Interazioni geni-ambiente nella schizofrenia

Background: Family, twin, and adoption studies have firmly established the roles of both genes and environment in schizophrenia, suggesting how gene-environment interactions (GxE) could shed light on underlying etiologic mechanisms in this psychiatric condition. Several studies, focused on the role of GxE and conducted by indirect genotype determination, provide evidence of an interaction between genetic susceptibility to schizophrenia and environmental factors such as obstetric complications (OC). Research oriented to identify genetic variations that interact with environmental factors indicates that the risk of schizophrenia might be affected by interaction between OC, cannabis use and schizophrenia candidate genes, like AKT1 and COMT. These studies do not clearly highlight the mechanism by which genes and environment might interact in schizophrenia etiopathogenesis. We think that this mechanism might be easier to understand by focusing on the effect of GxE on intermediate phenotypes related to fundamental aspects of brain development and function. Aim of the study: We analysed how the SNP rs4680 (G > A) of COMT gene and chronic stress interact in modulating the prefrontal neuronal activity during working memory and we found that the effect of stress on prefrontal physiology is conditional on COMT genotype. Conclusions: This result provides further support on the role of the COMT gene in schizophrenia etiopathogenesis, since, in subjects genotyped as GG, stress might reduce neuronal efficiency in the prefrontal cortex, favouring the onset of the illness. The research on GxE, and, in particular, on the role of epigenetic variations in mediating these interactions, could help in explaining and preventing schizophrenia.