Higher polygenic scores for C-reactive protein is associated with lower striatal reward magnitude coding in early adolescents

Higher polygenic scores for C-reactive protein is associated with lower striatal reward magnitude coding in early adolescents

Heritage LA, Chat IK, Ahern J, Loughnan RJ, Aupperle RL, Fan CC, Paulus MP, Thompson WK, Zheng H

PMID: 42633819

Abstract

Low-grade inflammation has been linked to altered reward processing and risk for mood disorders in adults, yet it remains unclear whether genetic liability for inflammation is associated with reward circuitry function before the typical age of onset for depression and anhedonia. Using data from the Adolescent Brain and Cognitive Development Study, we examined whether a polygenic score for C-reactive protein (PGS-CRP) was associated with striatal activation during reward processing in 4,830 children of European ancestry (ages 9-10). Participants com pleted the Monetary Incentive Delay task during functional MRI. Linear mixed-effects models tested associations between high versus low PGS-CRP and activation in the nucleus accumbens, caudate, and putamen during reward and loss anticipation and feedback, adjusting for sociodemographic, anthropometric, scanner, and genetic ancestry covariates. Higher PGS-CRP was associated with attenuated activation across all three striatal regions (i.e., the nucleus accumbens, caudate, and putamen) during anticipation of large relative to small rewards at baseline (all p <&nbsp;0.05, beta coefficient range from -0.014 to -0.017). Associations were not observed for loss anticipation, average reward anticipation, or reward/loss feedback, suggesting altered reward-magnitude coding rather than generalized incentive hypoactivation. The caudate effect persisted across 6 years of longitudinal follow-up into mid-to-late adolescence and remained robust after adjustment for psychiatric diagnoses and psychotropic medication. These findings provide the earliest population-level evidence that genetic inflammatory liability is associated with attenuated striatal reward-value coding, identifying a candidate neuroimmune pathway preceding clinical risk.

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