Childhood Maltreatment and Deviations From Normative Brain Structure: A Mega-Analysis of 3711 Individuals From the ENIGMA Major Depressive Disorder and ENIGMA Posttraumatic Stress Disorder Working Groups
Year: 2026
Type: review
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.
Source: Biological Psychiatry
Authors: Haley R. Wang, Zhen-Qi Liu, Elena Pozzi, Ahmed Hussain, Priyanka Sigar, Chadi Abdallah, Nina Alexander, Justin Baker, Jochen Bauer, Jennifer Urbano Blackford, Josh Cisler, Colm G. Connolly, Andrew Cotton, Judith Daniels, Udo Dannlowski, Maria Densmore, Terri deRoon-Cassini, Danai Dima, Stefan Du Plessis, Amit Etkin, Negar Fani, Lukas Fisch, Jacklynn Fitzgerald, Thomas Frodl, Cynthia H.Y. Fu, Ali Saffet Gonul, Evan M. Gordon, Ian H. Gotlib, Roberto Goya-Maldonado, Nynke A. Groenewold, Dominik Grotegerd, Tim Hahn, J. Paul Hamilton, Laura K.M. Han, Ilan Harpaz-Rotem, Courtney C. Haswell, Ryan Herringa, Julia Herzog, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa Kaufman, Tilo Kircher, Maximilian Konowski, Sheri-Michelle Koopowitz, Axel Krug, John Krystal, Ruth Lanius, Christine Larson, Amit Lazarov, Lauren Lebois, Elisabeth Leehr, Ifat Levy, Meng Li, Antje Manthey, Adi Maron-Katz, Andrew M. McIntosh, Katie A. McLaughlin, Susanne Meinert, Benson Mwangi, Steven M. Nelson, Igor Nenadić, Yuval Neria, Richard Neufeld, Amar Ojha, Bunmi O. Olatunji, Elizabeth A. Olson, Nils Opel, Matthew Peverill, Kerry Ressler, Marisa Ross, Isabelle Rosso, Matthew D. Sacchet, Kelly Sambrook, Christian Schmahl, Soraya Seedat, Martha E. Shenton, Maurizio Sicorello, Anika Sierk, Jair C. Soares, Dan J. Stein, Frederike Stein, Murray B. Stein, Benjamin Suarez-Jimenez, Jean Théberge, Sophia I. Thomopoulos, Carissa Tomas, Paula Usemann, Leigh L. van den Heuvel, Sanne J.H. van Rooij, Henrik Walter, Martin Walter, Xin Wang, Heather C. Whalley, Nils R. Winter, Mon-Ju Wu, Hong Xie, Tony T. Yang, Xi Zhu, Sigal Zilcha-Mano, Giovana B. Zunta-Soares, Sophia Frangou, Paul M. Thompson, Lauren Salminen, Delin Sun, Rajendra Morey, Jennifer S. Stevens, Lianne Schmaal, Tiffany C. Ho
Institutions: University of California, Los Angeles, Montreal Neurological Institute and Hospital, McGill University, The University of Melbourne, Orygen, Duke University, Baylor College of Medicine, Yale University, Philipps University of Marburg, Harvard University, McLean Hospital, University of Münster, University Hospital Münster, University of Nebraska Medical Center, Vanderbilt University Medical Center, The University of Texas at Austin, Florida State University, Johns Hopkins University, Johns Hopkins Medicine, University of Groningen, Western University, Lawson Health Research Institute, Lawson Research Institute, Medical College of Wisconsin, King's College London, City St George's, University of London, South African Medical Research Council, Stellenbosch University, Stanford University, Emory University, Marquette University, Universitätsklinikum Aachen, University of East London, Ege University, Washington University in St. Louis, Universitätsmedizin Göttingen, University of Cape Town, University of Bergen, Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, VA Connecticut Healthcare System, National Center for Post Traumatic Stress Disorder, University of Wisconsin–Madison, Heidelberg University, Central Institute of Mental Health, University of Southern California, Wayne State University, University Hospital Bonn, University of Wisconsin–Milwaukee, Tel Aviv University, Columbia University Irving Medical Center, Columbia University, Jena University Hospital, HMU Health and Medical University, Charité – Universitätsmedizin Berlin, Stanford Medicine, University of Edinburgh, University of Oregon, The University of Texas Health Science Center at Houston, University of Minnesota, University of British Columbia, University of British Columbia, Okanagan Campus, University of