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Objective: Some months after the remission of acute COVID-19, some individuals show depressive symptoms, which are predicted by increased peak body temperature (PBT) and decreased blood oxygen saturation (SpO2). The present study aimed to examine data on whether long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes during the acute infectious and long COVID phases. Methods: This case-control, retrospective cohort study used the Homeostasis Model Assessment 2 (HOMA2) calculator© to compute β-cell function (HOMA2%B) and insulin sensitivity (HOMA2%S) and resistance (HOMA2-IR) and administered the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) to 86 patients with long COVID and 39 controls. Results: Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose (FBG), and insulin levels; 33.7% of the patients vs. 0% of the controls had HOMA2-IR values > 1.8, suggesting IR. Increased IR was predicted by PBT during acute infection and associated with depressive symptoms above and beyond the effects of NIO pathways (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3] inflammasome, myeloperoxidase [MPO], protein oxidation). There were no significant associations between increased IR and the activated NIO pathways during long COVID. Conclusion: Long COVID is associated with new-onset IR, which may contribute to onset of depressive symptoms due to long COVID by enhancing overall neurotoxicity.

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Objective: Mortality rate is a general indicator which can be used to measure care and management of schizophrenia. This cohort study evaluated the standardized mortality ratios (SMRs) of all-cause mortality and life-years lost (LYLs) in patients with schizophrenia under a community care program in China. Methods: Data were obtained from the National Community Care Program System for Severe Mental Disorders. A total of 99,214 patients diagnosed with schizophrenia were enrolled before December 2014 and followed between 2015 and 2019. A total of 9,483 patients died. Crude mortality rates (CMRs) and SMRs were then stratified by natural vs. unnatural causes, and major groups of death were standardized according to the 2010 National Population SMRs. The corresponding LYLs at birth were also calculated by gender and age. Results: The SMRs of patients with schizophrenia were significantly elevated during the study period, with an overall SMR of 4.98 (95%CI 2.67-7.32). Neoplasms, cardiovascular diseases, cerebrovascular diseases, external injuries, and poisonings were the most significant causes of death among patients with schizophrenia compared to the general population. The mean LYLs of patients with schizophrenia were 15.28 (95%CI 13.26-17.30). Males with schizophrenia lost 15.82 life-years (95%CI 13.48-18.16), and females lost 14.59 life-years (95%CI 13.12-16.06). Conclusions: Patients with schizophrenia under community care had a high mortality rate in our study, even though mental health services have been integrated into the general healthcare system in China to narrow treatment gaps in mental health for > 10 years. In terms of mortality outcome indicators, effective and quality mental health services still have a long way to go. The current study demonstrates the potential for improved prevention and treatment of individuals with schizophrenia under community care.

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Objectives: Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma. Methods: Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software. Results: Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis. Conclusion: Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.

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Objectives: This study investigated behavioral self-regulation problems using the Children’s Hostility Inventory (CHI) in pediatric bipolar disorder (PBD), healthy offspring of bipolar disorder patients (HOBD), and healthy controls (HC) without previous history of psychiatric disorders. Methods: The CHI was administered to 41 consecutive children and adolescents diagnosed with PBD, to 16 HOBD, and to 22 HC. The inventory assessed irritability, expression, hostility, and aggression and was completed by the children with the help of their mothers. Adolescents and their respective parents were interviewed separately using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Results: All subscales of the CHI presented statistically significant differences, except for the subscale assessing feelings of suspicion. Pairwise comparisons revealed consistently significant differences between the PBD group and controls, indicating more self-regulation difficulties in the PBD group, represented by high levels of hostility and aggressive behavior. There were no significant differences between the PBD and HOBD groups. Conclusions: Future studies should further investigate if such behavior is state-dependent or a trait of bipolar juvenile expression. Expression of hostility and irritability should be considered relevant targets in psychosocial approaches addressing this population.

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Objective: The Identifying Depression Early in Adolescence Risk Score (IDEA-RS) was recently developed in Brazil using data from the Pelotas 1993 Birth Cohort to estimate the individualized probability of developing depression in adolescence. This model includes 11 sociodemographic variables and has been assessed in longitudinal studies from four other countries. We aimed to test the performance of IDEA-RS in an independent, community-based, school-attending sample within the same country: the Brazilian High-Risk Cohort. Methods: Standard external validation, refitted, and case mix-corrected models were used to predict depression among 1442 youth followed from a mean age of 13.5 years at baseline to 17.7 years at follow-up, using probabilities calculated with IDEA-RS coefficients. Results: The area under the curve was 0.65 for standard external validation, 0.70 for the case mix-corrected model, and 0.69 for the refitted model, with discrimination consistently above chance for predicting depression in the new dataset. There was some degree of miscalibration, corrected by model refitting (calibration-in-the-large reduced from 0.77 to 0). Conclusion: IDEA-RS was able to parse individuals with higher or lower probability of developing depression beyond chance in an independent Brazilian sample. Further steps should include model improvements and additional studies in populations with high levels of subclinical symptoms to improve clinical decision making.

