European Network Of National Schizophrenia Networks Studying Gene-Environment Interactions Research Articles

Post-migration trajectories and psychopathological vulnerability

Abstract: BackgroundPsychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.MethodsWe used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case-control study. We defined a set of 3 indicators of social disadvantage for each phase: pre-migration, migration, and post-migration.Results249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95%CI 1.06-2.44, p=0.027) and postmigration social disadvantages (OR 1.89, 95%CI 1.02-3.51, p=0.044), along with expectations/achievements mismatch (OR 1.14, 95%CI 1.03-1.26, p=0.014) were all significantly associated with psychosis. We found a dose-response effect between number of adversities across all phases and odds of psychosis (≥6: OR 14.09, 95%CI 2.06-96-47, p=0.007).ConclusionsThe cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may be reduce the excess of psychosis in migrants.Disclosure of InterestNone Declared

Environmental Factors in the Etiology of Mental Disorders in the Czech Republic.

Both genetic and environmental factors are important in etiology of mental disorders. Calculating polyenviromic risk/protective scores provides an updated perspective in research on the environmental causes of psychiatric disorders. We aimed to compare environmental risk and protective factors in patients with psychosis or a mood disorder (PSYCH+MOOD) and those with an anxiety disorder (ANX). We administered the internationally accepted questionnaire from the EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study, enriched with mood and anxiety disorder-relevant measures, to patients at two large university hospitals in the Czech Republic. Ninety-four PSYCH+MOOD patients (average age 42.5 years; 46 males) and 52 ANX patients (average age 47.2 years; 17 males) participated. Neither polyenviromic risk score nor polyenviromic protective score differed significantly between PSYCH+MOOD and ANX groups (p = 0.149; p = 0.466, respectively). Scientific validity of the polyenviromic risk/protective score construct must still be demonstrated in large psychiatric samples, ideally in prospective studies. Nevertheless, researchers have already started to investigate environmental factors in the etiology of mental disorders in their complexity, similarly to polygenic risk scores.

Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study.

Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54-0.92] and PRS-D (OR = 1.31, 95% CI 1.06-1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23-3.74). Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study.

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.

Association between tobacco use and symptomatology in individuals at ultra-high risk to develop a psychosis: A longitudinal study

BackgroundThe high prevalence rates and impact of tobacco smoking in individuals with a psychotic disorder have become an increasing interest. Little is known about tobacco smoking in individuals at ultra-high risk of psychosis (UHR). MethodsWe studied 345 UHR individuals of the high-risk study of the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI). Smoking status and the number of cigarettes per day were assessed at multiple moments using the CIDI. Symptom severity at each time point was assessed using CAARMS. Linear mixed-effects analyses were conducted to examine the multi-cross-sectional and prospective associations between (change in) smoking behaviour and symptomatology. FindingsAt baseline, 175 individuals (53%) smoked tobacco with an average of 12.4 (SD = 9.0) cigarettes per day. Smokers did not significantly differ in symptom severity from non-smokers on general, positive, negative, emotional, cognitive, behavioural, or motor symptoms across time. However, associations were found between the number of cigarettes and the severity of general psychopathology (estimate 0.349, SE 0.146, p = 0.017). Change in the number of cigarettes had no significant effect on change in general symptom severity (estimate 0.330, SE 0.285, p = 0.248). InterpretationSmoking prevalence in UHR individuals is high. Cigarette consumption was associated with higher levels of general symptoms. However, we observed no association between change in number of cigarettes and symptom severity. Given the fact that smoking is associated with poorer health and worse outcomes in people with psychosis, the clinical high-risk phase offers a window of opportunity for prevention and cessation interventions.

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0–38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8–30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.

Migration history and risk of psychosis: results from the multinational EU-GEI study.

Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration. We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case-control study. We defined a set of three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models. In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06-2.44, p = 0.027) and post-migration social disadvantages (OR 1.89, 95% CI 1.02-3.51, p = 0.044), along with expectations/achievements mismatch (OR 1.14, 95% CI 1.03-1.26, p = 0.014) were all significantly associated with psychosis. Migration adversities (OR 1.18, 95% CI 0.672-2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose-response effect between the number of adversities across all phases and odds of psychosis (⩾6: OR 14.09, 95% CI 2.06-96.47, p = 0.007). The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may reduce the excess of psychosis in migrants.

