Gene-environment interactions increase psychosis risk (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657). However, identifying the genetic variants involved and how they interact with environmental risk factors underlying psychosis remains challenging.

To investigate whether there are gene-environment interactions in the relationships of childhood trauma, lifetime cannabis use, and single nucleotide variants (SNVs) of dopamine D2 receptor (D2R: DRD2), N-methyl-d-aspartate receptor (NMDAR: GRIN1, GRIN2A and GRIN2B) and cannabinoid receptor type 1 (CB1R: CNR1) with psychosis.

In a population-based case-control study nested in an incident study (STREAM, Brazil) (Del-Ben et al. Br J of Psychiatry 2019; 215(6):726-729), part of the EU-GEI consortium (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657), 143 first-episode psychosis patients and 286 community-based controls of both sexes aged between 16 and 64 years were included over a period of 3 years. Twenty-three SNVs of D2R (rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip. Environmental adversities were evaluated using the Cannabis Experience Questionnaire (Di Forti et al. The Lancet Psychiatry 2009; 6(5):427–436) and the Childhood Trauma Questionnaire (Grassi-Oliveira et al. Rev Saude Publica 2006; 40(2):249-55). Associations between SNVs and environmental risk factors were performed using the nonparametric multifactor dimensionality reduction software (version 3.0.2).

Single locus analysis showed no association among the 23 SNVs with psychosis; however, gene-environment analysis was significant for the polymorphic loci rs12720071 and rs7766029 in CNR1. The best association models were the two-factor representing by the combination of CNR1 rs12720071 with lifetime cannabis use (p<0.001), and CNR1 rs12720071 with childhood trauma (p<0.05), both suggesting an increased risk of psychosis. Additionally, when considering the interaction of both environmental factors in the same model, we found CNR1 rs7766029 to be associated with psychosis (p<0.001).

Our study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs (rs12720071 and rs7766029), childhood trauma and lifetime cannabis use in psychosis.

None Declared

Neuroanatomical abnormalities are reported in psychotic disorders compared to healthy controls; nevertheless, less is known about the role of familial liability to psychosis in morphological brain changes.

Using an exploratory voxel-based morphometry (VBM) analyses of the whole brain, we evaluated differences on GMVs across the whole brain among first-episode psychosis (FEP) patients, community-controls, and healthy siblings of patients to interrogate the role of familial liability.

Data were retrieved from a study (STREAM) conducted in Ribeirão Preto/SP Brazil. We included 71 first-episode psychosis patients (67.6% males, mean age±SD: 18.7±10.8), 24 unaffected siblings of patients (37.5% males, mean age±SD 30.8±10), and 36 controls (71.9% males, mean age±SD: 10±10.5). All magnetic resonance imaging (MRI) scans were acquired on a 3T Philips scanner. VBM data were processed using Statistical Parametric Mapping (SPM) software in MATLAB the MNI coordinate system. We performed exploratory voxel-wise comparisons of GMVs among the three groups using an analysis of covariance (ANCOVA) model in SPM. Results were considered significant if they retained significance after family-wise error (FWE) correction for multiple comparisons (p<0.05). All the analyses were adjusted for age, sex, education in years, and total brain GMV.

The whole-brain exploratory analyses revealed no significant findings at the p<0.05 level (FWE-corrected). However, pairwise comparisons revealed significant changes betweeen FEP patients and their unaffected siblings. In particular, FEP patients had decreased volumes in the right side of the following regions (FEW = 0.047): superior temporal cortex, Rolandic operculum, insula, Heschel’s gyrus, supramarginal gyrus, superior temporal pole, hippocampus, parahippocampal gyrus, fusiform gyrus, amydgala, olfactory, inferior frontal operculum, cerebellum, posterior and medial orbital frontal cortex, rectus, medial temporal, medial frontal, and putamen. FEP patients also showed decreased volumes on the left side of the following regions (FWE 0.049): frontal superior medial gyrus, superior frontal gyrus, frontal middle part, caudate, anterior cingulate cortex, thalamus, and pallidum. Patients also showed widespread reduced GMV in various GMVs regions compared to controls at FWE<0.05. However, no difference was found between siblings and controls (FWE: >0.05).

