Reduced hippocampal volume unmasks distinct impacts of cumulative adverse childhood events (ACEs) on psychotic-like experiences in late childhood and early adolescence.

Stress is associated with increased vulnerability to psychosis, yet the mechanisms that contribute to these effects are poorly understood. Substantial literature has linked reduced hippocampal volume to both psychosis risk and early life stress. However, less work has explored the direct and indirect effects of stress on psychosis through the hippocampus in preclinical samples- when vulnerability for psychosis is accumulating. The current paper leverages the Adolescent Brain Cognitive Development (ABCD) Study sample to examine whether objective psychosocial stressors, specifically adverse childhood experiences (ACE), are linked to vulnerability for psychosis, measured by psychotic-like experiences (PLE) severity, in late childhood and early adolescence, both directly and indirectly through the deleterious effects of stress on the hippocampus. Baseline data from 11,728 individuals included previously examined and validated items to assess ACE exposure, hippocampal volume, and PLE severity - a developmentally appropriate metric of risk for psychosis. Objective psychosocial stress exposure in childhood was associated with elevated PLE severity during the transition from childhood to adolescence. Hippocampal volume was significantly reduced in individuals with greater PLE severity and greater childhood stress exposure compared to peers with low symptoms or low stress exposure. These findings are consistent with a hippocampal vulnerability model of psychosis risk. Stress exposure may cumulatively impact hippocampal volume and may also reflect a direct pathway of psychosis risk. Objective psychosocial stress should be considered as a treatment target that may impact neurodevelopment and psychosis risk.