Impact of smoking Behavior on cognitive functioning in persons at risk for psychosis and healthy controls: A longitudinal study.

The high prevalence of smoking in individuals who are at ultra-high risk (UHR) for psychosis is well known and moderate cognitive deficits have also been found in UHR. However, the association between smoking and cognition in UHR is unknown and longitudinal studies are lacking. A cohort study with 330 UHR individuals and 66 controls was conducted, as part of the European network of national schizophrenia networks studying gene-environment interactions (EU-GEI). At baseline and after 6, 12, and 24months, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a comprehensive test battery. Linear mixed-effects analyses were used to examine the multicross-sectional and prospective associations between (change in) smoking behavior and cognitive functioning, accounting for confounding variables. At baseline, 53% of UHR and 27% of controls smoked tobacco. Smoking UHR and controls did not significantly differ from nonsmoking counterparts on the tested cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, or reasoning/problem solving) across different assessment times. Neither smoking cessation nor initiation was associated with a significant change in cognitive functioning in UHR. No associations were found between smoking and cognitive impairment in UHR nor in controls. However, the fact that one in every two UHR individuals report daily use of tobacco is alarming. Our data suggest that UHR have fewer cognitive impairments and higher smoking cessation rates compared to patients with first-episode psychosis found in literature. Implications to promote smoking cessation in the UHR stage need further investigation.

The incidence of psychotic disorders among migrants and minority ethnic groups in Europe: findings from the multinational EU-GEI study.

In Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: 'minorities'). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population). The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of Diseases, 10th edition, codes F20-F33) from 13 sites. The standardized incidence rates for minorities, combined into one category, varied from 12.2 in Valencia to 82.5 per 100 000 in Paris. These rates were generally high at sites with high rates for the reference population, and low at sites with low rates for the reference population. IRRs for minorities (combined into one category) varied from 0.70 (95% CI 0.32-1.53) in Valencia to 2.47 (95% CI 1.66-3.69) in Paris (test for interaction: p = 0.031). At most sites, IRRs were higher for persons from non-Western countries than for those from Western countries, with the highest IRRs for individuals from sub-Saharan Africa (adjusted IRR = 3.23, 95% CI 2.66-3.93). Incidence rates vary by region of origin, region of destination and their combination. This suggests that they are strongly influenced by the social context.

Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence

Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020. In EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma samples in EU-GEI and plasma samples at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models. The EU-GEI subsample (133 participants at CHR (mean [SD] age, 22.6 [4.5] years; 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95; positive predictive value [PPV], 75.0%; and negative predictive value [NPV], 98.6%). Functional analysis of differentially expressed proteins implicated the complement and coagulation cascade. A model based on the 10 most predictive proteins accurately predicted transition status in training (AUC, 0.99; PPV, 76.9%; and NPV, 100%) and test (AUC, 0.92; PPV, 81.8%; and NPV, 96.8%) data. The ALSPAC subsample (121 participants from the general population with plasma samples available at age 12 years (61 [50.4%] male) comprised 55 participants (45.5%) with PEs at age 18 years and 61 (50.4%) without PEs at age 18 years. A model using proteomic data at age 12 years predicted PEs at age 18 years, with an AUC of 0.74 (PPV, 67.8%; and NPV, 75.8%). In individuals at risk of psychosis, proteomic biomarkers may contribute to individualized prognosis and stratification strategies. These findings implicate early dysregulation of the complement and coagulation cascade in the development of psychosis outcomes.

