The Impact of Stress and Childhood Trauma on Attenuated Psychotic Symptoms and White Matter Integrity

Abstract

Recent studies have found associations between prolonged stress response and white matter (WM) microstructure in individuals with schizophrenia, as well as correlations between early life trauma and WM integrity in individuals with schizophrenia and non-psychiatric controls; however, psychosocial correlates of WM dysfunction have not yet been adequately explored in individuals experiencing attenuated psychotic symptoms (APS, subthreshold versions of positive psychotic symptoms). This study examines WM microstructure using traditional and free-water corrected diffusion metrics within a community sample of 66 16 to 30-year-olds experiencing a range of APS to examine the contribution of perceived stress and childhood trauma to the relationship between APS and WM abnormalities, as well as examine the moderating influence of sex assigned at birth (herein referred to as sex) to these relationships. We found that overall symptom severity on the Structured Interview for Psychosis-risk Syndromes (SIPS) was associated with higher extracellular free-water (FW) across the whole brain, lower free-water corrected fractional anisotropy values (FAT), and higher free-water corrected radial diffusivity (RDT). Further, childhood trauma significantly moderated the relationship between SIPS scores and both FAT and RDT, controlling for biological sex at birth, such that in the presence of APS, childhood trauma was associated with higher FAT and lower RDT, and in lower APS the opposite pattern was seen, with childhood trauma associated with lower FAT and lower RDT. After stratifying for sex, childhood trauma moderated the SIPS – FAT and RDT relationships in males similar to findings in the whole sample, though this relationship was not present in females. Perceived stress was not a significant moderator in the total sample, though was a significant moderator of the APS – FA relationship in males only. This study represents an important step toward identifying mechanisms for WM dysfunction within individuals with psychosis spectrum disorders, as well as identifying important targets for interventions.