Genetic risk-dependent brain markers of resilience to childhood Trauma

Han Lu, Edmund T. Rolls, Hanjia Liu, Dan J. Stein, Barbara J. Sahakian, Rebecca Elliott, Tianye Jia, Chao Xie, Shitong Xiang, Nan Wang, Tobias Banaschewski, Arun L. W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Herve Lemaitre, Luise Poustka, Sarah Hohmann, Nathalie Holz, Juliane H. Fröhner, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Jianfeng Feng and Qiang Luo ()
Additional contact information
Han Lu: Fudan University
Edmund T. Rolls: Oxford Centre for Computational Neuroscience
Hanjia Liu: Fudan University
Dan J. Stein: University of Cape Town
Barbara J. Sahakian: University of Cambridge
Rebecca Elliott: University of Manchester
Tianye Jia: Fudan University
Chao Xie: Fudan University
Shitong Xiang: Fudan University
Nan Wang: Fudan University
Tobias Banaschewski: Heidelberg University
Arun L. W. Bokde: Trinity College Dublin
Sylvane Desrivières: King’s College London
Herta Flor: Heidelberg University
Antoine Grigis: Université Paris-Saclay
Hugh Garavan: University of Vermont
Andreas Heinz: and Berlin Institute of Health
Rüdiger Brühl: Physikalisch-Technische Bundesanstalt (PTB)
Jean-Luc Martinot: CNRS; Centre Borelli
Marie-Laure Paillère Martinot: CNRS; Centre Borelli
Eric Artiges: CNRS; Centre Borelli
Frauke Nees: Heidelberg University
Dimitri Papadopoulos Orfanos: University of Mannheim
Herve Lemaitre: Université Paris-Saclay
Luise Poustka: University Hospital Heidelberg
Sarah Hohmann: Heidelberg University
Nathalie Holz: Heidelberg University
Juliane H. Fröhner: Technische Universität Dresden
Michael N. Smolka: Technische Universität Dresden
Nilakshi Vaidya: Charité University Medicine Berlin
Henrik Walter: and Berlin Institute of Health
Robert Whelan: Trinity College Dublin
Gunter Schumann: Technische Universität Dresden
Jianfeng Feng: University of Warwick
Qiang Luo: Fudan University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-61471-0

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