Document Type

Article

Publication Date

3-2026

Publisher

Elsevier

Source Publication

Biological Psychiatry

Source ISSN

0006-3223

Abstract

Background. Childhood maltreatment (CM), encompassing abuse and neglect, is highly prevalent and associated with elevated risk for major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and other related conditions. However, the extent to which neuroanatomical alterations in MDD and PTSD are attributable to CM is uncertain.

Methods. Here, we analyzed CM and whole-brain magnetic resonance imaging (MRI) data from 3711 participants in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) MDD and PTSD Working Groups (25 sites; mean age = 33.3 ± 13.0 years; 59.9% female). Normative modeling estimated deviation z scores for 14 subcortical volume, 68 cortical thickness (CT), and 68 surface area (SA) measures. To identify transdiagnostic effects, associations between CM and brain deviation scores were evaluated across all participants (patients and healthy control participants) stratified by sex and 3 age bins (pediatric, young adult, older adult).

Results. In young adults (ages 18–35), abuse was associated with larger volumes in the 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| = 0.07–0.22, 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 the orbitofrontal and occipital cortices. In males, abuse had widespread effects on CT and SA (|β| = 0.1–0.18, q < .05); effects for neglect were minimal.

Conclusions. 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.

Comments

Published version. Biological Psychiatry (2026): 1-27. DOI. © 2026 Elsevier. Used with permission.

Complete list of authors available on the attached document.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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