The study of healthy siblings of patients with heritable illnesses could help in the understanding of the contribution of genetic background and environmental factors to illness state and predisposition. Differences between patients and their siblings could be attributed to the disease state, considering that the unaffected sibling group and unrelated healthy control group did not differ. We will next evaluate biological and environmental contributors to the reported differences.

None Declared

Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample.

Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of ‘Genetic’ models (solely fitted with PRS-SZ), ‘Environmental’ models (solely fitted with each environmental stressor), ‘Independent’ models (with PRS-SZ and each environmental factor), and ‘Interaction’ models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models.

There were no genes-environment associations. PRS-SZ was associated with positive dimensions (β = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension.

This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.

We have previously shown that the association between frequent cannabis use and psychosis is more likely in subgroups with low-grade inflammation than subgroups without (PMID: 33736715). The role of immune-related polymorphisms remains unknown.

To explore whether polymorphisms affecting the function of key immune regulatory proteins moderate the association between cannabis and psychosis, namely: ENTPD1 and NT5E, involved in the synthesis of CD39, CD73, respectively, and anti-inflammatory adenosine; CTLA4 and FOXP1, essential for Treg functional capacity.

We genotyped blood samples from 283 community-based controls and 140 recent-onset psychosis patients in Brazil (EU-GEI consortium, Ribeirão Preto/SP) for twelve polymorphisms (ENTPD1: rs3814159, rs3176891, rs10748643; NT5E: rs9444348, rs2295890; CTLA4: rs3087243, rs231775, rs5742909, rs4553808; FOXP1: rs6803008, rs6786408, rs830599; Illumina Human Core Exome-24). Cannabis frequency (daily, less than daily, never) was assessed by self-report (Cannabis Experience Questionnaire). Binary logistic regression models (OR,95%CI) included case status as the outcome, genotype (dominant model), cannabis frequency, and an interaction term between the two as exposure, adjusting for confounders (age, sex, ethnicity, tobacco smoking).

We found significant interactions between cannabis use and polymorphisms for ENTPD1 (rs3814159), NT5E (rs9444348), and FOXP1 (rs6786408). Less than daily or daily use were, in a dose-response fashion, only associated with psychosis in those with the variant and heterozygous genotypes; less than daily: ENTPD1 AG/GG (3.34,1.71-6.50); NT5E AG/AA (3.71,1.87-7.33); FOXP1 AC/CC (2.98,1.54-5.77); daily: ENTPD1 AG/GG (16.81;5.89-47.96); NT5E AG/AA (21.20,6.81-66.01); FOXP1 AC/CC (13.75,5.22-36.21).

Variation in genes that affect Treg function appears to modify the effect of cannabis consumption on psychosis in keeping with Treg hypofunction hypothesis (PMID:33713699).

No significant relationships.

We assessed self-reported drives for alcohol use and their impact on clinical features of alcohol use disorder (AUD) patients. Our prediction was that, in contrast to “affectively” (reward or fear) driven drinking, “habitual” drinking would be associated with worse clinical features in relation to alcohol use and higher occurrence of associated psychiatric symptoms.

Fifty-eight Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol abuse patients were assessed with a comprehensive battery of reward- and fear-based behavioral tendencies. An 18-item self-report instrument (the Habit, Reward and Fear Scale; HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) motivations for alcohol use. To characterize clinical and demographic measures associated with habit, reward, and fear, we conducted a partial least squares analysis.

Habitual alcohol use was significantly associated with the severity of alcohol dependence reflected across a range of domains and with lower number of detoxifications across multiple settings. In contrast, reward-driven alcohol use was associated with a single domain of alcohol dependence, reward-related behavioral tendencies, and lower number of detoxifications.

These results seem to be consistent with a shift from goal-directed to habit-driven alcohol use with severity and progression of addiction, complementing preclinical work and informing biological models of addiction. Both reward-related and habit-driven alcohol use were associated with lower number of detoxifications, perhaps stemming from more benign course for the reward-related and lack of treatment engagement for the habit-related alcohol abuse group. Future work should further explore the role of habit in this and other addictive disorders, and in obsessive-compulsive related disorders.

Latin America Treatment and Innovation Network in Mental Health (LATIN-MH) is a research hub located in Brazil and Peru that conducts a research project to help reduce the treatment gap in mental health in Latin America (LA). Besides its research core, LATIN-MH has a Capacity Building (CB) component that aims to help young researchers receive the specific training to contribute to the growing scientific production in mental health in LA.

