UC San Diego

Rationale: Childhood adversity is strongly associated with increased risk for psychosis. Despite clear evidence for an association between childhood trauma (CT) and psychosis, the biological mechanisms that mediate the relationship between CT and clinical outcomes in psychosis remain largely unknown. The aim of this study is to better understand associations between inflammation, CT, and clinical outcomes in subjects identified to be at clinical high risk for developing psychosis (CHR) and evaluate whether inflammation mediates the relationship between CT and clinical outcomes.

Design and Methods: Participants included 67 CHR subjects and 34 unaffected comparison subjects (UC; N = 101) ages 12-35 who participated in the North American Prodrome Longitudinal Study 2 (NAPLS2). Experience of CT was assessed using the Childhood Trauma and Abuse Scale. Severity of psychosis-risk symptoms was measured using the Structured Interview for Prodromal Syndromes (SIPS). Functioning was assessed using Global Assessment of Functioning (GAF) scale. Blood samples were analyzed using validated multiplex immunoassay. Group differences between UC and CHR in CT, functioning, psychosis risk symptom severity, and inflammation were evaluated using independent samples t-tests and Chi-squared tests. Two mediation models were tested to explore whether inflammation mediated the association between 1. total CT and GAF and 2. total CT and psychosis risk positive symptom severity.

Results: Compared to UC, CHR subjects demonstrated significantly higher incidence of total CT, greater severity of psychosis risk symptoms, and significantly lower global, role, and social functioning. Regression analyses revealed that total CT and a 15-Analyte Inflammatory Index uniquely predicted psychosis risk positive symptom severity (β = 0.24, t(65) = 1.9, p = 0.05) and GAF scores (β = -0.26, t(65) =-2.25, p = 0.03). Combined, these variables explained a significant proportion of variance in psychosis risk positive symptom severity (R2 = 0.122) and GAF (R2 = 0.151) scores.

Conclusions and Clinical Implications: The relationship between CT, increased psychosis-risk symptom severity, and decreased functioning was replicated in this study and results demonstrated novel associations between total CT, psychosis risk positive symptom severity, and GAF. This is the first study to demonstrate that CT and inflammation may have unique and additive effects on increased psychosis risk positive symptom severity and reduced global functioning in individuals at CHR for psychosis.