Vaccarino Viola, Votaw John, Faber Tracy, Veledar Emir, Murrah Nancy V, Jones Linda R, Zhao Jinying, Su Shaoyong, Goldberg Jack, Raggi J Paolo, Quyyumi Arshed A, Sheps David S, Bremner J Douglas
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30306, USA.
Arch Intern Med. 2009 Oct 12;169(18):1668-76. doi: 10.1001/archinternmed.2009.330.
Major depressive disorder (MDD) is associated with coronary heart disease (CHD), but the mechanisms are unclear. The presence of MDD may increase CHD risk by affecting microvascular circulation. It is also plausible that genetic factors influencing MDD may overlap with those for CHD. We sought to examine the relationship between MDD and coronary flow reserve (CFR), the ratio of maximum flow during stress to flow at rest measured in milliliters per minute per gram of tissue.
We examined 289 male middle-aged twins, including 106 twins (53 twin pairs) discordant for a lifetime history of MDD and 183 control twins (unrelated to any twins in the experimental group) without MDD. To calculate CFR, we used positron emission tomography with nitrogen 13 ((13)N) ammonia to evaluate myocardial blood flow at rest and after adenosine stress. A standard perfusion defect score was also used to assess myocardial ischemia.
There was no difference in myocardial ischemia between twins with and without MDD. Among the dizygotic twin pairs discordant for MDD, the CFR was 14% lower in the twins with MDD than in their brothers without MDD (2.36 vs 2.74) (P = .03). This association was not present in the monozygotic discordant pairs who were genetically matched (2.86 vs 2.64) (P = .19). The zygosity-MDD interaction after adjustment was significant (P = .006). The CFR in the dizygotic twins with MDD was also lower than in the control twins.
Our results provide evidence for a shared genetic pathway between MDD and microvascular dysfunction. Common pathophysiologic processes may link MDD and early atherosclerosis.
重度抑郁症(MDD)与冠心病(CHD)相关,但机制尚不清楚。MDD的存在可能通过影响微血管循环增加CHD风险。影响MDD的遗传因素也可能与影响CHD的遗传因素重叠。我们试图研究MDD与冠状动脉血流储备(CFR)之间的关系,CFR是应激时最大血流与静息血流的比值,以每分钟每克组织的毫升数来衡量。
我们研究了289名男性中年双胞胎,其中包括106对(53对双胞胎)有MDD终生病史的不一致双胞胎,以及183名无MDD的对照双胞胎(与实验组中的任何双胞胎无关)。为了计算CFR,我们使用氮13(¹³N)氨正电子发射断层扫描来评估静息和腺苷应激后的心肌血流。还使用标准灌注缺损评分来评估心肌缺血。
有MDD和无MDD的双胞胎在心肌缺血方面没有差异。在MDD不一致的异卵双胞胎对中,患有MDD的双胞胎的CFR比没有MDD的兄弟低14%(2.36对2.74)(P = 0.03)。这种关联在基因匹配的同卵不一致双胞胎对中不存在(2.86对2.64)(P = 0.19)。调整后的合子性-MDD相互作用具有显著性(P = 0.006)。患有MDD的异卵双胞胎的CFR也低于对照双胞胎。
我们的结果为MDD和微血管功能障碍之间共享的遗传途径提供了证据。共同的病理生理过程可能将MDD和早期动脉粥样硬化联系起来。