Cerebral blood flow in relation to peripheral endothelial function in youth bipolar disorder
Alysha A Sultan1, Sudhir Karthikeyan1, Anahit Grigorian1
1Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Insights
Endothelial function (RHI) was differentially associated with cerebral blood flow (CBF) in youth with bipolar disorder (BD). Higher RHI correlated with lower CBF in BD, potentially indicating a compensatory mechanism in this population.
Area of Science:
- Neuroscience
- Cardiovascular Science
- Psychiatry
Background:
- Anomalous cerebral blood flow (CBF) is observed in bipolar disorder (BD).
- The relationship between peripheral vascular function and CBF in youth with BD is not well understood.
- Endothelial function, a marker of early atherosclerosis and cardiovascular risk, was investigated in relation to CBF.
Purpose of the Study:
- To investigate the association between endothelial function (Reactive Hyperemia Index, RHI) and cerebral blood flow (CBF) in adolescents and young adults with bipolar disorder (BD).
- To determine if peripheral vascular health, as measured by RHI, relates to brain perfusion in youth with BD.
Main Methods:
- 113 participants (66 with BD, 47 healthy controls [HC]), aged 13-20 years.
- Cerebral blood flow (CBF) measured using 3T MRI with arterial spin labeling.
- Endothelial function assessed via Reactive Hyperemia Index (RHI) using pulse amplitude tonometry.
- Statistical analyses included general linear models and voxel-wise analyses, controlling for covariates and applying corrections for multiple comparisons.
Main Results:
- Region of interest analyses did not yield significant results after correction.
- Voxel-wise analyses revealed a significant association between higher RHI and lower left thalamus CBF in the overall group.
- Significant interactions between RHI and diagnosis were found in the left intracalcarine cortex, left thalamus, and right frontal pole, with higher RHI associated with lower CBF in BD but higher CBF in HC.
Conclusions:
- Endothelial function (RHI) shows a differential association with CBF in youth with BD compared to healthy controls (HC).
- The finding of higher RHI correlating with lower CBF in BD may suggest a compensatory mechanism.
- Further research, including prospective and experimental studies, is needed to elucidate these findings.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
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