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

TL;DR

This study finds that genetic predisposition to inflammation is linked to faster brain changes and higher risk of mental health issues in adolescents.

Contribution

The study introduces a novel link between polygenic scores for C-reactive protein and adolescent brain development and psychopathology.

Findings

Higher PGS-CRP is associated with accelerated cortical thinning in medial temporal and insular regions.

PGS-CRP is linked to increased externalizing symptoms, partially mediated by cortical thinning.

Cortical effects of PGS-CRP show regional similarity to neurotransmitter systems.

Abstract

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.

This study investigates whether genetic predisposition to systemic inflammation affects cortical thinning trajectories and the risk for psychopathology in adolescents, using data from the Adolescent Brain Cognitive Development Study.

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