Distinct neural moderators of resilience and vulnerability confer heterogeneous outcomes following early-life adversity

Abstract

Early-life adversity (ELA) increases risk for psychiatric disorders, but outcomes are highly variable. Using multimodal neuroimaging and computational moderation in large adolescent cohorts, we systematically identify brain features that buffer or amplify effects of three ELA subtypes--familial interpersonal, non-familial interpersonal, and non-interpersonal adversity--on transdiagnostic psychopathology. Multimodal neural moderators were subtype- and pathology dimension-specific, revealing distinct neurobiological mechanisms moderating heterogeneous outcomes. Protective features clustered in limbic, sensory integration, and regulatory circuits (amygdala, parietal cortex, anterior cingulate), while vulnerability features concentrated in frontotemporal circuits. Individual features and a new Relative Resilience Index (RRI)--reflecting the individual balance between protective and vulnerability features across the whole-brain--prospectively predicted psychopathological progression over two years, linking brain signatures to future mental health trajectories. Findings establish the brain as dynamic moderator of distinct adversity effects and introduce a system-level marker for risk stratification, advancing mechanistic precision in youth mental health and guiding early intervention.