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

作者：Jing Lou, Xiaohan Tian, Yuqing Sun, Junxing Xian, Wenkun Lei, Meng Wang, Bing Liu · 发表于：Translational Psychiatry · 年份：2025 · DOI：10.1038/s41398-025-03687-8 · 被引用次数：1 · 研究领域：Functional Brain Connectivity Studies、Mental Health Research Topics、Neural and Behavioral Psychology Studies

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BIS risk was linked to greater anxiety symptoms, whereas increased BAS risk related more strongly to depressive and withdrawn features.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...