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Genetic risk-dependent brain markers of resilience to childhood Trauma

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Title: Genetic risk-dependent brain markers of resilience to childhood Trauma
Authors: Lu, Han, Rolls, Edmund T, Liu, Hanjia, Stein, Dan J, Sahakian, Barbara J, Elliott, Rebecca, Jia, Tianye, Xie, Chao, Xiang, Shitong, Wang, Nan, Banaschewski, Tobias, Bokde, Arun LW, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Heinz, Andreas, Brühl, Rüdiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Lemaitre, Herve, Poustka, Luise, Hohmann, Sarah, Holz, Nathalie, Fröhner, Juliane H, Smolka, Michael N, Vaidya, Nilakshi, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Feng, Jianfeng, Luo, Qiang, IMAGEN Consortium
Contributors: Apollo - University of Cambridge Repository
Source: Nat Commun
Publisher Information: Springer Science and Business Media LLC, 2025.
Publication Year: 2025
Subject Terms: Male, Adolescent, Resilience, Depression, Adverse Childhood Experiences/psychology, Brain, Prefrontal Cortex, Depression/genetics, Resilience, Psychological, Brain/diagnostic imaging, Magnetic Resonance Imaging, Article, Young Adult, Adverse Childhood Experiences, Risk Factors, Humans, Psychological, Prefrontal Cortex/diagnostic imaging, Female, Genetic Predisposition to Disease, Longitudinal Studies, Prospective Studies, Child, Biomarkers
Description: 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.
Document Type: Article
Other literature type
File Description: application/pdf; text/xml; application/zip
Language: English
ISSN: 2041-1723
DOI: 10.1038/s41467-025-61471-0
Access URL: https://research.manchester.ac.uk/en/publications/ec053734-8267-4d52-b6d3-68ae51890fb9
https://doi.org/10.1038/s41467-025-61471-0
Rights: CC BY NC ND
Accession Number: edsair.doi.dedup.....d32628158f3110e981806e210f820dc0
Database: OpenAIRE
Description
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.
ISSN:20411723
DOI:10.1038/s41467-025-61471-0