S95. DIFFERENCES IN LIFETIME PATTERNS OF PSYCHOSTIMULANTS AND THEIR IMPACT ON THE PROPORTION OF PATIENTS WITH FIRST-EPISODE PSYCHOSIS ATTRIBUTABLE TO PSYCHOSTIMULANTS USE ACROSS EUROPE

BackgroundSubstance use may be a risk factor for the onset of schizophrenia. Almost 50 % of people with first episode psychosis (FEP) have a history of cannabis or alcohol use. Smaller but significant proportions of this population have a history of psychostimulants (PS) use. Cross-sectional studies have shown a link between recreational and regular use of PS and psychotic symptoms, particularly among individuals with PS dependence, that usually revert after drug withdrawal. Nevertheless, some PS users suffer not just spontaneous relapse of the symptoms but also persistent psychosis in the absence of the drug.European data are not available for a large sample of the prevalence of consumption and its relation to the severity of symptoms in FEP. For this purpose, we described the differences in patterns of use of PS current and lifetime between FEP and healthy controls (HC) and their impact on the severity of the clinical symptomatology.MethodsThis analysis is based on data from the case-control study work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI), which took part between 2010 and 2015 across six countries.901 FEP patients (M age=30.76, SD= 10.51; 38.1% females) and 1235 HC (M=36.15, SD=13.30; 53% females) were included in the present case-control study. Data related to amphetamine use were obtained through CEQEU-GEI. To assess psychopathology the OPerational CRITeria (OPCRIT) system was used.Group comparisons were made using t-test or Chi square, and ANCOVA or logistic regression controlling for age, sex and cannabis use when appropriate.ResultsFEP subjects displayed a trend for higher use of PS in the last year (B=-0.18, p= 0.055: 81 (9%) FEP and 56 (4.5%)) and a significant higher lifetime use (Chi2= 37.33, p<0.001: 196 (21.8%) FEP and 149 (12.1%) HC) than HC, but the frequency of PS use did not differ between groups.Lifetime FEP PS-users showed higher scores, thus is, more severe symptoms in the Mania (t= -3.69, p< 0.001) and the general (t= -3.47, p= 0.001) factors compared to FEP non-PS-users. Current FEP PS-users showed higher scores in the Mania factor (t= -2.52, p= 0.012) than FEP non-PS-users. However, these results were not significant when the comparisons were adjusted for age, sex and cannabis use. FEP PS-users displayed lower scores than the non-users in the negative factor both in the last year (t= 2.10, p= 0.038 and: F1,866= 4.27, p= 0.039 when adjusted for age, sex and cannabis use) and lifetime (t= 1.99, p= 0.046 and F1,869= 1.37, p= 0.243 when adjusted for age, sex and cannabis use).DiscussionAs previous studies, we confirmed the higher rates of PS use in FEP than HC in a European study with a big sample. PS use was related to severity of clinical symptomatology. PS-users presented more severe general symptoms and, specifically, in the mania factor. Otherwise, FEP non-PS-user showed higher scores in the negative factor which might be related to the usual course of the psychosis without exposure to PS use.

S126. THE RELATION OF THE PSYCHOSIS CONTINUUM WITH SCHIZOPHRENIA POLYGENIC RISK SCORE AND CANNABIS USE

BackgroundThere has been much debate about whether research into psychosis should be conducted using symptom dimensions as opposed to diagnostic categories. Indeed, dimensions, like categories, may be practical but arbitrary tools for research and clinical practice; hence, they should not be based on psychometric data only. The aim of this study was to externally validate empirically derived symptom dimensions using combined genetic and environmental data. Specifically, we examined the hypothesis that the continuous multivariate distribution of psychosis is a function of cannabis use and genetic liability to schizophrenia, as summarised by polygenic risk score (SZ-PRS).MethodsAs part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study, we analysed a large multinational sample of First Episode Psychosis patients (FEP) and population controls, with available genotype and psychopathology information. Using item response modelling in Mplus, we estimated a bifactor model of psychotic symptoms in FEP, and of psychotic experiences in controls. Using PRSice, we built SZ-PRS by weighting individuals’ risk variants by the log(odds ratio), where the odds ratio was extracted from the latest summary statistics of Psychiatric Genomic Consortium mega-analyses on schizophrenia. Finally, we used linear regression to test the combined associations of the positive symptom/experience dimensions with SZ-PRS and daily/current cannabis use, separately in FEP and controls, after covarying for 10 ancestry principal components, sex, age, and primary diagnosis.ResultsThe continuous distribution of psychosis was represented by two bi-factor models composed of 1) in FEP, one general psychosis factor and five specific dimensions; 2) in controls, one general psychosis factor and three specific dimensions.Linear regression modelling showed that in 617 FEP, both daily cannabis use (B=0.31; 95%CI 0.11 to 0.52; p=0.002) and SZ-PRS (B=0.22; 95%CI 0.04 to 0.39; p=0.014) were independently associated with the dimension of positive symptoms. Similar results were found in 979 population controls, with a positive association of both current use of cannabis (B=0.26, 95%CI 0.06 to 0.46; p=0.011) and SZ-PRS (B=0.13, 95%CI 0.02 to 0.25; p=0.022) with the dimension of psychotic experiences.DiscussionWe found two factors associated with the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions of positive symptoms, contributing to variation across the psychosis continuum. Our study supports the theory that psychotic experiences in the general population are biologically similar to clinical psychotic symptoms.

Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case-control study.

Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.

Social disadvantage, linguistic distance, ethnic minority status and first-episode psychosis: results from the EU-GEI case–control study

Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns. We used case-control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20-F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data. Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69-2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31-1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22-1.89) and linguistic distance (OR 1.22, 95% CI 0.95-1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively. Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.

Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis

The development of adverse clinical outcomes in patients with psychosis has been associated with behavioral and neuroanatomical deficits related to emotion processing. However, the association between alterations in brain regions subserving emotion processing and clinical outcomes remains unclear. To examine the association between alterations in emotion processing and regional gray matter volumes in individuals at clinical high risk (CHR) for psychosis, and the association with subsequent clinical outcomes. This naturalistic case-control study with clinical follow-up at 12 months was conducted from July 1, 2010, to August 31, 2016, and collected data from 9 psychosis early detection centers (Amsterdam, Basel, Cologne, Copenhagen, London, Melbourne, Paris, The Hague, and Vienna). Participants (213 individuals at CHR and 52 healthy controls) were enrolled in the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) project. Data were analyzed from October 1, 2018, to April 24, 2019. Emotion recognition was assessed with the Degraded Facial Affect Recognition Task. Three-Tesla magnetic resonance imaging scans were acquired from all participants, and gray matter volume was measured in regions of interest (medial prefrontal cortex, amygdala, hippocampus, and insula). Clinical outcomes at 12 months were evaluated for transition to psychosis using the Comprehensive Assessment of At-Risk Mental States criteria, and the level of overall functioning was measured through the Global Assessment of Functioning [GAF] scale. A total of 213 individuals at CHR (105 women [49.3%]; mean [SD] age, 22.9 [4.7] years) and 52 healthy controls (25 women [48.1%]; mean [SD] age, 23.3 [4.0] years) were included in the study at baseline. At the follow-up within 2 years of baseline, 44 individuals at CHR (20.7%) had developed psychosis and 169 (79.3%) had not. Of the individuals at CHR reinterviewed with the GAF, 39 (30.0%) showed good overall functioning (GAF score, ≥65), whereas 91 (70.0%) had poor overall functioning (GAF score, <65). Within the CHR sample, better anger recognition at baseline was associated with worse functional outcome (odds ratio [OR], 0.88; 95% CI, 0.78-0.99; P = .03). In individuals at CHR with a good functional outcome, positive associations were found between anger recognition and hippocampal volume (ze = 3.91; familywise error [FWE] P = .02) and between fear recognition and medial prefrontal cortex volume (z = 3.60; FWE P = .02), compared with participants with a poor outcome. The onset of psychosis was not associated with baseline emotion recognition performance (neutral OR, 0.93; 95% CI, 0.79-1.09; P = .37; happy OR, 1.03; 95% CI, 0.84-1.25; P = .81; fear OR, 0.98; 95% CI, 0.85-1.13; P = .77; anger OR, 1.00; 95% CI, 0.89-1.12; P = .96). No difference was observed in the association between performance and regional gray matter volumes in individuals at CHR who developed or did not develop psychosis (FWE P < .05). In this study, poor functional outcome in individuals at CHR was found to be associated with baseline abnormalities in recognizing negative emotion. This finding has potential implications for the stratification of individuals at CHR and suggests that interventions that target socioemotional processing may improve functional outcomes.

