bupropion to placebo. The primary outcome was binge eating frequency. Secondary outcomes included body mass index, body weight, depression, lipid profile, and glycated hemoglobin levels. Mean differences (MD) with 95%CI were pooled using appropriate methods. Results: Three trials were included with a total of 177 patients, of whom 49% received the intervention. There was no significant difference between groups for binge eating (MD -1.25; 95%CI -5.61 to 3.11; 0 = 0.57), body mass index (MD -2.24; 95%CI -8.01 to 3.53; p = 0.45), depression (MD -0.81; 95%CI -3.48 to 1.87; p = 0.55), or total cholesterol (MD -9.98; 95%CI -21.31 to 3.34; p = 0.15). A potential benefit was observed in glycated hemoglobin levels (MD -0.10; 95%CI -0.28 to 0.08; p = 0.26). Conclusion: This meta-analysis found that naltrexone-bupropion has no significant benefits over placebo in reducing binge eating episodes or in improving metabolic or psychological outcomes. The possible effect on glycated hemoglobin levels warrants further investigation. Systematic review registration: PROSPERO CRD420250651559

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Objective: Vascular cognitive impairment (VCI) is a major cause of cognitive decline associated with vascular brain injury. Behavioral and psychological symptoms of dementia (BPSD) are common, but their prevalence across VCI subtypes remains unclear. This study examines the prevalence of BPSD in different VCI subtypes. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Studies assessing BPSD in patients with VCI were retrieved from PubMed, Embase, and Web of Science. Studies were eligible if they used the Neuropsychiatric Inventory (NPI) to evaluate symptoms. Pooled prevalence rates for each NPI domain were calculated using a random-effects model. Results: Thirty-five studies (n=5,805) were included. In unspecified VCI, apathy (54.29%), depression (43.48%), and irritability (38.76%) were most common. Subcortical VCI was associated with higher apathy (62.01%), depression (52.11%), and irritability (44.73%). Mixed dementia featured increased apathy (61.65%), depression (45.68%), sleep disturbances (44.63%), and more hallucinations (26.64%). VCI non-dementia (VCI-ND) was associated with depression (44.97%), irritability (32.75%), and anxiety (30.07%). Conclusion: BPSD are prevalent across VCI subtypes but vary. Mixed dementia features more hallucinations and sleep disturbances, likely due to overlapping vascular and neurodegenerative pathology. Apathy and agitation in subcortical VCI may reflect vascular burden. Further research is warranted to clarify underlying neurobiological mechanisms. Systematic review registration: PROSPERO CRD42024587171

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Objective: Patients at risk of psychosis present a variety of symptoms, and identifying the most discriminative symptoms is essential for efficient detection and treatment. Methods: This cross-sectional online study analyzed individuals from the general population to better assess their risk of symptoms classified as clinical high risk (CHR) for psychosis. The 16-item Prodromal Questionnaire was applied as a self-report screening tool. Item response theory with a graded response model was used to assess the discrimination and difficulty of the questionnaire’s criteria. Results: The analysis included 936 participants (mean age: 21.5 years; 71.9% women). “Déjà vu” stood out for its high discriminative power, while the “voices or whispers” and “seeing things” items had greater precision than the other CHR-related symptoms. Conversely, the “smell or taste” and “changing faces” items were associated with the most severe cases. Conclusion: This study identified the most indicative CHR-related symptoms for accurate assessment of psychosis severity, which can be used to guide targeted preventative interventions.

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Objective: To evaluate whether attitudes toward drug use, as well as decision-making, communication, and alcohol resistance skills, act as predictors of alcohol use and binge drinking initiation among Brazilian students, considering sex differences. Methods: In a longitudinal sample of 1,103 seventh-grade students from 15 Brazilian public schools, we explored if attitudes toward drug use and decision-making, communication, and alcohol resistance skills at baseline predicted alcohol outcomes 9 months later. Results: Lower levels of resistance skills (i.e., ORboys = 0.29; 95%CI 0.12-0.70) and positive attitudes toward drugs (i.e., ORgirls: = 1.41; 95%CI 1.02-1.94) were predictors of alcohol use onset and binge drinking, independently of sex. Decision-making predicted binge drinking initiation, but only for girls (OR = 0.73; 95%CI 0.59-0.91). Negative attitudes toward drugs were a risk factor for alcohol use initiation, but only for boys (OR = 0.78; 95%CI 0.64-0.95). Conclusion: Our findings highlight the importance of understanding the predictors of alcohol initiation in adolescents, to inform which key components preventive programs should address in their activities to achieve the expected preventive outcomes.

