Abstract
INTRODUCTION: Adverse childhood experiences (ACEs) are linked to higher rates of psychiatric disorders in adults. Previous neuroimaging studies with small samples have shown associations between ACEs and alterations in brain volume, connectivity, and blood flow. However, no study has explored these associations in a large clinical population to identify brain regions that may mediate the relationship between ACEs and psychiatric diagnoses. This study aims to evaluate how patient-reported ACEs are associated with brain function in adults, across diagnoses. METHODS: We analyzed 7,275 adults using HMPAO SPECT scans at rest and during a continuous performance task (CPT). We assessed the impact of ACEs on brain function across psychiatric diagnoses and performed mediation analyses where brain functional regions of interest acted as mediators between patient-reported ACEs and specific psychiatric diagnoses. We further evaluated the risk of being diagnosed with specific classes of mental illnesses as a function of increasing ACEs and identified which specific ACE questions were statistically related to each diagnosis in this cohort. RESULTS: Increased ACEs were associated with higher activity in cognitive control and default mode networks and decreased activity in the dorsal striatum and cerebellum. Higher ACEs increased the risk of anxiety-related disorders, substance abuse, and depression. Several brain regions were identified as potential mediators between ACEs and adult psychiatric diagnoses. DISCUSSION: This study, utilizing a large clinical cohort, provides new insights into the neurobiological mechanisms linking ACEs to adult psychiatric conditions. The findings suggest that specific brain regions mediate the effects of ACEs on the risk of developing mental health disorders, highlighting potential targets for therapeutic interventions.