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Alexandre Faisal-Cury,1 Karen M Tabb,2 Guilherme Niciunovas,3 Carrie Cunningham,4 Paulo R Menezes,1 Hsiang Huang4,5 1Department of Preventive Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil; 2School of Social Work, University of Illinois at Urbana-Champaign, Urbana, IL, USA; 3School of Medicine, Federal University of São Paulo, São Paulo, Brazil; 4Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA; 5Department of Psychiatry, Laboratory of Psychopathology and Psychiatric Therapeutics (LIM-23), Faculty of Medicine, University of São Paulo, São Paulo, Brazil Abstract: Adolescent pregnancy has social, economic, and educational consequences and is also linked to adverse perinatal outcomes. However, studies show a positive relationship between pregnancy and increased social status among low-income adolescents. This study aims to assess the association between planned pregnancy and years of schooling among low-income Brazilian adolescents. This is a secondary analysis of a cohort study conducted from May 2005 to March 2007 in public primary care clinics in São Paulo, Brazil. Participants (n=168) completed a detailed structured questionnaire. Logistic regression was used to examine the association between years of schooling and planned pregnancy. After adjusting for the covariates income, wealth score, crowding, age, marital status, and race, planned pregnancy was independently associated with lower years of education (odds ratio: 1.82; 95% confidence interval: 1.02–3.23). Although this finding may be related to these adolescents having less access to information and health services, another possible explanation is that they have a greater desire to have children during adolescence. Keywords: adolescent pregnancy, planned pregnancy, Brazil, low-income population, women

Na medida em que a população mundial está envelhecendo, a demência está se constituindo em importante problema de saúde pública, particularmente nos países em desenvolvimento. Investigações epidemiológicas nestes países são escassas e apresentam dificuldades metodológicas adicionais, principalmente no que se refere à adequação sociocultural dos instrumentos utilizados para a definição de casos. Tendo em vista estas preocupações, foi fundado o "Grupo de Pesquisa em Demência 10/66", que é constituído por uma rede internacional de pesquisadores, predominantemente de países em desenvolvimento. O nome do grupo tem como referência o paradoxo de que menos de 10% dos estudos populacionais sobre demência são dirigidos aos 2/3 ou mais de casos de pessoas com demência que vivem em países em desenvolvimento. O objetivo do artigo é atualizar informações da literatura sobre as diferenças de prevalência e incidência de demência encontradas em países desenvolvidos e em desenvolvimento.

Background: Anemia and dementia are common diseases among the elderly, but conflicting data are available regarding an association between these two conditions. We analyzed data from the São Paulo Ageing & Health Study to address the relationship between anemia and dementia.Methods: This cross-sectional observational study included participants aged 65 years and older from a deprived area of the borough of Butantan, São Paulo, Brazil. Data about demographics, education, income, and cognitive and daily life function were collected, as well as blood samples. Anemia and dementia were defined according to WHO and DSM-IV criteria, respectively.Results: Of the 2267 subjects meeting the inclusion criteria, 2072 agreed to participate in the study; of whom 1948 had a valid total blood count and were included in the analysis. Anemia was diagnosed in 203 (10.2%) participants and dementia in 99 (5.1%). The frequency of anemia was higher in patients with dementia according to univariate analysis (odds ratio (OR) = 2.00, 95% confidence interval (CI) = 1.17-3.41, p = 0.01), but this association was not present after adjusting for age (OR = 1.33, 95% CI = 0.76-2.33, p = 0.32). Further multivariate adjustment did not change the results.Conclusion: Although anemia and dementia are frequent disorders in older people, we found their relationship to be mediated exclusively by aging in this low-income population from São Paulo. [ABSTRACT FROM AUTHOR]