Psychiatric Genetics In Eastern Europe: Progress And Challenges

The psychiatric genetics is rapidly growing through new technological developments and collaborations among research groups worldwide. Unfortunately, Eastern Europe is still in need for more organized genetic research in psychiatry. Particularly, education of psychiatrists in genetics is warranted, as well as multidisciplinary approach among different scientific fields should be implemented in an advanced approach. There are several progresses that have been made due to psychiatric genetic networks such as Psychiatric Genomics Consortium (PGC) and European network of national schizophrenia networks studying gene-environment interactions (EU-GEI). I will present progress regarding genetics networks that have been already established as well as the advantages of future collaborations. In addition, I will discuss certain challenges that we are facing today in Eastern Europe for a better genetics implementation in psychiatric field.

5.4 BIOLOGICAL AND EPIDEMIOLOGICAL EXAMINATION OF TRANSDIAGNOSTIC AND SPECIFIC SYMPTOM DIMENSIONS AT PSYCHOSIS ONSET: FINDINGS FROM THE EUGEI STUDY

BackgroundCurrent diagnostic models of psychosis have been questioned since Kraepelin’s original dichotomy of dementia praecox and manic depression. Indeed, increasing evidence has suggested that a dimensional approach might be a valid alternative platform for research. However, while an increasing number of studies have investigated how environmental risk factors for affective and non-affective psychosis map onto symptom dimensions, only a few have examined these dimensions in relation to genetic variants as summarised by Polygenic Risk Score (PRS). Furthermore, no studies have examined the putative effect of PRS for Schizophrenia (SZ), Bipolar Disorder (BP), and Major Depressive Disorder (MDD) on previously identified general and specific symptom dimensions. At the same time, only one study has investigated how symptoms vary according to epidemiological factors such as living in urban neighbourhoods. The objectives of this study were to: 1) test whether a bi-factor model statistically fits the conceptualization of psychosis as composed of general and specific dimensions; 2) examine the extent to which SZ, BP, and MDD PRSs explain the phenotypic variance due to general and specific dimensions; 3) test the hypothesis that the general psychosis dimension would be more severe in highly urban environments.MethodsWe used clinical and epidemiological data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EUGEI) study, including 2322 First Episode Psychosis (FEP) patients recruited in 17 sites across 6 countries. Genetic variants were collectively analyzed for 800 individuals.The following analysis steps were performed:1) Psychopathology items were analysed using multidimensional item response modelling in MPlus to estimate unidimensional, multidimensional, and bi-factor models of psychosis. Model fit statistics included Log-Likelihood, and Akaike and Bayesian Information Criteria to compare these models.2) SZ, BP, and MDD PRSs for general and specific dimensions were built using PRSice. Summary statistics from large case-control mega-analyses from the Psychiatric Genomics Consortium were used as base data sets and general and specific dimension scores were used as discovery data sets. Individuals’ number of risk alleles in the discovery sample was weighted by the log odds ratio from the base samples, accounting for population stratification, and summed into the three PRSs.3) Multilevel regression analysis was used in STATA 14 to examine the variance in general dimension due to the population density levels across the sites.ResultsA bi-factor solution, composed of one general and five specific symptom dimensions, showed the best model fit statistics.Higher SZ PRS score was associated with higher scores on positive dimensions (β= 0.27, t=2.11, p<0.05); higher BP PRS was associated with higher scores on mania dimension (β= 0.17, t=2.11, p<0.05); higher MDD PRS was associated with lower scores on negative dimension (β= -0.31, t=-2.25, p<0.05). No trends of association were found for SZ, BP, or MDD PRSs and the general psychosis dimension.The transdiagnostic symptom dimension score was elevated in people living in more densely populated sites (η2=0.077, 95% CI 0.057–0.098).DiscussionOur results suggest that a) symptom dimension structure at FEP is best represented by the bi-factor model; b) in FEP patients, there is a trend of associations between SZ PRS and positive dimension, and between BP PRS and mania dimension; and c) elevated level of transdiagnostic symptomatology was observed in more densely populated sites.

