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Higher polygenic risk for cardiovascular disease is associated with lower cerebral blood flow in youth with bipolar

Nidhi P Kulkarni1, Clement C Zai2, Kody G Kennedy1

  • 1Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, Canada.

Neurobiology of Disease
|March 10, 2026
PubMed

Insights

Higher polygenic risk for cardiovascular disease is linked to reduced cerebral blood flow (CBF) in adolescents with bipolar disorder (BD). This contrasts with findings in healthy youth, suggesting a unique relationship between genetic cardiovascular risk and brain blood flow in BD.

Area of Science:

  • Neuroscience
  • Genetics
  • Cardiovascular Science

Background:

  • Bipolar disorder (BD) is associated with increased cardiovascular risk and altered cerebral blood flow (CBF).
  • Understanding the interplay between genetic predisposition to cardiovascular disease and brain hemodynamics in youth with BD is crucial.

Purpose of the Study:

  • To investigate the association between polygenic risk scores (PRS) for coronary artery disease (CAD) and myocardial infarction (MI) and regional CBF in adolescents with BD.
  • To explore differences in these associations between individuals with BD and healthy controls (HC).

Main Methods:

  • Magnetic resonance imaging (MRI) with arterial spin labeling (ASL) was used to quantify CBF in 63 youth with BD and 41 HC.
  • Genome-wide association study (GWAS) summary statistics were used to calculate CAD-PRS and MI-PRS.
  • Voxel-wise analyses examined associations between PRS and CBF, controlling for relevant covariates and exploring interaction effects.

Main Results:

  • Higher MI-PRS was associated with lower CBF in occipital and frontal clusters in the combined sample and within the BD group.
  • Higher CAD-PRS was associated with higher CBF in healthy controls, but this effect was not significant after controlling for cardiovascular risk factors.
  • Significant PRS-by-diagnosis interactions indicated differential associations of CAD-PRS and MI-PRS with CBF between BD and HC groups, with higher PRS linked to lower CBF in BD and higher CBF in HC.

Conclusions:

  • Elevated polygenic risk for cardiovascular disease is associated with reduced regional CBF in adolescents with BD.
  • These findings align with adult studies but diverge from observations in healthy youth.
  • Further longitudinal research is needed to elucidate the mechanisms underlying these associations.
Abstract

Keywords:
Bipolar disorderCardiovascular geneticsCerebral perfusionYouth

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