Possible Interaction of Environmental and Biological Factors in the Etiology of Schizophrenia: Review and Integration

Strahilevitz, Meir

doi:10.1177/070674377401900218

Cited by 6 publications

(2 citation statements)

References 86 publications

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“…Both environmental and genetic factors are associated with an increased risk of developing psychotic disorders (van Os et al ., 2010 ). The relationships between these factors have long been discussed, and the hypothesis of genes x environment (GxE) interactions was suggested several decades ago (Strahilevitz, 1974 ; Murray et al ., 1986 ; Schulsinger et al ., 1987 ). Such interaction can be defined as a genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression (Kendler and Eaves, 1986 ).…”

Section: Introductionmentioning

confidence: 99%

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

Pignon

Peyre

Ayrolles

et al. 2022

Epidemiol Psychiatr Sci

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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.

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Section: Introductionmentioning

confidence: 99%

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

Pignon

Peyre

Ayrolles

et al. 2022

Epidemiol Psychiatr Sci

View full text Add to dashboard Cite

show abstract

“…Both environmental and genetic factors are associated with an increased risk of developing psychotic disorders (van Os et al, 2010). The relationships between these factors have long been discussed, and the hypothesis of genes x environment (GxE) interactions was suggested several decades ago (Strahilevitz, 1974;Murray et al, 1986;Schulsinger et al, 1987). Such interaction can be defined as a genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression (Kendler and Eaves, 1986).…”

Section: Introductionmentioning

confidence: 99%

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

Pignon

Peyre

Ayrolles³

et al. 2022

Preprint

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Gene x environment (GxE) interactions have not been reliably established regarding etiology of psychotic disorders, while genes-environment (G-E) associations have been displayed. 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 polygenic risk scores for schizophrenia (PRS-SZ) on subclinical psychosis in a population-based sample. Data were drawn from the 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. For each dimension, the interactions between genes and environment were assessed 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 (with an interaction term between the PRS-SZ and each environmental factor). There were no direct G-E associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except for low 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 healthy individuals suggests that i) the etiological 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.

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d-Amphetamine and punished responding: The role of catecholamines and anorexia

Lazareno

1979

Psychopharmacology

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Rats were trained to press a lever for food on a schedule in which components of variable interval reinforcement (V12') alternated with conflict components in which every response resulted in food delivery and footshock. Low doses of d-amphetamine selectively suppressed responding in the conflict component in a dose-dependent manner, whereas prefeeding suppressed responding in both components. Pretreatment with noradrenergic blocking agents (propranolol, phentolamine and phenoxybenzamine) did not diminish the suppressant effect of d-amphetamine, but this effect was reduced by pretreatment with alpha-methyl-para-tyrosine methylester and dopamine blockers (spiroperidol, haloperidol and clozapine) indicating that d-amphetamine was exerting its selective suppressant effect via the release of dopamine. It is suggested that the effects of low doses d-amphetamine on behaviour in conflict situations may provide a useful model for investigating the mode of action of neuroleptic drugs.

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Possible Interaction of Environmental and Biological Factors in the Etiology of Schizophrenia: Review and Integration

Cited by 6 publications

References 86 publications

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

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

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

d-Amphetamine and punished responding: The role of catecholamines and anorexia

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