Pittsburgh, Center for the Neural Basis of Cognition, Vanderbilt University, Deutsches Zentrum für Psychische Gesundheit, Northwestern University, Massachusetts General Hospital, University of Washington, Medizinische Fakultät Mannheim, Brigham and Women's Hospital, Mass General Brigham, University of California San Diego, University of Rochester Medicine, University of Rochester, University of Toledo, University of California, San Francisco, University of California San Francisco Medical Center, The University of Texas at Arlington, University of Haifa, Djavad Mowafaghian Centre for Brain Health, Icahn School of Medicine at Mount Sinai, Atlanta VA Medical Center
Language: English
Topic: Child Abuse and Trauma
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $5,489
Funders: U.S. Department of Defense, Bill and Melinda Gates Foundation, Sunovion, Wellcome Trust, International Psychoanalytical Association, National Institute for Health and Care Research, South African Medical Research Council, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Canadian Institute for Military and Veteran Health Research, National Institutes of Health, NIHR Maudsley Biomedical Research Centre, National Center for PTSD, U.S. Department of Veterans Affairs, Canadian Institutes of Health Research, Medical Research Council, Fonds de recherche du Québec – Nature et technologies, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of General Medical Sciences, National Center for Complementary and Integrative Health
Awards: Neural Mechanisms of Cognitive Control in Posttraumatic Stress Disorder, G1191780822, G1438067556, Using Context to Validate and Improve Wrist-Tracking Measures of Eating Activity, G179444772, G2284422223, G238323396, Generalizing polygenic risk prediction methods across populations for insights into psychiatric disease, G2511155013, Exploiting genomic approaches to identify the environmental basis of depression, Neural mechanisms of decision-making under uncertainty in PTSD, G3434867832, G3450339767, G3685900323, G3762292575, G3804724313, Longitudinal MRI study of PTSD development from days to weeks after trauma, Neural mechanisms of meditation training in healthy and depressed adolescents: An MRI connectome study, G4119534169, G4177447136, Integrating 1H MRS with 2H-Labeled Glucose to Characterize Dynamic Glutamate Metabolism in Major Depressive Disorder, G4421633565, The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression, G4539198987, Neural mechanisms of meditation training in healthy and depressed adolescents: An MRI connectome study, G4856762701, Generalizing polygenic risk prediction methods across populations for insights into psychiatric disease, G5142766902, Mechanisms of gene silencing induced by long noncoding RNAs, G5850682332, Identification of Distinct Multimodal Biotypes of PTSD Using Data Driven Approach: A Multisite Big Data Study, G648958512, G6733821374, G8087705, G8166743225, Acute Neurocognitive-affective Predictors of Chronic Post-trauma Outcomes, e:Med Nachwuchsgruppe PreNeSt - Untersuchung von Hirnnetzwerken durch nicht-invasive transkraniale Magnetstimulation zur Therapieoptimierung bei affektiven Störungen, Sleep and emotion processing in adolescent Post-traumatic stress Disorder, ENIGMA World Aging Center, Genomic Architecture of Functional Brain Networks in PTSD, ENIGMA Bipolar Initiative: A Global Study of Imaging Genomics & Clinical Outcomes, Precision mapping of Parkinson's Disease pathophysiology in the Somato-Cognitive Action Network’s DBS targets, The impact of early life adversity on brain network development in youth, Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents with Depression: Toward Predictors of Treatment Response and Clinical Course, Using novel virtual reality tasks to identify neural mechanisms of discrimination learning in PTSD, BNST neurocircuitry in PTSD
OpenAlex ID: W7133851018