TY - JOUR
T1 - Genetic risk-dependent brain markers of resilience to childhood Trauma
AU - IMAGEN Consortium
AU - Lu, Han
AU - Rolls, Edmund T
AU - Liu, Hanjia
AU - Stein, Dan J
AU - Sahakian, Barbara J
AU - Elliott, Rebecca
AU - Jia, Tianye
AU - Xie, Chao
AU - Xiang, Shitong
AU - Wang, Nan
AU - Banaschewski, Tobias
AU - Bokde, Arun L W
AU - Desrivières, Sylvane
AU - Flor, Herta
AU - Grigis, Antoine
AU - Garavan, Hugh
AU - Heinz, Andreas
AU - Brühl, Rüdiger
AU - Martinot, Jean-Luc
AU - Martinot, Marie-Laure Paillère
AU - Artiges, Eric
AU - Nees, Frauke
AU - Orfanos, Dimitri Papadopoulos
AU - Lemaitre, Herve
AU - Poustka, Luise
AU - Hohmann, Sarah
AU - Holz, Nathalie
AU - Fröhner, Juliane H
AU - Smolka, Michael N
AU - Vaidya, Nilakshi
AU - Walter, Henrik
AU - Whelan, Robert
AU - Schumann, Gunter
AU - Feng, Jianfeng
AU - Luo, Qiang
N1 - © 2025. The Author(s).
PY - 2025/7/5
Y1 - 2025/7/5
N2 - 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.
AB - 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.
KW - Humans
KW - Female
KW - Adolescent
KW - Resilience, Psychological
KW - Brain/diagnostic imaging
KW - Male
KW - Young Adult
KW - Adverse Childhood Experiences/psychology
KW - Depression/genetics
KW - Genetic Predisposition to Disease
KW - Magnetic Resonance Imaging
KW - Longitudinal Studies
KW - Prospective Studies
KW - Child
KW - Prefrontal Cortex/diagnostic imaging
KW - Risk Factors
KW - Biomarkers
UR - https://www.scopus.com/pages/publications/105010661736
U2 - 10.1038/s41467-025-61471-0
DO - 10.1038/s41467-025-61471-0
M3 - Article
C2 - 40617820
SN - 2041-1723
VL - 16
SP - 6219
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -