Interaction between childhood adversity and functional polymorphisms in the dopamine pathway on first-episode psychosis

Background: There is consistent evidence of a cumulative relationship between childhood adversity and psychosis, with number of adversities experienced increasing the probability of psychosis onset. It is possible that genetic factors moderate the association between childhood adversity and psychosis, potentially by influencing how an individual reacts biologically and/or psychologically following exposure to adversity, in such a way as to set them off on the path to psychosis. However, identifying the specific genetic variants involved and how they interact with childhood adversity remains challenging. We examined whether the association between cumulative exposure to childhood adversity and development of psychotic disorder was moderated by the COMT Val158Met, AKT1 rs2494732 or DRD2 rs1076560 polymorphisms, known to affect dopamine levels. Methods: Participants were 285 first-presentation psychosis cases and 256 geographically-matched controls drawn from the Genetics and Psychosis (GAP) study. Childhood adversity was assessed using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and blood- and cheek-derived genotype data were collected. Results: Our findings revealed no main effect of COMT Val158Met, AKT1 rs2494732 and DRD2 rs1076560 polymorphisms on psychosis case status or reports of childhood adversity. Individuals reporting a history of multiple adversities were more likely to be psychosis patients than controls, regardless of their genetic risk. There was no evidence of candidate genotype by childhood adversity interactions in relation to psychosis onset. Conclusion: These findings did not provide evidence of a possible role of COMT Val158Met, AKT1 rs2494732 or DRD2 rs1076560 genotypes in modifying the association between childhood adversity and onset of psychosis.