Endothelial Function in Youth With Bipolar Disorder: Preliminary Evidence for Mood Polarity Differences

Bipolar disorder (BD) confers risk for accelerated atherosclerosis and early cardiovascular disease (CVD). In adults, mood symptom burden is associated with CVD. Here we examine endothelial dysfunction, considered an early predictor of CVD, in relation to mood states and symptoms among youth with BD.

Participants were 209 youth, aged 13-20 years, including 114 with BD and 95 healthy controls (HC) recruited between 2012 and 2020. Diagnoses and mood symptoms were ascertained using validated, semi-structured interviews based on DSM-IV-TR criteria. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry (PAT). RHI was compared across 4 groups: BD-euthymic (n = 34), BD-depressed (n = 36), BD-hypomanic/mixed (n = 44), and HC (n = 95) controlling for age, sex, and obesity. Analyses also examined for RHI-mood associations in the overall BD group.

RHI was significantly different between groups (F_3,202 = 4.47, P = .005, η_p² = 0.06). Specifically, RHI was lower in the BD-depressed group compared to HC (P = .04, d = 0.4). Additionally, the BD-hypomanic/mixed group had higher RHI compared to the BD-euthymic (P = .02, d = 0.55), BD-depressed (P < .001, d = 0.79), and HC (P = .04, d = 0.55) groups. Lastly, within the BD group, higher RHI was associated with higher mania scores (P = .006, β = 0.26), but not depression scores. All analyses remained significant in sensitivity analyses further controlling for cardiovascular risk factors and for current lithium, second-generation antipsychotic, and any medication use.

We found that symptomatic youth with BD have anomalous RHI, which varies according to mood polarity. Future studies in larger samples, with prospective repeated measures, should investigate whether endothelial dysfunction partially subserves the psychiatric symptoms and cardiovascular risk observed in BD.