Background: Dementia is now a major public health issue in low- and middle-income countries, and strategies for primary prevention are needed. This study aimed to estimate the proportion of cases of dementia attributable to illiteracy, non-skilled occupation and low income, which are common, potentially modifiable social adversities that occur along the lifespan in low- and middle-income countries.Methods: This report is based on data from the São Paulo Ageing & Health Study (SPAH) study (N = 2003). All individuals aged 65 years and older residing within pre-defined socially deprived areas of the city of São Paulo, Brazil, were included. The outcome of interest was prevalent dementia. Indicators of socioeconomic position (SEP) were literacy (distal indicator), highest occupational attainment (intermediate indicator), and monthly personal income (proximal indicator). We estimated the proportion of prevalent dementia attributable to each SEP indicator (illiteracy, non-skilled occupations and low income) by calculating their population attributable fractions (PAF).Results: Dementia was more prevalent amongst participants who were illiterate, had non-skilled occupations and lower income. Illiteracy, poor occupational achievement and low income accounted for 22.0%, 38.5% and 38.5% of the cases of dementia, respectively. There was a cumulative effect of socioeconomic adversities during the lifespan, and nearly 50% of the prevalence of dementia could be potentially attributed to the combination of two or three of the socioeconomic adversities investigated.Conclusions: Public policies aimed at improving education, occupational skills and income could potentially have a role in primary prevention of dementia. Governments should address this issue in a purposeful and systematic way. [ABSTRACT FROM AUTHOR]

AIMS: To estimate the prevalence of cannabis use in the last 12 months in the Brazilian population and to examine its association with individual and geographic characteristics. DESIGN: Cross-sectional survey with a national probabilistic sample. PARTICIPANTS: 3006 individuals aged 14 to 65 years. MEASUREMENTS: Questionnaire based on well established instruments, adapted to the Brazilian population. FINDINGS: The 12-month prevalence of cannabis use was 2.1% (95%CI 1.3-2.9). Male gender, better educational level, unemployment and living in the regions South and Southeast were independently associated with higher 12-month prevalence of cannabis use. CONCLUSION: While the prevalence of cannabis use in Brazil is lower than in many countries, the profile of those who are more likely to have used it is similar. Educational and prevention policies should be focused on specific population groups. [ABSTRACT FROM AUTHOR]

We describe a cross-sectional survey to identify risk factors for colonisation of neonates by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae. This occurred following exposure to a colonised healthcare worker during an outbreak in an intermediate-risk neonatal unit. In total, 120 neonates admitted consecutively during a three-month period were screened for ESBL-producing K. pneumoniae by rectal swabbing and 27 were identified as colonised. Multivariate analysis showed colonisation to be independently associated with use of antibiotics and absence of breastfeeding. Previous use of antibiotics presented an odds ratio (OR) of 12.3 [95% confidence interval (CI): 3.66-41.2, P<0.001]. The most commonly used antibiotics were penicillin and amikacin. Breastfeeding was associated with reduced risk for colonisation (OR: 0.22; 95% CI: 0.05-0.99; P=0.049). Nine isolates recovered during the first stage of the outbreak and 27 isolates from surveillance cultures were typed thereafter by pulsed-field gel electrophoresis, revealing six different profiles (A-F). Clones A, C, and E were implicated in the first stage of the outbreak, whereas among the 27 strains recovered from surveillance cultures, all six clones were identified. Clone A was also found on the hand of a nursing auxiliary with onychomycosis. We concluded that prior antimicrobial use predisposed to colonisation. The possible role of breastfeeding as a protective factor needs to be further elucidated. Detection of different genotypes of ESBL-producing K. pneumoniae suggests that dissemination of mobile genetic elements bearing the ESBL gene may have been superimposed on the simple dissemination of a clone during the outbreak. [ABSTRACT FROM AUTHOR]

Background: This study examined the validity of the self-reporting questionnaire (SRQ-20) in a population-based survey with older adults in Sao Paulo, Brazil.Method: The study sample consisted of 2,008 individuals aged 65 years or more who were living in an economically disadvantaged area of the city. The geriatric mental state (GMS) was used as the gold standard for the assessment of common mental disorders (CMD).Results: The optimal SRQ-20 threshold for case definition was 4/5 (sensitivity = 76.1%, specificity = 74.6%, area under ROC curve = 0.82). Women, older participants and those with lower income were more likely to be misclassified by the questionnaire. The inclusion of older persons with dementia or psychosis did not change the ability of the SRQ-20 to identify cases of CMD.Discussion: The SRQ-20 may be a useful instrument to be used in large epidemiological studies in resource-poor settings for the identification of cases of depression and anxiety in later life. The performance of the SRQ-20 among older adults was similar to that observed with the adult population in Brazil. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the prevalence of dementia in a socioeconomically disadvantaged population of older adults living in the city of São Paulo, Brazil.Methods: A cross-sectional one-phase population-based study was carried out among all residents aged > or = 65 in defined census sectors of an economically disadvantaged area of São Paulo. Identification of cases of dementia followed the protocol developed by the 10/66 Dementia Research Group.Results: Of 2072 individuals in the study, 105 met the criteria for a diagnosis of dementia, yielding a prevalence of 5.1%. Prevalence increased with age for both men and women after age 75 years, but was stable from 65 to 74 years. Low education and income were associated with increased risk of dementia.Conclusions: The prevalence of dementia among older adults from low socioeconomic backgrounds is high. This may be partly due to adverse socioeconomic conditions and consequent failure to compress morbidity into the latter stages of life. The increasing survival of poorer older adults with dementia living in developing countries may lead to a rapid increase in the prevalence of dementia worldwide. [ABSTRACT FROM AUTHOR]

