Poster #S59 DECREASED GREY MATTER VOLUME AS THE EXPRESSION OF DIFFERENTIAL SENSITIVITY TO ENVIRONMENTAL RISK EXPOSURE IN PSYCHOTIC DISORDER

Abstract

Background: Cannabis use, childhood trauma and urban upbringing are important risk factors for psychotic disorder. Differential sensitivity to these environmental exposures may be expressed as structural brain alterations. The aim of this study was to examine whether cannabis use, childhood trauma and urban upbringing are associated with alterations in gray matter volume (GMV) and whether this is dependent on different genetic risk levels for psychotic disorder. Methods: T1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 98 healthy siblings of patients with psychotic disorder and 87 controls. Freesurfer software was used to measure GMV. Cannabis use was assessed with the Composite International Diagnostic Interview and a urine test. Childhood trauma was measured with the Childhood Trauma Questionnaire Short Form. The developmental urbanicity exposure comprised 5 levels, reflecting the average population density between birth and the 15th birthday. Multilevel random regression analyses were used to examine the association between group and environment (as well as their interaction) on the one hand and GMV as the dependent variable on the other. The three-way interaction group x environment x sex was also investigated. Results: There were significant main effects of group (B=−10.44, p=0.04) and cannabis (B=−8.18, p<0.05) on GMV, which was not the case for childhood trauma and urbanicity. Both the two-way interaction between group and cannabis (χ2=5.31, p=0.07) and between group and childhood trauma (χ2=10.32, p=0.01) in the model of GMV were significant. Stratified analyses showed that cannabis use and childhood trauma were associated with lower GMV in the patient group (cannabis use: B=−14.89, p=0.03; childhood trauma: B linear trend = −8.58, p=0.04). Although three way interactions (group x cannabis or childhood trauma x sex) were inconclusive, environmental effects on GMV were found in male patients (cannabis: B=−24.86, p<0.01; childhood trauma: B linear trend = −12.16, p=0.02) and not in female patients. The two-way interaction between group and developmental urbanicity was not significant (χ2=1.79, p=0.41). Discussion: The findings suggest that exposure to cannabis and childhood trauma, but not urban upbringing, may impact global GMV in individuals at the highest genetic risk level for psychotic disorder. Thus, patients may be more sensitive to cannabis and childhood trauma, expressed as a reduction in GMV, than individuals at higher than average (siblings) or average (controls) genetic risk. This increased cerebral sensitivity to cannabis and trauma may be confined to male patients.