The impact of genes by childhood adversity interaction on the clinical and social outcomes of psychosis

Abstract

A history of childhood adversity is associated with adult psychotic disorder but it is not known why only some exposed individuals go on to develop psychosis and what their outcomes are. This study aimed to explore the association between specific forms of childhood adversity and the presence, and one-year outcomes, of psychosis and the interplay with familial liability, candidate genes and polygenic risk scores. Data on 285 first-presentation psychosis cases and 256 geographically-matched controls drawn from the Genetic and Psychosis (GAP) study was utilised. Childhood adversity exposure was assessed using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q), family psychiatric history with the Family Interview for Genetic Studies (FIGS) and genetic information was extracted from blood and buccal samples. The Psychiatric and Personal History Schedule (PPHS) and the Global Assessment of Functioning Scale (GAF) were completed from clinical records to ascertain clinical and social outcomes in the cases over the first year since initial presentation to psychiatric services for psychosis. Separation from mother or father (for at least 6 months) before the age of 17 years demonstrated the most robust association with psychotic disorder after controlling for all confounders including parental history of psychosis (Adj.OR=2.22, 95% CI: 1.52-3.27, p<0.001) and was also associated with longer psychiatric admissions (Adj.OR=2.45, 95% CI: 1.06-5.66, p=0.035) and noncompliance with antipsychotic medications (Adj.OR=2.34, 95% CI: 1.11-4.92, p=0.026) at one-year follow-up. There was no evidence for interaction between any type of childhood adversity and either family psychiatric history or candidate genes in relation to either the presence or one-year outcomes of psychosis. However, a pilot study on a subsample of 86 psychosis cases and 110 community controls of Caucasian parentage revealed an interaction between a schizophrenia polygenic risk score and parental separation, parental loss and sexual abuse for the presence of psychosis (all p<0.001).

Date of Award	2016
Original language	English
Awarding Institution	King's College London
Supervisor	Helen Fisher (Supervisor) & Robin Murray (Supervisor)