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.
| Title: | 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. |
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| Authors: | Wang HR; Department of Psychology, University of California Los Angeles, Los Angeles, California; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California.; Liu ZQ; Montréal Neurological Institute, McGill University, Montréal, Québec, Canada.; Pozzi E; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia.; Hussain A; Brain Imaging and Analysis Center, Duke University, Durham, North Carolina.; Sigar P; Department of Psychiatry and Behavioral Sciences, University of California Los Angeles, Los Angeles, California.; Abdallah C; Department of Psychiatry, Baylor College of Medicine, Houston, Texas; Department of Psychiatry, Yale University, New Haven, Connecticut.; Alexander N; Department of Psychiatry, University of Marburg, Marburg, Germany.; Baker J; McLean Hospital, Belmont, Massachusetts; Harvard Medical School, Boston, Massachusetts.; Bauer J; Clinic for Radiology, University of Münster, Münster, Germany.; Blackford JU; Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.; Cisler J; University of Texas at Austin, Austin, Texas.; Connolly CG; Department of Biomedical Sciences, Florida State University, Tallahassee, Florida.; Cotton A; Division of Cognitive Neuroscience, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Daniels J; Department of Clinical Psychology, University of Groningen, Groningen, the Netherlands; Trauma Centrum Beilen, Geestelijke Gezondheidszorg Drenthe, Beilen, the Netherlands.; Dannlowski U; Institute for Translational Psychiatry, University of Münster, Münster, Germany.; Densmore M; Department of Psychiatry, Western University, London, Ontario, Canada; Imaging Division, Lawson Research Institute, London, Ontario, Canada.; deRoon-Cassini T; Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin; Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, Wisconsin.; Dima D; Department of Psychology, City St. George's, University of London, London, United Kingdom; Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.; Du Plessis S; Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.; Etkin A; Stanford University, Stanford, California.; Fani N; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia.; Fisch L; Institute for Translational Psychiatry, University of Münster, Münster, Germany.; Fitzgerald J; Department of Psychology, Marquette University, Milwaukee, Wisconsin.; Frodl T; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital Aachen, Aachen, Germany.; Fu CHY; Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Psychology, University of East London, London, United Kingdom.; Gonul AS; Department of Psychiatry, Ege Üniversitesi School of Medicine, Izmir, Turkey.; Gordon EM; Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.; Gotlib IH; Department of Psychology, Stanford University, Stanford, California.; Goya-Maldonado R; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.; Groenewold NA; Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Grotegerd D; Institute for Translational Psychiatry, University of Münster, Münster, Germany.; Hahn T; Institute for Translational Psychiatry, University of Münster, Münster, Germany.; Hamilton JP; Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.; Han LKM; Department of Psychiatry, Amsterdam University Medical Center location, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Mood, Anxiety, Psychosis, Sleep and Stress program, Amsterdam Neuroscience, Amsterdam, the Netherlands; Mental Health program, Amsterdam Public Health, Amsterdam, the Netherlands.; Harpaz-Rotem I; Departments of Psychiatry and of Psychology, Yale University, New Haven, Connecticut.; Haswell CC; Brain Imaging and Analysis Center, Duke University, Durham, North Carolina; Clinical Neuroscience Division, National Center for PTSD, Veterans Affairs (VA) Connecticut Healthcare System, West Haven, Connecticut.; Herringa R; Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.; Herzog J; Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.; Ipser J; Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Jahanshad N; Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California.; Jovanovic T; Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan.; Kaufman M; McLean Hospital, Belmont, Massachusetts; Harvard Medical School, Boston, Massachusetts.; Kircher T; Department of Psychiatry, University of Marburg, Marburg, Germany.; Konowski M; Institute for Translational Psychiatry, University of Münster, Münster, Germany.; Koopowitz SM; Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Krug A; Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.; Krystal J; Clinical Neuroscience Division, National Center for PTSD, Veterans Affairs (VA) Connecticut Healthcare System, West Haven, Connecticut; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.; Lanius R; Department of Neuroscience, Western University, London, Ontario, Canada.; Larson C; Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin.; Lazarov A; School of Psychological Science, Tel Aviv University, Tel Aviv, Israel; Irving Medical Center, Columbia University, New York, New York.; Lebois L; McLean Hospital, Belmont, Massachusetts; Harvard Medical School, Boston, Massachusetts.; Leehr E; Institute for Translational Psychiatry, University of Münster, Münster, Germany.; Levy I; Departments of Comparative Medicine, Neuroscience, and Psychology, Yale University, New Haven, Connecticut.; Li M; Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany.; Manthey A; Health and Medical University Potsdam, Potsdam, Germany; Charité Universitätsmedizin Berlin Campus Charité Mitte: Charité Universitätsmedizin Berlin, Berlin, Germany.; Maron-Katz A; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.; McIntosh AM; Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.; McLaughlin KA; Department of Psychology, Harvard University, Cambridge, Massachusetts; Ballmer Institute for Children's Behavioral Health, University of Oregon, Eugene, Oregon.; Meinert S; Institute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.; Mwangi B; Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas; School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston, Texas.; Nelson