LATIN-MH proposal in CB includes a series of actions to prepare professionals in the research area. The main proposals are described here, which include online study groups, promotion of scientific meetings, hands-on training in different levels and sharing of information.

LATIN-MH CB activities are at its initial stages but the proposed activities were well evaluated by the participants. The first participating fellows who finished their fellowships are contributing elsewhere in the mental treatment and human resources formation area.

The repercussion of LATIN-MH actions in CB and its evaluation, particularly on the formation of human resources and dissemination of information, show that the hub is contributing to the critic formation of young researchers and the circulation of important information.

Despite the extensive literature assessing associations between religiosity/spirituality and health, few studies have investigated the clinical applicability of this evidence. The purpose of this paper was to assess the impact of religious/spiritual interventions (RSI) through randomized clinical trials (RCTs).

A systematic review was performed in the following databases: PubMed, Scopus, Web of Science, PsycINFO, Cochrane Collaboration, Embase and SciELO. Through the use of a Boolean expression, articles were included if they: (i) investigated mental health outcomes; (ii) had a design consistent with RCTs. We excluded protocols involving intercessory prayer or distance healing. The study was conducted in two phases by reading: (1) title and abstracts; (2) full papers and assessing their methodological quality. Then, a meta-analysis was carried out.

Through this method, 4751 papers were obtained, of which 23 remained included. The meta-analysis showed significant effects of RSI on anxiety general symptoms (p < 0.001) and in subgroups: meditation (p < 0.001); psychotherapy (p = 0.02); 1 month of follow-up (p < 0.001); and comparison groups with interventions (p < 0.001). Two significant differences were found in depressive symptoms: between 1 and 6 months and comparison groups with interventions (p = 0.05). In general, studies have shown that RSI decreased stress, alcoholism and depression.

RCTs on RSI showed additional benefits including reduction of clinical symptoms (mainly anxiety). The diversity of protocols and outcomes associated with a lack of standardization of interventions point to the need for further studies evaluating the use of religiosity/spirituality as a complementary treatment in health care.

Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use.

Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated.

No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum.

Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

To investigate the predictors of change in physical activity (PA) from early to mid adolescence in a cohort of adolescents.

Prospective, population-based birth cohort study. PA level was evaluated by means of questionnaire, and was analysed in continuous form (min/week) and as a trajectory (inactive–inactive, inactive–active, active–inactive, active–active) based on the cut-off point of 300 min/week.

Pelotas, a city of 340 000 inhabitants in southern Brazil.

Adolescents (n 4120) followed from 11 to 15 years of age.

Maternal PA change and more exposure to outdoors were directly associated with a positive change in PA level (min/week) for both genders. Higher maturation status (among boys) and later menarche were also associated with positive PA change in min/week. Predictors to remain inactive were: maternal PA change (inverse association), more exposure to outdoors, higher socio-economic level, fear of living in the neighbourhood and non-overweight girls. Predictors to become inactive were higher socio-economic level among boys and increase in screen time among girls.

The study demonstrates that social, family, biological, behavioural and environmental factors exert an important role in the PA change among youngsters as they move into adolescence. These findings may be relevant to the design of policies and intervention programmes aimed at promoting PA in teenagers.

Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP).

FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination.

We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction.

Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.

Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes.

Longitudinal regional grey matter volume and ventricle:brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study.

While there was no longitudinal difference in ventricle:brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits.

Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.

A consistent association between paternal age and their offspring's risk of schizophrenia has been observed, with no independent association with maternal age. The relationship of paternal and maternal ages with risk of bipolar affective disorders (BPAD) in the offspring is less clear. The present study aimed at testing the hypothesis that paternal age is associated with their offspring's risk of BPAD, whereas maternal age is not.

This population-based cohort study was conducted with individuals born in Sweden during 1973–1980 and still resident there at age 16 years. Outcome was first hospital admission with a diagnosis of BPAD. Hazard ratios (HRs) were calculated using Cox's proportional hazard regression.

After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (CI) 1.11–1.48], but this fell to 1.20 (95% CI 0.97–1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08–1.56) before adjustment for paternal age, HR 1.12 (95% CI 0.86–1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01–1.57) and it was 1.45 (95% CI 1.16–1.81) if both parents were >30 years.

Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.