Background: 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region.Methods: 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality.Findings: Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24.3 million people have dementia today, with 4.6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81.1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours.Interpretation: We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources. [ABSTRACT FROM AUTHOR]

Objectives: To establish whether the risk of psychotic disorders in cannabis users changes with time following cannabis cessation using data from the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) case-control study., Methods: The EU-GEI case-control study collected data from first episode psychosis patients and population controls across sites in Europe and Brazil between May 2010 and April 2015. Adjusted logistic regressions were applied to examine whether the odd of psychosis case status changed: (1) with time following cannabis cessation and (2) across different cannabis use groups., Results: Psychosis risk declined following cessation of cannabis use (β = -0.002; 95% CI -0.004 to 0.000; P  = 0.067). When accounting for duration of use, this effect remained (β = -0.003; 95% CI -0.005 to -0.001; P  = 0.013). However, in models adjusting for frequency and potency of use the result was not significant. Analysis of different cannabis use groups indicated that ex-users who stopped 1 to 4 weeks previously had the highest risk for psychotic disorder compared to never users (OR = 6.89; 95% CI 3.91-12.14; P  < 0.001); risk declined for those who stopped 5 to 12 weeks previously (OR = 2.70; 95% CI 1.73-4.21; P  < 0.001) and 13 to 36 weeks previously (OR = 1.53; 95% CI 1.00-2.33; P  = 0.050). Ex-users who stopped 37 to 96 weeks (OR = 1.01; 95% CI 0.66-1.57; P  = 0.949), 97 to 180 weeks (OR = 0.73; 95% CI 0.45-1.19; P  = 0.204), and 181 weeks previously or more (OR = 1.18; 95% CI 0.76-1.83; P  = 0.456) had similar psychosis risk to those who had never-used cannabis., Conclusion: Risk of psychotic disorder appears to decline with time following cannabis cessation, receding to that of those who have never used cannabis after 37 weeks or more of abstinence. Although, preliminary results suggest that frequent users of high potency types of cannabis might maintain an elevated risk compared to never users even when abstaining for longer than 181 weeks., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MDF reports personal fees from Janssen, outside the submitted work. RMM reports personal fees from Janssen, Lundbeck, Sunovion, and Otsuka, outside of the submitted work. CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. The other authors have no conflicts of interest to declare.

Background: Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls., Methods: We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables., Results: FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123-2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368-0.997 and OR = 0.646, CI 0.457-0.913 respectively) and JTC bias (OR = 0.625, CI 0.422-0.925 and OR = 0.602, CI 0.460-0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297-2.578, FRP deficits (OR = 1.393, CI 1.031-1.882, and JTC (OR = 1.661, CI 1.271-2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups., Conclusions: Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.