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Objective: To systematically review studies on schizophrenia in Brazil, addressing geographical coverage as an indicator of sampling representativeness – an essential precondition for inferences regarding the generalizability of findings – and, secondarily, of variation in research funding across different regions. Methods: We searched for studies carried out until July 2023. The inclusion criteria were studies of patients diagnosed with schizophrenia (or its spectrum) recruited in Brazil. The following parameters were extracted: geographic region of the first and last authors, recruitment setting, research subfield, and funding sources. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of 296 studies reviewed, most (63.18%) took place in the Southeast region, particularly the state of São Paulo (48.98%). Clinical trials comprised the majority (41.6%); genetic studies were primarily conducted in the Southeast or South (81.5%). Funding was reported in 64% of papers. The Northeast region was less likely to receive study funding compared to the Southeast. Conclusion: Schizophrenia research in Brazil shows a clear geographic concentration, with significant disparities in funding allocation and underrepresentation of certain regions. Broadening research coverage through equitable distribution of funding opportunities and fostering collaborations with local institutions are of utmost importance to enhance the understanding and treatment of schizophrenia within Brazil’s diverse socioeconomic and ethnic landscape.

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Objective: Major depressive disorder (MDD) is a leading cause of disability among youth, yet identifying this condition remains challenging. Naturalistic communication offers a promising approach to enhance depression detection. Increased use of first-person singular pronouns (e.g., “I”) has been linked to MDD, but its applicability to younger, non-English-speaking populations remains unclear. Methods: This study examined first-person pronoun use in Brazilian Portuguese-speaking adolescents with and without MDD and its relationship to self-reported and clinician-rated depressive symptoms. Fifty-two adolescents (13 with and 39 without MDD) from the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo) sample completed remote data collection using a WhatsApp chatbot, responding to questions via audio recordings. Transcripts were analyzed using the Linguistic Inquiry and Word Count (LIWC). Results: The MDD group used significantly more I-pronouns than non-MDD subjects (9.15 vs. 8.02%, t = -2.302, p = 0.026). Self-reported depressive symptomatology correlated with I-pronoun use (rho = 0.366, p = 0.008), but did not reach statistical significance for clinician-rated symptoms (rho = 0.248, p = 0.076). Conclusions: These findings support first-person singular pronouns as a potential linguistic marker of depression among Brazilian adolescents. This is the first study to replicate such results in a young, non-English-speaking sample using spoken speech, suggesting that integrating linguistic analysis with digital tools could enhance early detection efforts, particularly in resource-limited settings. Future research should explore use of I-pronouns alongside other linguistic and acoustic features to refine digital mental health screening approaches.

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Objective: This study analyzed the role of vaccination in preventing COVID-19-related mortality in patients with schizophrenia. Methods: This retrospective cohort study analyzed data from the Influenza Epidemiological Surveillance Information System (Sistema de Informação da Vigilância Epidemiológica da Gripe [SIVEP-Gripe]) database, focusing on patients aged ≥ 18 years with laboratory-confirmed COVID-19 between February 2020 and February 2023. The primary exposure was schizophrenia. The primary outcome of interest was the role of vaccines in preventing COVID-19-associated mortality. Statistical analysis included multiple binary logistic regressions to determine the impact of schizophrenia on mortality and to compare vaccine protection between cohorts. Results: The cohort included 2,131,089 patients, 3,516 (0.2%) of whom had schizophrenia. After adjusting for potential confounders, patients with schizophrenia presented a significantly higher risk of severe disease (OR = 1.59, 95%CI 1.39-1.81) and mortality (OR = 1.65, 95%CI 1.45-1.87). After the booster dose, protection against mortality was estimated at 67.7% (95%CI 66.5-68.7) in the non-schizophrenia cohort and 62.4% (95%CI 44.1-74.6) in the schizophrenia cohort. Mortality rate differences of approximately 20% and 10% were observed between boosted and non-vaccinated individuals among the schizophrenia and non-schizophrenia cohorts, respectively. Consequently, five patients (95%CI 4-8) with schizophrenia and 10 patients (95%CI 9-11) in the general population would need to receive a booster dose to prevent one fatality. Conclusions: Our results suggest that vaccination provided similar protection against COVID-19-related mortality in individuals with and without schizophrenia. However, the magnitude of the intervention effect was double for individuals with schizophrenia due to their higher baseline risk.