A common neural signature between genetic and environmental risk for mental illness

Vedechkina, Maria, Holmes, Joni, Warrier, Varun and Astle, Duncan E. (2025) A common neural signature between genetic and environmental risk for mental illness. Translational Psychiatry, 15 (1). ISSN 2158-3188

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Abstract

Not everyone is equally likely to experience mental illness. What is the contribution of an individual’s genetic background and experiences of childhood adversity to that likelihood? And how do these risk factors interact at the level of the brain? This study explores these questions by investigating the relationship between genetic liability for mental illness, childhood adversity, and cortico-limbic connectivity in a large developmental sample drawn from the ABCD cohort (N = 6535). Canonical Correlation Analysis – a multivariate data-reduction technique – revealed two genetic dimensions of mental illness from the polygenic risk scores for ADHD, Anxiety, Depression, and Psychosis. The first dimension represented liability for broad psychopathology which was positively correlated with adversity. The second dimension represented neurodevelopmental-specific risk which negatively interacted with adversity, suggesting that neurodevelopmental symptoms may arise from unique combinations of genetic and environmental factors that differ from other symptom domains. Next, we investigated the cortico-limbic signature of adversity and genetic liability using Partial Least Squares. We found that the neural correlates of adversity broadly mirrored those of genetic liability, with adversity capturing most of the shared variance. These novel findings suggest that genetic and environmental risk overlap in the neural connections that underlie mental health symptomatology.

Item Type:	Article
Additional Information:	Data availability: The datasets analysed during the current study are available in the NIMH Data Archive (NDA) repository, https://doi.org/10.15154/1523041. Code availability: The underlying code for this study is not publicly available but may be made available to qualified researchers on reasonable request from the corresponding author.
Uncontrolled Keywords:	psychiatry and mental health,cellular and molecular neuroscience,biological psychiatry,sdg 3 - good health and well-being,3* ,/dk/atira/pure/subjectarea/asjc/2700/2738
Faculty \ School:	Faculty of Social Sciences > School of Psychology
UEA Research Groups:	Faculty of Social Sciences > Research Groups > Developmental Science Faculty of Social Sciences > Research Groups > Cognition, Action and Perception
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	02 Mar 2026 16:30
Last Modified:	09 Mar 2026 16:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102140
DOI:	10.1038/s41398-025-03513-1

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