Background: Suicide is a global health concern whose rates are soaring in many low-and-middle-income countries. Public awareness campaigns have been implemented in Brazil; however, their impact is uncertain., Methods: This was an ecological study using population data from DATA-SUS, a Brazilian official notification system, selecting only deaths that were voluntarily self-inflicted (CID-10 × 60-X84). We analyzed all available data from 2000 to 2019 to assess trends before and after the national Yellow September (YS) campaign started in 2015. Differences in trends were assessed by Joinpoint Analysis (JA) and Regression Discontinuity Analysis (RDD), unadjusted and adjusted for economic factors., Results: Overall, there was a progressive increase in the rate of relative (per 100,000 inhabitants) number of suicides over time between 2000 and 2019 (57 % increase). The JA detected a change in the slope of the curve representing an acceleration in suicides starting in the year 2015. Adjusted RDD revealed the year that Yellow September started significantly change the slope of the association between time and rates of suicide (p interaction  < 0.01), and marginal analysis detected the coefficient increased from 0.07 (95%CI 0.04-0.10) to 0.27 (95%CI -0.07-0.60) suicides/year per 100,000 inhabitants., Limitations: The ecological nature of the manuscript compromises causational implications., Conclusions: We found an increase in suicidal trends in Brazil, against the global trend that coincides with the beginning of a large national awareness campaign. Although we cannot attribute causality, our results reinforce the need of further studies to better understand the role of awareness campaigns in suicide reduction interventions, including potential unintended effects., Competing Interests: Declaration of competing interest Rodolfo Furlan Damiano: Declares no conflict of Interest Loren Beiram: Declares no conflict of Interest Bianca Besteti Fernandes: Declares no conflict of Interest Maurício Scopel Hoffmann: Declares no conflict of Interest Alexander Moreira-Almeida: Declares no conflict of Interest Christian Rück: Declares no conflict of Interest Hermano Tavares: Declares no conflict of Interest André R. Brunoni: Declares no conflict of Interest Euripedes Constantino Miguel: Declares no conflict of Interest Paulo Rossi Menezes: Declares no conflict of Interest Giovanni Abrahão Salum: Declares no conflict of InterestAcknowledgements We acknowledge Daniela Lopes Ângelo for helping to do the first statistical analysis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = -0.34, 95% CI = [-0.660, -0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity., (© 2024. The Author(s).)

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure., (© 2024. The Author(s).)

Objective: The objective was to identify validated instruments from the literature that assess the mental health of police officers., Methods: This is a systematic review of validated instruments used to assess the mental health of police officers. Searches were conducted in the MEDLINE, Web of Science, Scopus, Embase, CINAHL/EBSCO, and Virtual Health Library databases. This review follows the JBI Manual for Systematic Reviews and the PRISMA statement. The methodological quality of the articles and the risk of bias were assessed., Results: A total of 1530 studies were identified across the six databases, with 158 studies read in full by the authors after excluding duplicates and those that did not meet the inclusion criteria. The final 29 studies were analyzed for methodological quality and risk of bias using the AXIS and SFS-D tools., Conclusion: This review identified 27 self-administered validated instruments useful for assessing various mental health outcomes in police officers, with the most frequently used being the Police Stress Questionnaire. These findings may help guide security force administration, occupational health professionals, and mental health researchers in selecting and implementing psychometrically reliable instruments for screening the mental health of police officers.

Background and Hypothesis: Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings., Study Design: We used incidence data in people aged 18-64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group., Study Results: Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61-0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55-0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02-2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings., Conclusions: Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Introduction: Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP., Methods: In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach., Results: In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation., Conclusions: This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis., Limitations: Cross-sectional study design, self-reported questionnaires., Competing Interests: Declaration of competing interest A. Lok is a member of the suicide advisory board of Jansen. C. Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. M. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. M. Di Forte has received honoraria for educational lectures from Recordati, Janssen and Lumbech. PM. Llorca has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of Boehringer-Ingelheim, Eisai, Ethypharm, Janssen-Cilag, Lundbeck, Neuraxpharm, Otsuka, Rovi., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is limited evidence as to whether the immune protein profile is associated with a particular symptomatology pattern across the psychosis continuum ., Methods: We estimated two bifactor models of general and specific dimensions of psychotic experiences in unaffected siblings of patients ( n = 52) and community controls ( n = 200), and of psychotic symptoms in first-episode psychosis (FEP) patients ( n = 110). We evaluated associations between these transdiagnostic dimensions and trait (TNF- α , IFN- γ ), state (IL-6, IL-1 β ), and regulatory (TGF- β , IL-10, IL-4) cytokines. We explored whether schizophrenia genetic liability (schizophrenia polygenic risk score; SZ-PRS) modified the associations., Results: High levels of trait marker IFN- γ were associated with the severity of general psychosis dimension in the unaffected siblings and community controls, expanding to the depressive dimension in siblings and to the manic dimension in FEP. High TNF- α levels were associated with more positive psychotic experiences in unaffected siblings and manic symptoms in FEP. Low levels of state markers IL-6 and IL-1 β were observed in unaffected siblings presenting more depressive experiences. Still, high levels of IL-6 and IL-1 β were associated with the severity of the depressive and negative symptom dimensions at FEP. The severity of transdiagnostic dimension scores across the three groups was associated with lower regulatory cytokines. Exploratory analysis suggested that a high SZ-PRS contributed mostly to associations with psychotic dimensions., Conclusions: IFN- γ mapped onto the multidimensional expression of psychosis, reinforcing the trait concept. State markers IL-6 and IL-1 β may fluctuate along the spectrum. Dysfunction in the regulatory arm may disinhibit the inflammatory system. Associations with psychotic dimensions may be more prone to SZ-PRS susceptibility.