Child Maltreatment and Clinical Outcome in Individuals at Ultra-High Risk for Psychosis in the EU-GEI High Risk Study.

Child maltreatment has been associated with a wide range of mental disorders in adulthood. Whether child maltreatment is specifically associated with psychosis risk in individuals at ultra-high risk (UHR) for psychosis, or leads to a general vulnerability for overall psychopathology in the UHR stage remains unclear. The present study examines the association between child maltreatment and transition to psychosis and other mental disorders. The sample consisted of 259 UHR individuals from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Participants were followed-up for 2 years to assess clinical outcome. Clinical outcome was assessed at 6 months, 12 months, and 24 months after baseline. Child maltreatment before the age of 17 years was assessed at baseline. Our findings show that a history of emotional abuse was associated with an increased risk for transition to psychosis (OR = 3.78, 95% CI = 1.17 to 12.39, P = .027). Apart from psychosis, a history of physical abuse was associated with depressive disorder (OR = 4.92, 95% CI = 2.12 to 11.39, P = .001), post-traumatic stress disorder (OR = 2.06, 95% CI = 1.10 to 3.86, P = .023), panic disorder (OR = 2.00, 95% CI = 1.00 to 3.99, P = .048) and social phobia (OR = 2.47, 95% CI = 1.18 to 5.16, P = .016) at follow-up. Our findings suggest that in the UHR stage child maltreatment is a pluripotent risk factor for developing psychosis, depressive disorder, post-traumatic stress disorder (PTSD), panic disorder, and social phobia in adulthood.

Trauma and migration in first episode psychosis

IntroductionResearches show that the period of migration, or the migration process itself, may confer an increased risk for psychosis. Some studies have addressed whether the high rates of psychosis found in migrants could be due to higher genetic or environmental risk factors. Facing severe or chronic stress such as trauma, social isolation, low socio-economic status, late-life social adversity may result in long term, sometimes permanent, alterations of the biological stress response system, leading to the onset of psychosis.ObjectivesThis study aims to examine, in a large sample of first episode psychosis patients, whether negative social experiences like stressful life events and difficulties, trauma and isolation have significantly higher frequencies in migrants with respect to natives.MethodsThe present study is conducted within the framework of the EUGEI (European Network of National Schizophrenia Networks Studying Gene Environment Interactions) study, a Europe-wide incidence and case–control study of psychosis conducted in 12 centers chosen to include areas with large first and subsequent generation migrant populations.Data about age, gender, migration history, trauma, life events, ethnicity, social class and family history of mental disorders have been collected.ResultsPreliminary data on the relationship between trauma and migration in first episode psychosis will be presented.ConclusionsSince migration is an important stressful life event, and difficulties in integration in host countries may remain chronic, it is important to identify in each context the most vulnerable minority groups in order to implement targeted prevention interventions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Risks Factors for Psychosis in Migrants: Preliminary Results From the Eugei and Pep-ita Study in Italy

Research mostly conducted inthe UK and Northern Europe has established that there are high rates of firstepisode psychosis (FEP) in large cities and immigrant populations. Thesefindings could indicate that socio-environmental risk factors, such asindividual social class and social capital; early trauma, life events; cannabisuse and neighbourhood deprivation could be relevant in explaining thedifferences in incidence rates observed between migrants and natives, followingthe socio-developmental model of Morgan et al (2010). Further studies, with population based control groups for comparison, such as the recentlystarted pan-European EUGEI (European Network of NationalSchizophrenia Networks Studying Gene Environment Interactions) and PEP-Itastudy (first episode psychosis in Italy study) will allow a deeperunderstanding of the nature of FEP incidence rate found among FEP natives and FEPmigrants. This presentation aims to compare the incidence rate of FEP andthe distribution of several risk factors (e.g. substance abuse, neighbourhooddeprivation, urbanicity and trauma) in migrants in different places in acrossItaly. Tarricone I, Braca M 1 , Allegri F, et al (2014) First-episode psychosi and migration in Italy(PEP-ITA migration): a study in the Italian mental health services. BMC Psychiatry. 14:186.