Department of Psychiatry and Neuropsychology (A.F.J.G., S.K., M.T.S.), Maastricht University Medical Center (MUMC+), the Netherlands.
Department of Internal Medicine (A.F.J.G., M.J.M.v.A., C.D.A.S., B.M.S., N.C.S., R.M.A.H., C.J.H.v.d.K., T.T.v.S., M.T.S., A.J.H.M.H.), Maastricht University Medical Center (MUMC+), the Netherlands.
Hypertension. 2020 Aug;76(2):342-349. doi: 10.1161/HYPERTENSIONAHA.120.15260. Epub 2020 Jul 8.
The etiology of late-life depression (LLD) is still poorly understood. Microvascular dysfunction (MVD) has been suggested to play a role in the etiology of LLD, but direct evidence of this association is scarce. The aim of this study was to investigate whether direct and indirect markers of early microvascular dysfunction are associated with prevalent and incident LLD in the population-based Maastricht Study cohort. We measured microvascular dysfunction at baseline by use of flicker light-induced retinal vessel dilation response (Dynamic Vessel Analyzer), heat-induced skin hyperemic response (laser- Doppler flowmetry), and plasma markers of endothelial dysfunction (endothelial dysfunction; sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [Von Willebrand Factor]). Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) at baseline and annually over 4 years of follow-up (n=3029; mean age 59.6±8.2 years, 49.5% were women, n=132 and n=251 with prevalent and incident depressive symptoms [PHQ-9≥10]). We used logistic, negative binominal and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle factors. Retinal venular dilatation and plasma markers of endothelial dysfunction were associated with the more prevalent depressive symptoms after full adjustment (PHQ-9 score, RR, 1.05 [1.00-1.11] and RR 1.06 [1.01-1.11], respectively). Retinal venular dilatation was also associated with prevalent depressive symptoms (PHQ-9≥10; odds ratio, 1.42 [1.09-1.84]), after full adjustment. Retinal arteriolar dilatation and plasma markers of endothelial dysfunction were associated with incident depressive symptoms (PHQ-9≥10; HR, 1.23 [1.04-1.46] and HR, 1.19 [1.05-1.35]), after full adjustment. These findings support the concept that microvascular dysfunction in the retina, and plasma markers of endothelial dysfunction is involved in the etiology of LLD and might help in finding additional targets for the prevention and treatment of LLD.
老年期抑郁症（LLD）的病因仍知之甚少。微血管功能障碍（MVD）被认为在 LLD 的病因中起作用，但这种关联的直接证据很少。本研究旨在调查人群中直接和间接的早期微血管功能障碍标志物是否与普遍和新发的 LLD 相关。我们使用闪烁光诱导的视网膜血管扩张反应（动态血管分析仪）、热诱导的皮肤充血反应（激光多普勒血流计）和内皮功能障碍的血浆标志物（内皮功能障碍；可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）、可溶性 E 选择素（sE-selectin）和血管性血友病因子（vWF））在基线时测量微血管功能障碍。使用 9 项患者健康问卷（PHQ-9）在基线和 4 年的随访期间每年评估抑郁症状（n=3029；平均年龄 59.6±8.2 岁，49.5%为女性，n=132 和 n=251 为有或无抑郁症状[PHQ-9≥10]）。我们使用逻辑、负二项式和 Cox 回归分析，并调整了人口统计学、心血管和生活方式因素。视网膜静脉扩张和内皮功能障碍的血浆标志物与调整后更普遍的抑郁症状相关（PHQ-9 评分，RR，1.05[1.00-1.11]和 RR 1.06[1.01-1.11]）。视网膜静脉扩张也与普遍的抑郁症状相关（PHQ-9≥10；优势比，1.42[1.09-1.84]），经全面调整后。视网膜小动脉扩张和内皮功能障碍的血浆标志物与新发抑郁症状相关（PHQ-9≥10；HR，1.23[1.04-1.46]和 HR，1.19[1.05-1.35]），经全面调整后。这些发现支持微血管功能障碍在视网膜中，以及内皮功能障碍的血浆标志物与 LLD 的病因有关的概念，并且可能有助于寻找预防和治疗 LLD 的其他靶点。
