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Background: Abnormalities in cerebral blood flow (CBF) are common in bipolar disorder (BD). Despite known differences in CBF between healthy adolescent males and females, sex differences in CBF among adolescents with BD have never been studied., Objective: To examine sex differences in CBF among adolescents with BD versus healthy controls (HC)., Methods: CBF images were acquired using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in 123 adolescents (72 BD: 30M, 42F; 51 HC: 22M, 29F) matched for age (13-20 years). Whole brain voxel-wise analysis was performed in a general linear model with sex and diagnosis as fixed factors, sex-diagnosis interaction effect, and age as a covariate. We tested for main effects of sex, diagnosis, and their interaction. Results were thresholded at cluster forming p = 0.0125, with posthoc Bonferroni correction (p = 0.05/4 groups)., Results: A main effect of diagnosis (BD > HC) was observed in the superior longitudinal fasciculus (SLF), underlying the left precentral gyrus (F =10.24 (3), p < 0.0001). A main effect of sex (F > M) on CBF was detected in the precuneus/posterior cingulate cortex (PCC), left frontal and occipital poles, left thalamus, left SLF, and right inferior longitudinal fasciculus (ILF). No regions demonstrated a significant sex-by-diagnosis interaction. Exploratory pairwise testing in regions with a main effect of sex revealed greater CBF in females with BD versus HC in the precuneus/PCC (F = 7.1 (3), p < 0.01)., Conclusion: Greater CBF in female adolescents with BD versus HC in the precuneus/PCC may reflect the role of this region in the neurobiological sex differences of adolescent-onset BD. Larger studies targeting underlying mechanisms, such as mitochondrial dysfunction or oxidative stress, are warranted., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Background: Mood symptoms and disorders are associated with impaired endothelial function, a marker of early atherosclerosis. Given the increased vascular burden and neurostructural differences among individuals with mood disorders, we investigated the endothelial function and brain structure interface in relation to youth bipolar disorder (BD)., Methods: This cross-sectional case-controlled study included 115 youth, ages 13-20 years (n = 66 BD; n = 49 controls [CG]). Cortical thickness and volume for regions of interest (ROI; insular cortex, ventrolateral prefrontal cortex [vlPFC], temporal lobe) were acquired from FreeSurfer processed T1-weighted MRI images. Endothelial function was assessed using pulse amplitude tonometry, yielding a reactive hyperemia index (RHI). ROI and vertex-wise analyses controlling for age, sex, obesity, and intracranial volume investigated for RHI-neurostructural associations, and RHI-by-diagnosis interactions., Results: In ROI analyses, higher RHI (i.e., better endothelial function) was associated with lower thickness in the insular cortex (β = -0.19, p FDR  = 0.03), vlPFC (β = -0.30, p FDR  = 0.003), and temporal lobe (β = -0.22, p FDR  = 0.01); and lower temporal lobe volume (β = -0.16, p FDR  = 0.01) in the overall sample. In vertex-wise analyses, higher RHI was associated with lower cortical thickness and volume in the insular cortex, prefrontal cortex (e.g., vlPFC), and temporal lobe. Additionally, higher RHI was associated with lower vlPFC and temporal lobe volume to a greater extent in youth with BD vs. CG., Conclusions: Better endothelial function was associated with lower regional brain thickness and volume, contrasting the hypothesized associations. Additionally, we found evidence that this pattern was exaggerated in youth with BD. Future studies examining the direction of the observed associations and underlying mechanisms are warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)