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To ascertain whether sociodemographic and health-related characteristics known from previous research to have a substantive impact on recovery from depression modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO)., Methods: The CONEMO study consisted of two randomized controlled trials, one conducted in Lima, Peru, and one in São Paulo, Brazil. As a secondary trial plan analysis, mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest defined by characteristics measured before randomization - suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension - in both trials. We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models., Results: Increased effects of the CONEMO intervention on the primary outcome (reduction of at least 50% in depressive symptom scores at 3-month follow-up) were observed among older and wealthier participants in the Lima trial (p = 0.030 and p = 0.001, respectively)., Conclusion: There was no evidence of such differential effects in São Paulo, and no evidence of impact of any other secondary outcomes in either trial., Clinical Trial Registration: NCT02846662 (São Paulo, Brazil - SP), NCT03026426 (Lima, Peru - LI)., Competing Interests: The authors report no conflicts of interest.

Importance: Depression is a leading cause of disability worldwide, and there is increasing interest in nonpharmacological treatments. Auricular acupuncture (AA) is a simple, low-cost, and well-tolerated option, but further studies are needed to establish its efficacy and safety., Objective: To estimate the efficacy and safety of auricular acupuncture as a treatment for depression., Design, Setting, and Participants: This randomized clinical trial was conducted at 4 university research centers in Brazil, from March to July 2023. Eligible patients were adults aged 18 to 50 years whose score on the Patient Health Questionnaire-9 (PHQ-9) indicated moderate depression (score 10-14) or moderately severe depression (score 15-19). Exclusion criteria included previous application of AA, risk of suicidal ideation, or severe depression (PHQ-9 score >20). An intent-to-treat analysis and modified intent-to-treat analysis were conducted., Intervention: Participants were randomized into 2 treatment groups, which included specific AA (SA) and nonspecific AA (NSA). Both groups received 12 sessions of AA with semipermanent needles with daily stimulation twice a week over 6 weeks and were followed-up for 3 months. All participants continued with their usual care for ethical reasons. The SA group's treatment protocol consisted of 6 acupuncture points on the auricular pavilion chosen according to the diagnosis of depression by traditional Chinese medicine (Shenmen, subcortex, heart, lung, liver, and kidney). The NSA group's acupuncture points were the external ear, the cheek and face area, and 4 nonspecific points in the helix region unassociated with mental health symptoms. A locator device was used to confirm which areas had neuroreactive points., Main Outcomes and Measures: The primary outcome was a reduction of at least 50% in the PHQ-9 score (ie, depression recovery) at 3 months. Secondary outcomes included depression recovery at 4 and 6 weeks; depression remission (PHQ-9 score < 5) at 4 weeks, 6 weeks, and 3 months); and adverse events., Results: A total of 304 participants were screened, and 74 participants (62 women [84%]; median [IQR] age, 29 [23-27] years) were included in the intention-to-treat analysis, with 37 participants randomized to each group (SA and NSA). A total of 47 participants (64%) were followed-up through 3 months. The results showed no statistically significant difference in depressive recovery between the groups at 3 months (14 of 24 participants in the SA group [58%] vs 10 of 23 participants in the NSA group [43%]; risk ratio [RR], 1.34; 95% CI, 0.76-2.45; P = .38). The proportions of depression recovery and remission at 4 and 6 weeks based on the PHQ-9 were higher in the SA group (except for depression recovery at 6 weeks) with no statistically significant differences. However, a statistically significant difference was observed in symptom remission at 3 months (11 of 24 participants in the SA group [46%] vs 3 of 23 participants in the NSA group [13%]; RR, 1.99; 95% CI, 1.16-3.34; P = .02) in favor of SA. There were no significant differences in adverse event rates between the groups, evidencing the intervention's safety. Most participants reported mild pain at the needle application site (33 patients [94%] in the SA group vs 32 patients [91%] in the NSA group). Five participants dropped out of the study due to adverse events., Conclusions and Relevance: The results of this randomized clinical trial suggest that SA over 6 weeks is safe. Although there was no statistically significant difference between groups for the primary efficacy outcome, patients receiving SA did experience greater symptom remission at 3 months. A larger sample size and longer intervention are needed to further evaluate the efficacy of SA for depression., Trial Registration: ClinicalTrials.gov Identifier: NCT05855421.

