Gene-environment interaction as a predictor of early adjustment in first episode psychosis

This study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development.

We constructed a schematic 'two-hit' model, with Val/Val homozygosity for the catechol-O-methyltransferase (COMT) Val158Met polymorphism as the 'first hit' and history of obstetric complications and parental socioeconomic status as 'second hits'. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study population comprised 221 adolescents and adults with FEP and 191 sex- and age-matched controls.

The interaction between the Val/Val COMT genotype and a positive history of obstetric complications plus low parental socioeconomic status was significantly associated with poorer early adjustment. These results were observed both in FEP individuals and in controls, and remained significant after controlling for age, sex, and diagnosis.

Individuals carrying Val/Val seem to be more sensitive to the synergistic effect of environmental factors acting early in neurodevelopment, which leads to vulnerability phenotypes such as impaired early adjustment.