Family environment modulates linkage of transdiagnostic psychiatric phenotypes and dissociable brain features in the developing brain

Background Family environment has long been known for shaping brain function and psychiatric phenotypes, especially in childhood and adolescence. Accumulating neuroimaging evidence suggests that across different psychiatric disorders, common phenotypes might share common neural bases, indicating latent brain–behavior relationships beyond diagnostic categories. However, the influence of family environment on the brain–behavior relationship from a transdiagnostic perspective remains unknown. Method We included a community-based sample of 699 subjects (5–22 yrs.) and applied partial least squares regression analysis to determine latent brain–behavior relationships from the whole brain functional connectivity and comprehensive phenotypic measures. Comparisons were conducted between diagnostic and non–diagnostic groups to help interpret the latent brain–behavior relationships. A moderation model was introduced to examine the potential moderating role of family factors in the estimated brain–behavior association. Results Four significant latent brain–behavior pairs reflecting relationship of dissociable brain network and general behavioral problems, cognitive and language skills, externalizing problems, and social dysfunction, respectively, were identified. The group comparisons exhibited interpretable variations across different diagnostic groups. Warmth family environment was found to moderate the brain–behavior relationship of core symptoms in internalizing disorders. However, in neurodevelopmental disorders, family factors were not found to moderate the brain–behavior relationship of core symptoms, but were found to affect brain–behavior relationship in other domains. Conclusion Our findings leveraged the transdiagnostic analysis investigating the moderating effects of the family factors on brain–behavior association, emphasizing the different role family factors take in developmental period across distinct diagnostic groups.