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

Transl Psychiatry. 2025 Aug 21;15(1):305. doi: 10.1038/s41398-025-03513-1.

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.

PMID:40841533 | DOI:10.1038/s41398-025-03513-1