<p>Adolescence is a sensitive period of brain development marked by rapid cortical thinning and increased risk for psychiatric disorders, yet the biological drivers of atypical trajectories remain unclear. Here, using longitudinal data from the Adolescent Brain Cognitive Development Study, we examined whether genetic predisposition to systemic inflammation, indexed by polygenic scores for C-reactive protein (PGS-CRP), influences brain development and psychopathology. Higher PGS-CRP was associated with accelerated cortical thinning, particularly in medial temporal and insular regions, and with increased externalizing symptoms. Early-life infections independently predicted greater depressive and externalizing symptoms but did not interact with genetic risk. Mediation analyses indicated that cortical thinning partially accounted for the association between PGS-CRP and externalizing psychopathology. Biological annotation further identified the regional similarity between cortical effects of PGS-CRP and several neurotransmitter systems. Together, these findings suggest that genetic susceptibility to inflammation may shape adolescent brain maturation and contribute to mental health vulnerability via neuroimmune pathways.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Polygenic score for C-reactive protein is linked to faster cortical thinning and psychopathology risk in adolescents

  • Haixia Zheng,
  • Jonathan Savitz,
  • Ebrahim Haroon,
  • Jonathan Ahern,
  • Robert J. Loughnan,
  • Firas Naber,
  • Bohan Xu,
  • Katherine L. Forthman,
  • Robin L. Aupperle,
  • Leanne M. Williams,
  • Martin P. Paulus,
  • Chun Chieh Fan,
  • Wesley K. Thompson

摘要

Adolescence is a sensitive period of brain development marked by rapid cortical thinning and increased risk for psychiatric disorders, yet the biological drivers of atypical trajectories remain unclear. Here, using longitudinal data from the Adolescent Brain Cognitive Development Study, we examined whether genetic predisposition to systemic inflammation, indexed by polygenic scores for C-reactive protein (PGS-CRP), influences brain development and psychopathology. Higher PGS-CRP was associated with accelerated cortical thinning, particularly in medial temporal and insular regions, and with increased externalizing symptoms. Early-life infections independently predicted greater depressive and externalizing symptoms but did not interact with genetic risk. Mediation analyses indicated that cortical thinning partially accounted for the association between PGS-CRP and externalizing psychopathology. Biological annotation further identified the regional similarity between cortical effects of PGS-CRP and several neurotransmitter systems. Together, these findings suggest that genetic susceptibility to inflammation may shape adolescent brain maturation and contribute to mental health vulnerability via neuroimmune pathways.