Life Event Stress and Reduced Cortical Thickness in Youth at Clinical High-Risk for Psychosis and Healthy Youths

Abstract Background A decline in cortical thickness during early life appears to be a normal neuromaturational process. Accelerated cortical thinning has been linked with conversion to psychosis among individuals at clinical high-risk for psychosis (CHR-P). Previous research indicates that exposure to life event stress (LES) is associated with exaggerated cortical thinning in both healthy and clinical populations, and LES is also linked with conversion to psychosis in CHR-P. To date, there are no reports on the relationship of LES with cortical thickness in CHR-P. The present study examines this relationship and whether LES is linked with cortical thinning to a greater degree in CHR-P who convert to psychosis compared to CHR-P who do not convert and healthy controls. Methods Controlling for age and gender (364 male, 262 female), the present study examined associations between LES and baseline cortical thickness in 436 CHR-P (375 non-converters and 61 converters) and 190 comparison subjects in the North American Prodrome Longitudinal Study. Results Findings indicate that pre-baseline cumulative LES is associated with reduced baseline cortical thickness in several regions among the CHR-P and control groups. Evidence suggests that LES is a risk factor for thinner cortex to the same extent across diagnostic groups, while CHR-P status is linked with thinner cortex in select regions after accounting for LES. Conclusions This research provides additional evidence to support the role of LES in cortical thinning in both healthy youth and those at CHR-P. Potential underlying mechanisms of the findings and implications for future research are discussed.