Abstract
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis.
Highlights
One widely replicated environmental risk factor for psychosis is exposure to adverse experiences in childhood [1,2], such as physical or sexual abuse, or parental separation
We have previously shown in this sample that different forms of childhood adversity are associated with presence of psychotic disorder [11], and that a schizophrenia polygenic risk score for schizophrenia (PRS) accounts for 9% of the liability to psychotic disorder [24]
The sample was drawn from cases and controls who participated in the Genetics and Psychosis (GAP) study from the Lambeth, Southwark, Lewisham and Croydon adult in-patient and outpatient units of the South London & Maudsley (SLAM) Mental Health National Health Service (NHS) Foundation Trust
Summary
One widely replicated environmental risk factor for psychosis is exposure to adverse experiences in childhood [1,2], such as physical or sexual abuse, or parental separation. The literature suggests that adversities are damaging if they are overwhelming and persistent, as demonstrated by a high rate of multiple childhood traumatic experiences in people with psychosis [3]. It is not known why only a small proportion of individuals who experience adversity in childhood later develop psychosis. Two studies have investigated the interplay between childhood adversity and familial risk for mental health problems in a first-episode psychosis sample [10,11] and found no evidence of gene-environment interaction. Interactions between potential molecular genetic susceptibility and exposure to childhood adversity in predicting development of psychosis have mainly focused on candidate genes such as FKBP5 [12,13], BDNF [14,15], and COMT [16]
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