Genetic risk-dependent brain markers of resilience to childhood Trauma
Resilience to developing emotional disorders is critical for adolescent mental health, especially following childhood trauma. Yet, brain markers of resilience remain poorly understood. By analyzing brain responses to angry faces in a large-scale longitudinal adolescent cohort (IMAGEN), we identified two functional networks located in the orbitofrontal and occipital regions. In girls with high genetic risks for depression, higher orbitofrontal-related network activation was associated with a reduced impact of childhood trauma on emotional symptoms at age 19, whereas in those with low genetic risks, lower occipital-related network activation had a similar association. These findings reveal genetic risk-dependent brain markers of resilience (GRBMR). Longitudinally, the orbitofrontal-related GRBMR predicted subsequent emotional disorders in late adolescence, which were generalizable to an independent prospective cohort (ABCD). These findings demonstrate that high polygenic depression risk relates to activations in the orbitofrontal network and to resilience, with implications for biomarkers and treatment.
Authors
- Andreas Heinz (ORCID: https://orcid.org/0000-0001-5405-9065)
- Sylvane Desrivières (ORCID: https://orcid.org/0000-0002-9120-7060)
- Hugh P Garavan (ORCID: https://orcid.org/0000-0002-8939-1014)
- Jianfeng Feng (ORCID: https://orcid.org/0000-0002-8890-8288)
- Rüdiger Brühl (ORCID: https://orcid.org/0000-0003-0111-5996)
- Tobias Banaschewski (ORCID: https://orcid.org/0000-0003-4595-1144)
- H. MEI LIU
- Sarah Hohmann (ORCID: https://orcid.org/0000-0002-5175-6698)
- Shitong Xiang (ORCID: https://orcid.org/0000-0002-5513-4714)
- Jean‐Luc Martinot (ORCID: https://orcid.org/0000-0002-0136-0388)
- Edmund T. Rolls (ORCID: https://orcid.org/0000-0003-3025-1292)
- Marie‐Laure Paillère Martinot (ORCID: https://orcid.org/0000-0002-0452-2450)
- Barbara Jacquelyn Sahakian (ORCID: https://orcid.org/0000-0001-7352-1745)
- Arun L.W. Bokde (ORCID: https://orcid.org/0000-0003-0114-4914)
- Juliane H. Fröhner (ORCID: https://orcid.org/0000-0002-8493-6396)
- Qiang Luo (ORCID: https://orcid.org/0000-0002-0426-6039)
- Nathalie E. Holz (ORCID: https://orcid.org/0000-0002-6225-9267)
- Herta Flor (ORCID: https://orcid.org/0000-0003-4809-5398)
- Antoine Grigis (ORCID: https://orcid.org/0000-0001-7984-3710)
- Robert Whelan (ORCID: https://orcid.org/0000-0002-2790-7281)
- Henrik Walter (ORCID: https://orcid.org/0000-0002-9403-6121)
- Tianye Jia (ORCID: https://orcid.org/0000-0001-5399-2953)
- Hervé Lemaître (ORCID: https://orcid.org/0000-0002-5952-076X)
- Michael N. Smolka (ORCID: https://orcid.org/0000-0001-5398-5569)
- Dimitri Papadopoulos Orfanos (ORCID: https://orcid.org/0000-0002-1242-8990)
- Dan Joseph Stein (ORCID: https://orcid.org/0000-0001-7218-7810)
- Frauke Nees (ORCID: https://orcid.org/0000-0002-7796-8234)
- Eric Artiges A (ORCID: https://orcid.org/0000-0003-4461-7646)
- Chao Xie (ORCID: https://orcid.org/0000-0002-9137-3835)
- Günter Schumann (ORCID: https://orcid.org/0000-0002-7740-6469)
- Luise Poustka
- Lu Han
- Nilakshi Vaidya (ORCID: https://orcid.org/0000-0002-4600-7158)
- Nan Wang (ORCID: https://orcid.org/0009-0001-3237-5339)
Institutions
- South African Medical Research Council (ZA)
- University of Vermont (US)
- Physikalisch-Technische Bundesanstalt (DE)
- Centre National de la Recherche Scientifique (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- University of Cape Town (ZA)
- University of Mannheim (DE)
- King's College London (GB)
- Trinity College Dublin (IE)
- Heidelberg University (DE)
- University of Cambridge (GB)
- Fudan University (CN)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- XinHua Hospital (CN)
- University Hospital Heidelberg (DE)
- University of Manchester (GB)
- Christian-Albrechts-Universität zu Kiel (DE)
- Humboldt-Universität zu Berlin (DE)
- University of Warwick (GB)
- Sorbonne Université (FR)
- Shanghai Institute for Science of Science (CN)
- Institut des Maladies Neurodégénératives (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Central Institute of Mental Health (DE)
- Oxford Centre for Computational Neuroscience (GB)
- Shanghai Research Center for Acupuncture and Meridians (CN)
- Pitié-Salpêtrière Hospital (FR)
- CEA Paris-Saclay (FR)
- Laboratoire de Biologie et Pharmacologie Appliquée (FR)
- Children's Hospital of Fudan University (CN)
- Shanghai Children's Hospital (CN)
- Einstein Center for Neurosciences Berlin (DE)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- Freie Universität Berlin (DE)
- Technische Universität Dresden (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-05
- DOI
- https://doi.org/10.1038/s41467-025-61471-0
- Citations
- 1
- Primary Topic
- Resilience and Mental Health
- Type
- article
- Field-Weighted Citation Impact
- 2.31
Funders
- Fondation de l'Avenir pour la Recherche Médicale Appliquée
- National Institute for Health and Care Research
- King's College London
- European Commission
- Science Foundation Ireland
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- National Natural Science Foundation of China
- Bundesministerium für Bildung und Forschung
- Fondation pour la Recherche Médicale
- Fondation de France
- Fédération pour la Recherche sur le Cerveau
- Mission Interministérielle de Lutte Contre les Drogues et les Conduites Addictives
- National Institutes of Health
- Medical Research Council
- Program of Shanghai Academic Research Leader