Mitchell Rachel H B, Grigorian Anahit, Robertson Andrew, Toma Simina, Luciw Nicholas J, Karthikeyan Sudhir, Mutsaerts Henri J M M, Fiksenbaum Lisa, Metcalfe Arron W S, MacIntosh Bradley J, Goldstein Benjamin I
Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Bipolar Disord. 2024 Feb;26(1):33-43. doi: 10.1111/bdi.13326. Epub 2023 May 22.
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.
To examine sex differences in CBF among adolescents with BD versus healthy controls (HC).
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).
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).
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.
脑血流（CBF）异常在双相情感障碍（BD）中很常见。尽管已知健康青少年男性和女性之间的CBF存在差异，但从未对BD青少年的CBF性别差异进行过研究。
研究BD青少年与健康对照（HC）之间的CBF性别差异。
使用动脉自旋标记（ASL）灌注磁共振成像（MRI）对123名年龄匹配（13 - 20岁）的青少年进行CBF图像采集（72名BD患者：30名男性，42名女性；51名HC：22名男性，29名女性）。在一个通用线性模型中进行全脑体素分析，将性别和诊断作为固定因素，性别 - 诊断交互效应，并将年龄作为协变量。我们测试了性别、诊断及其交互作用的主要效应。结果在聚类形成p = 0.0125时进行阈值设定，并进行事后Bonferroni校正（p = 0.05 / 4组）。
在左侧中央前回下方的上纵束（SLF）中观察到诊断的主要效应（BD > HC）（F = 10.24（3），p < 0.0001）。在楔前叶/后扣带回皮质（PCC）、左侧额极和枕极、左侧丘脑、左侧SLF和右侧下纵束（ILF）中检测到性别对CBF的主要效应（女性>男性）。没有区域显示出显著的性别×诊断交互作用。在具有性别主要效应的区域进行探索性成对测试发现，与HC相比，BD女性在楔前叶/PCC中的CBF更高（F = 7.1（3），p < 0.01）。
与HC相比，BD女性青少年在楔前叶/PCC中的CBF更高，这可能反映了该区域在青少年起病BD的神经生物学性别差异中的作用。有必要针对潜在机制进行更大规模的研究，如线粒体功能障碍或氧化应激。
