Genetic and striatal structural connection linking behavioral inhibition/activation system to adolescent anxiety and depression.

The Behavioral Inhibition and Activation Systems (BIS/BAS) are central to emotional regulation, yet their genetic and neural mechanisms remain unclear. In this study, we examined how polygenic risk for BIS/BAS relates to striatal structural connectivity and emotional vulnerability during adolescence-a critical period for affective problems onset. Using data from 1,929 adolescents (average age 9.95 years, 50.39% female) in the ABCD Study, we found that BIS and BAS polygenic risks exerted dissociable influences on striatal structural gradient (SSG), delineating distinct neurobiological pathways to anxiety and depression. Elevated BIS risk was linked to greater anxiety symptoms, whereas increased BAS risk related more strongly to depressive and withdrawn features. Altogether, our findings elucidate a neuroanatomical pleiotropy mechanism, whereby shared striatal connectivity architectures differentially channel genetic susceptibilities into distinct symptom dimensions, thereby advancing our understanding of the neural pathways underlying emotional vulnerability across diverse psychiatric phenotypes. (a) Construction of PRS. Variants associated with BIS and BAS were extracted from GWAS data. Effect weights were calculated, and a weighted sum was performed to derive the PRS scores, with detailed procedures outlined in the Methods section. (b) Framework for striatal structural connectopic mapping. Probabilistic tractography was conducted from the striatal volumetric seed region. The resulting connectivity matrix, denoted as A, was subjected to dimensionality reduction using Singular Value Decomposition (SVD), resulting in matrix B. Subsequently, the similarity matrix S was computed utilizing the η² Coefficient. The graph's Laplacian was then decomposed into its eigenvectors, which correspond to the connectopic maps of the seed region. (c) Simplified Schematic of a Multivariate Model Investigating Gene-Brain-Behavior Correlations. Green arrows indicate mediation pathways involving BIS PRS. Orange dashed arrows indicate mediation pathways involving BAS PRS. Grey arrows denote significant associations between variables without mediation. GWAS, Genome-Wide Association Study. PRS, Polygenic Risk Scores. BIS, Behavioral Inhibition System. BAS, Behavioral Activation System. BAS_rr, BAS Reward Responsiveness.