Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Physical Sciences, Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Physics and Computational Radiology, Oslo University Hospital, Oslo, Norway.
Prog Neuropsychopharmacol Biol Psychiatry. 2024 Dec 20;135:111087. doi: 10.1016/j.pnpbp.2024.111087. Epub 2024 Jul 14.
Anomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD.
Participants included 113 youth, 13-20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses.
ROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (p < 0.001). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (p < 0.001), left thalamus (p < 0.001), and right frontal pole (p = 0.006). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC.
We found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.
在双相情感障碍（BD）中，异常的脑血流（CBF）是显而易见的，但 CBF 反映 BD 患者外周血管功能的程度尚不清楚。本研究旨在探讨青年 BD 患者的脑血流与内皮功能（动脉粥样硬化和心血管疾病风险的早期指标）之间的关系。
参与者包括 113 名年龄在 13-20 岁的青少年（66 名 BD；47 名健康对照组 [HC]）。使用 3T MRI 的动脉自旋标记法测量 CBF。进行了感兴趣区分析（ROI；全脑灰质、额中回、前扣带回皮质、颞叶皮质、尾状核）以及体素分析。通过脉搏幅度张力测定无创地评估反应性充血指数（RHI），以评估内皮功能。采用一般线性模型，在控制年龄、性别和体重指数的情况下，检查 RHI 和 RHI-诊断与 CBF 的关联。对 ROI 分析采用 Bonferroni 校正进行多重比较，即将显著性水平除以 ROI 的数量（α=0.05/5=0.01）。对体素分析采用簇扩展阈值校正进行多重比较校正。
校正后 ROI 结果不显著。体素分析发现，全组中较高的 RHI 与左丘脑 CBF 较低有关（p<0.001）。此外，还发现了与 CBF 存在显著 RHI-诊断关联的三个簇：左内囊皮层（p<0.001）、左丘脑（p<0.001）和右额极（p=0.006）。事后分析显示，在每个簇中，较高的 RHI 与 BD 中 CBF 较低有关，但在 HC 中 CBF 较高。
我们发现，RHI 与 BD 和 HC 青少年的 CBF 有不同的关联。BD 中较高的 RHI 与较低的 CBF 之间的意外关联可能反映了一种代偿机制。需要进行包括前瞻性研究和实验设计在内的进一步研究，以进一步阐明当前的研究结果。
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