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Objective: To examine the association between urbanization and psychological well-being (PWB) in China. Methods: Data were obtained from the 2015 China Health and Nutrition Survey (CHNS) and included 3,071 men and 3,385 women aged 50 years or older who lived in 288 communities across 12 provinces and municipalities. The urbanization index, which summarizes 12 urbanization dimensions at community level, was categorized into tertiles representing low, medium, and high levels of urbanization. PWB was assessed by scoring three self-reported questions. Gender-stratified multilevel analyses were used to estimate the association between urbanization and PWB. Results: After controlling for individual-level factors, the urbanization index was associated positively with PWB. More specifically, an increase of one SD in the score of community population density, economic activity, housing, education, sanitation, or diversity was associated significantly with PWB in both genders. In addition, increases in the score of community communications, social services, transportation, or modern markets were associated significantly with PWB in women, but not in men. Conclusion: Urbanization has, on average, had an independent and positive effect on PWB in middle-aged and older Chinese populations, with many components of urbanization being separately and positively associated with PWB, especially in women.

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Objectives: The impact of climate change on mental health is well established, but few studies have examined the perspectives of young people, especially in low- and middle-income countries (LMICs). In this qualitative study, we explored how Brazilian children and adolescents experience climate change. This approach can help inform environmental education, communication, and self-care strategies for this age group. Methods: We conducted focus groups with 50 children and adolescents aged 5 to 18 years in three locations in Brazil. We analyzed the data using an interpretative phenomenological analysis framework. Results: We identified three profiles of involvement with climate change: unaware, disengaged, and engaged. Profiles were largely related to different socioeconomic contexts. We analyzed each profile across the dimensions of space, time, emotions, and actions. Adults were portrayed by participants as stubborn deniers, as neutral influences, or as role models of knowledge and engagement. Due to their age and developmental level, young children had distinctive perceptions of climate change. Conclusion: Spatial and temporal perceptions of climate change are a key element for experiencing and engaging with environmental concerns and vary according to age and socioeconomic differences. Effective communication to foster climate action at individual and collective levels requires narratives that reach different ages. Replication of these findings in other LMICs is warranted.

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Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

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Alcohol and other substance use disorders are complex problems with multiple variables and determinants, requiring a multidimensional approach to prevention and treatment. A robust body of research shows that religiosity and spirituality (R/S) play a prominent role in these disorders; however, how to apply this knowledge remains unclear. We present practical guidelines on how to integrate R/S into substance use prevention and treatment in an ethical, evidence-based manner. These guidelines have been endorsed by prominent academic leaders in these topics and by health associations affiliated with the three major Brazilian religions. The integration of R/S is part of a respectful, person-centered, interdisciplinary approach, which imposes neither religious beliefs nor secular worldviews. The most critical interventions include collecting a history of spiritual and religious beliefs, practices, and experiences and evaluating how these may be used positively in treatment. It is also essential that health professionals are encouraged to value and respect the R/S of patients, and that religious groups recognize that professional and technical interventions can make a valuable contribution to preventing and treating these disorders.

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Objectives: We assessed the efficacy of cognitive behavioral therapy and bupropion compared to cognitive behavioral therapy alone for methamphetamine use disorder. Methods: The selection criteria for this systematic review study with meta-analysis were randomized clinical trials on the efficacy of cognitive behavioral therapy and bupropion in the treatment for methamphetamine use disorder (assessed by urine metabolites). The search was conducted in PubMed, PubMed Central, LILACS, SciELO, Cochrane Library, SCOPUS, Google Scholar, Ovid Medline, Clinicaltrials.gov, and the International Clinical Trials Registry Platform. The primary outcome was relapse. Risk of bias was assessed with the RoB 2 tool. The results of each clinical trial were input into an Excel spreadsheet. We performed a meta-analysis using relative risk and a 95%CI. Results: Of the 597 initial articles (498 after removing duplicate records), five were included in the meta-analysis, with an aggregate sample of 539 patients. An overall relative risk of 0.91 (95%CI 0.78-1.05) was estimated for relapse. Conclusion: Our study limitations included publication bias and heterogeneous populations. We found no evidence that cognitive behavioral therapy and bupropion reduced the risk of relapse compared to cognitive behavioral therapy and placebo.

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Objective: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer’s disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD. Methods: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood. Results: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral blood. The kynurenine-to-tryptophan ratio was only increased in peripheral blood of the AD group. 3-Hydroxykynurenine was decreased only in cerebrospinal fluid and showed higher variability in the CN group than the AD group. Kynurenic acid was increased in cerebrospinal fluid and decreased in peripheral blood. Finally, there were no changes in kynurenine and quinolinic acid between the groups. Conclusions: Our results suggested a shift toward the kynurenine pathway in both the brain and in the periphery, as well as a shift towards increased kynurenic acid production in the brain but decreased production in peripheral blood. In addition, our analysis indicated dissociation between the central and peripheral levels, as well as between plasma and serum for some of these metabolites. Finally, changes in the kynurenine pathway are suggested to be a core component of AD. More studies are warranted to verify and consolidate our results.