Neurobiology of disease · 2026
Higher polygenic risk for cardiovascular disease is associated with lower cerebral blood flow in youth with bipolar disorder.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kulkarni Nidhi P, Zai Clement C, Kennedy Kody G, Mio Megan, Young L Trevor, MacIntosh Bradley J, Goldstein Benjamin I
Аннотация
BACKGROUND: Bipolar disorder (BD) is associated with excess cardiovascular burden and anomalous cerebral blood flow (CBF). We examined coronary artery disease (CAD) and myocardial infarction (MI) polygenic risk scores (PRS) in relation to CBF among youth with BD.
METHODS: Participants (mean age 17.2 years; n = 63 BD, n = 41 healthy controls [HC]) underwent magnetic resonance imaging to quantify CBF using arterial spin labelling. CAD-PRS and MI-PRS were calculated using adult genome-wide association summary statistics. Covariate-adjusted voxel-wise analyses examined associations of CAD-PRS and MI-PRS with CBF in the combined sample, and within subgroups. Sex-stratified analyses and PRS-by-diagnosis interaction effects were also examined. Sensitivity analyses controlled for psychotropic medications, cardiovascular risk factors, and mood.
RESULTS: Higher MI-PRS was associated with lower CBF in one occipital cluster (β = -0.44, p = 0.003) in the combined sample, and two frontal and one occipital cluster within BD (βrange = -0.47 to -0.51, prange = 0.03 to <0.001). Higher CAD-PRS was associated with higher caudal CBF within HC (β = 0.41, p ≤ 0.001; n.s. after controlling for cardiovascular risk factors). PRS-by-diagnosis interactions revealed three significant clusters for MI-PRS (βrange = -0.34 to -0.35, prange = 0.03 to <0.001) and two significant clusters for CAD-PRS (βrange = -0.32 to -0.33, prange = 0.001 to <0.001). In post-hoc analyses, higher PRS was associated with lower CBF within BD and higher CBF within HC.
CONCLUSIONS: Higher polygenic risk for cardiovascular disease was associated with lower regional CBF in youth with BD, convergent with prior findings in adults and divergent from healthy youth in the current study. Future longitudinal studies incorporating putative mediators of the observed findings are warranted.
METHODS: Participants (mean age 17.2 years; n = 63 BD, n = 41 healthy controls [HC]) underwent magnetic resonance imaging to quantify CBF using arterial spin labelling. CAD-PRS and MI-PRS were calculated using adult genome-wide association summary statistics. Covariate-adjusted voxel-wise analyses examined associations of CAD-PRS and MI-PRS with CBF in the combined sample, and within subgroups. Sex-stratified analyses and PRS-by-diagnosis interaction effects were also examined. Sensitivity analyses controlled for psychotropic medications, cardiovascular risk factors, and mood.
RESULTS: Higher MI-PRS was associated with lower CBF in one occipital cluster (β = -0.44, p = 0.003) in the combined sample, and two frontal and one occipital cluster within BD (βrange = -0.47 to -0.51, prange = 0.03 to <0.001). Higher CAD-PRS was associated with higher caudal CBF within HC (β = 0.41, p ≤ 0.001; n.s. after controlling for cardiovascular risk factors). PRS-by-diagnosis interactions revealed three significant clusters for MI-PRS (βrange = -0.34 to -0.35, prange = 0.03 to <0.001) and two significant clusters for CAD-PRS (βrange = -0.32 to -0.33, prange = 0.001 to <0.001). In post-hoc analyses, higher PRS was associated with lower CBF within BD and higher CBF within HC.
CONCLUSIONS: Higher polygenic risk for cardiovascular disease was associated with lower regional CBF in youth with BD, convergent with prior findings in adults and divergent from healthy youth in the current study. Future longitudinal studies incorporating putative mediators of the observed findings are warranted.