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

Abstract

Aims 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. Methods 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. Results 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. Conclusions 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.

Psychosocial stress, interpersonal sensitivity, and social withdrawal in clinical high risk for psychosis: a systematic review

“…Environmental risks have also been found to act additively and synergistically with childhood trauma [87][88][89] and stressful life events 90,91 , contributing to the persistence of subthreshold psychosis symptoms in the general population. Psychosocial stressors such as childhood trauma and stressful life events have further been associated with higher levels of positive, negative, and depressive symptoms in the general population 92,93 . In addition, these psychosocial stressors, along with polygenic risk 65 Yes Yes Yes Hogdes et al 118 Yes n/a n/a Jang et al 131 Yes n/a n/a Mason et al 135 Yes n/a Yes Shim et al 125 Yes No n/a Wiesman van der Teen et al 64 No Yes n/a scores were found to exhibit independent additive effects on these three dimensions of subclinical psychosis 92,93 further supporting the stress-vulnerability hypothesis.…”

“…Psychosocial stressors such as childhood trauma and stressful life events have further been associated with higher levels of positive, negative, and depressive symptoms in the general population 92,93 . In addition, these psychosocial stressors, along with polygenic risk 65 Yes Yes Yes Hogdes et al 118 Yes n/a n/a Jang et al 131 Yes n/a n/a Mason et al 135 Yes n/a Yes Shim et al 125 Yes No n/a Wiesman van der Teen et al 64 No Yes n/a scores were found to exhibit independent additive effects on these three dimensions of subclinical psychosis 92,93 further supporting the stress-vulnerability hypothesis. However, it is important to note that no gene-environment interaction was found 93 .…”

“…In addition, these psychosocial stressors, along with polygenic risk 65 Yes Yes Yes Hogdes et al 118 Yes n/a n/a Jang et al 131 Yes n/a n/a Mason et al 135 Yes n/a Yes Shim et al 125 Yes No n/a Wiesman van der Teen et al 64 No Yes n/a scores were found to exhibit independent additive effects on these three dimensions of subclinical psychosis 92,93 further supporting the stress-vulnerability hypothesis. However, it is important to note that no gene-environment interaction was found 93 . These general population studies appear to parallel the CHR findings 22 and are consistent with the stress-vulnerability and stress sensitivity models, whereby the cumulative effects of stress increase the likelihood of psychosis expression and increased affective arousal in response to such stressors, respectively.…”

Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors

“…However, current evidence suggest that G × E might not be the only process relevant for SZ risk. Other models like GE correlation (Warrier et al 2021), or even pure additive models with no interaction (Pignon et al 2022) might also drive the effects of childhood trauma or other sources of psychosocial stress on SZ risk.…”

The risk of hospitalization for psychotic disorders following hospitalization for COVID-19: a French nationwide longitudinal study

“…It is possible that such an abnormal response can occur after SARS-COV-2 infection, increasing the risk of rst-episode psychosis (FEP) [9]. Moreover, SARS-COV-2 infection -especially severe forms -represents a stressor and a negative life event, and could cause or trigger a psychotic disorder [10][11][12].…”