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood., (© 2023. The Author(s).)

Background: Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP., Methods: We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP., Findings: Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries., Interpretation: Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Religiosity and spirituality (R/S) have been negatively associated with several mental health problems, including delinquency. The study aimed to investigate the relationship between R/S and interpersonal violence using a systematic review., Methods: We conducted a descriptive systematic review followed by meta-analyses using seven different databases. We included observational studies that assessed the relationship between R/S and different types of interpersonal violence (physical and sexual aggression and domestic violence)., Results: A total of 16,599 articles were screened in the databases and, after applying the eligibility criteria, 67 were included in the systematic review and 43 were included in the meta-analysis. The results showed that higher levels of R/S were significantly associated with decreased physical and sexual aggression, but not domestic violence. All selected studies evidenced sufficient methodological quality, with 26.8% being cohort studies. In the subanalyses, the role of R/S was more prevalent among adolescents., Conclusion: There is an inverse relationship between R/S and physical and sexual aggression, suggesting a protective role. However, these results were not observed for domestic violence. Healthcare professionals and managers should be aware of their patients' beliefs when investigating interpersonal violence to create tailored interventions for reducing violent behavior., Competing Interests: The authors report no conflicts of interest.

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., Competing Interests: GPR has received honoraria for lectures and/or advisory panel membership from Janssen, Lundbeck, Otsuka, and Sunovion, and a research grant from Sunovion. The other authors report no conflicts of interest..

Abtract: Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = <0.001; abuse: OR = 2.16; p < 0.001; neglect: OR = 2.27; p = <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p < 8.1 × 10 -8 ). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p < 5 × 10 -5 ) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone., Methods: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR) exposure and PRS - OR exposure - OR PRS + 1] with adjustment for potential confounders., Results: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88)., Conclusions: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

5-aminolevulinic acid (5-ALA) is the first precursor of the heme biosynthesis pathway, accumulated in acute intermittent porphyria (AIP), an inherited metabolic disease characterized by porphobilinogen deaminase deficiency. An increased incidence of hepatocellular carcinoma (HCC) has been reported as a long-term manifestation in symptomatic AIP patients. 5-ALA is an α-aminoketone prone to oxidation, yielding reactive oxygen species and 4,5-dioxovaleric acid. A high concentration of 5-ALA presents deleterious pro-oxidant potential. It can induce apoptosis, DNA damage, mitochondrial dysfunction, and altered expression of carcinogenesis-related proteins. Several hypotheses of the increased risk of HCC rely on the harmful effect of elevated 5-ALA in the liver of AIP patients, which could promote a pro-carcinogenic environment. We investigated the global transcriptional changes and perturbed molecular pathways in HepG2 cells following exposure to 5-ALA 25 mM for 2 h and 24 h using DNA microarray. Distinct transcriptome profiles were observed. 5-ALA '25 mM-2h' upregulated 10 genes associated with oxidative stress response and carcinogenesis. Enrichment analysis of differentially expressed genes by KEGG, Reactome, MetaCore™, and Gene Ontology, showed that 5-ALA '25 mM-24h' enriched pathways involved in drug detoxification, oxidative stress, DNA damage, cell death/survival, cell cycle, and mitochondria dysfunction corroborating the pro-oxidant properties of 5-ALA. Furthermore, our results disclosed other possible processes such as senescence, immune responses, endoplasmic reticulum stress, and also some putative effectors, such as sequestosome, osteopontin, and lon peptidase 1. This study provided additional knowledge about molecular mechanisms of 5-ALA toxicity which is essential to a deeper understanding of AIP and HCC pathophysiology. Furthermore, our findings can contribute to improving the efficacy of current therapies and the development of novel biomarkers and targets for diagnosis, prognosis, and therapeutic strategies for AHP/AIP and associated HCC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Hypothesis: It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries., Study Design: We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity., Study Results: Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (ranges AUROC  = 0.84-0.86). Specificity (range = 73.9-78.0%) and sensitivity (range = 75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands., Conclusions: The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability., Competing Interests: R.M.M. has received honoraria from Janssen, Sunovian, Lundbeck and Otsuka. M.B. has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. Other authors declare that they have no conflict of interest. All other authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)