SM; Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, Minnesota.; Nenadić I; Department of Psychiatry, University of Marburg, Marburg, Germany.; Neria Y; Irving Medical Center, Columbia University, New York, New York.; Neufeld R; Departments of Psychology and Psychiatry, Neuroscience Program, Western University, London, Ontario, Canada; Department of Psychology, University of British Columbia, Kelowna, British Columbia, Canada.; Ojha A; Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania.; Olatunji BO; Department of Psychology, Vanderbilt University, Nashville, Tennessee.; Olson EA; Crisis Text Line, New York, New York.; Opel N; Institute for Translational Psychiatry, University of Münster, Münster, Germany; German Center for Mental Health, Berlin, Germany.; Peverill M; Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.; Ressler K; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.; Ross M; Northwestern University, Evanston, Illinois.; Rosso I; Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.; Sacchet MD; Meditation Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.; Sambrook K; University of Washington, Seattle, Washington.; Schmahl C; Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; German Center for Mental Health, Partner Site Mannheim-Heidelberg-Ulm, Mannheim, Germany.; Seedat S; Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.; Shenton ME; Department of Psychiatry, Mass General Brigham, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.; Sicorello M; Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; German Center for Mental Health, Partner Site Mannheim-Heidelberg-Ulm, Mannheim, Germany.; Sierk A; Charité Universitätsmedizin Berlin Campus Charité Mitte: Charité Universitätsmedizin Berlin, Berlin, Germany.; Soares JC; Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas; School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston, Texas.; Stein DJ; South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.; Stein F; Department of Psychiatry, University of Marburg, Marburg, Germany.; Stein MB; Department of Psychiatry, University of California San Diego, La Jolla, California.; Suarez-Jimenez B; Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York.; Théberge J; Department of Psychiatry, Western University, London, Ontario, Canada; Imaging Division, Lawson Research Institute, London, Ontario, Canada.; Thomopoulos SI; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.; Tomas C; Comprehensive Injury Center, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Epidemiology and Social Sciences, Institute of Health and Humanity, Medical College of Wisconsin, Milwaukee, Wisconsin.; Usemann P; Department of Psychiatry, University of Marburg, Marburg, Germany.; van den Heuvel LL; Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Unit on the Genomics of Brain Disorders, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.; van Rooij SJH; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia.; Walter H; Division of Mind and Brain Research, Department for Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.; Walter M; Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany; German Center for Mental Health, Partner Site Halle-Jena-Magdeburg, Jena, Germany.; Wang X; Department of Neuroscience and Psychiatry, University of Toledo, Toledo, Ohio.; Whalley HC; Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.; Winter NR; Institute for Translational Psychiatry, University of Münster, Münster, Germany.; Wu MJ; Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas; School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston, Texas.; Xie H; Department of Neuroscience and Psychiatry, University of Toledo, Toledo, Ohio.; Yang TT; Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco School of Medicine, San Francisco, California.; Zhu X; Department of Bioengineering, University of Texas at Arlington, Arlington, Texas.; Zilcha-Mano S; School of Psychological Science, University of Haifa, Haifa, Israel.; Zunta-Soares GB; Center of Excellence on Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas; School of Behavioral Health Sciences, University of Texas Health Science Center at Houston, Houston, Texas.; Frangou S; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.; Thompson PM; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.; Salminen L; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.; Sun D; Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, North Carolina; Brain Imaging Analysis Center, Duke University, Durham, North Carolina; Department of VA Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, North Carolina.; Morey R; Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, North Carolina; Brain Imaging Analysis Center, Duke University, Durham, North Carolina; Department of VA Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, North Carolina.; Stevens JS; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Atlanta VA Medical Center, Atlanta, Georgia.; Schmaal L; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia.; Ho TC; Department of Psychology, University of California Los Angeles, Los Angeles, California; Department of Psychiatry and Behavioral Sciences, University of California Los Angeles, Los Angeles, California. Electronic address: tiffanycho@ucla.edu. |
| Source: | Biological psychiatry [Biol Psychiatry] 2026 Mar 05. Date of Electronic Publication: 2026 Mar 05. |
| Publication Model: | Ahead of Print |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0213264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2402 (Electronic) Linking ISSN: 00063223 NLM ISO Abbreviation: Biol Psychiatry Subsets: MEDLINE |
| Imprint Name(s): | Publication: New York, NY : Elsevier; Original Publication: New York, Plenum Pub. Corp. |
| 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.; (Copyright © 2026 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) |
| Comments: | Update of: bioRxiv. 2025 Jun 08:2025.06.04.657717. doi: 10.1101/2025.06.04.657717.. (PMID: 40661416) |
| Contributed Indexing: | Keywords: Brain morphometry; Childhood maltreatment; Major depressive disorder; Normative modeling; PTSD; Sex differences |
| Entry Date(s): | Date Created: 20260306 Latest Revision: 20260520 |
| Update Code: | 20260520 |
| DOI: | 10.1016/j.biopsych.2026.02.016 |
| PMID: | 41791639 |
| Database: | MEDLINE |
Journal Article