Childhood Maltreatment and Deviations from Normative Brain Structure: Results from 3,711 Individuals from the ENIGMA MDD and ENIGMA PTSD

Childhood maltreatment (CM), encompassing abuse and neglect, affects over two-thirds of the general population and increases risk for stress-related psychopathology, including major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). The extent to which neuroanatomical alterations in MDD and PTSD are attributable to CM, however, is uncertain. Here, we analyzed CM and 3D structural brain MRI data from 3,711 participants in the ENIGMA MDD and PTSD Working Groups (25 sites; 33.3+/-13.0 years; 59.9% female). Normative modeling estimated deviation z-scores for 14 subcortical volumes (SV), 68 cortical thickness (CT), and 68 surface area (SA) measures, capturing differences from population norms. Transdiagnostic associations between CM and brain deviation scores were evaluated within each sex and age cohort. In young adults (ages 18-35), abuse was associated with larger volumes in thalamus and pallidum, thinner isthmus cingulate and middle frontal regions, and thicker medial orbitofrontal cortex; there were no significant effects in pediatric (≤18 years) participants. The strongest effects were observed in young female adults (|β|=.07-.22, q<.05): greater abuse and neglect were correlated with smaller hippocampus and putamen volumes, thinner entorhinal cortex, and smaller SA in fusiform/inferior parietal regions, and with larger SA in orbitofrontal and occipital cortices. In males, abuse had widespread effects on CT and SA (|β|=.1-.18, q<.05); effects for neglect were minimal. Our findings of age- and sex-specific instantiations of CM on brain morphometry highlight the importance of developmental context in understanding how adverse experiences shape neurobiological vulnerability to MDD and PTSD.