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独特的生物学特征和可改变的风险因素是重度抑郁症与心血管疾病共病的基础。

Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder and cardiovascular disease.

作者信息

Bergstedt Jacob, Pasman Joëlle A, Ma Ziyan, Harder Arvid, Yao Shuyang, Parker Nadine, Treur Jorien L, Smit Dirk J A, Frei Oleksandr, Shadrin Alexey A, Meijsen Joeri J, Shen Qing, Hägg Sara, Tornvall Per, Buil Alfonso, Werge Thomas, Hjerling-Leffler Jens, Als Thomas D, Børglum Anders D, Lewis Cathryn M, McIntosh Andrew M, Valdimarsdóttir Unnur A, Andreassen Ole A, Sullivan Patrick F, Lu Yi, Fang Fang

机构信息

Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

出版信息

Nat Cardiovasc Res. 2024;3(6):754-769. doi: 10.1038/s44161-024-00488-y. Epub 2024 Jun 17.

DOI:10.1038/s44161-024-00488-y
PMID:38898929
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11182748/
Abstract

Major depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Here we show that CVDs share most of their genetic risk factors with MDD. Multivariate genome-wide association analysis of shared genetic liability between MDD and atherosclerotic CVD revealed seven loci and distinct patterns of tissue and brain cell-type enrichments, suggesting the involvement of the thalamus. Part of the genetic overlap was explained by shared inflammatory, metabolic and psychosocial or lifestyle risk factors. Our data indicated causal effects of genetic liability to MDD on CVD risk, but not from most CVDs to MDD, and showed that the causal effects were partly explained by metabolic and psychosocial or lifestyle factors. The distinct signature of MDD-atherosclerotic CVD comorbidity suggests an immunometabolic subtype of MDD that is more strongly associated with CVD than overall MDD. In summary, we identified biological mechanisms underlying MDD-CVD comorbidity and modifiable risk factors for prevention of CVD in individuals with MDD.

摘要

重度抑郁症（MDD）与心血管疾病（CVD）常常合并存在，导致发病率和死亡率过高。我们在此表明，心血管疾病与重度抑郁症共享其大部分遗传风险因素。对重度抑郁症和动脉粥样硬化性心血管疾病之间共享遗传易感性进行多变量全基因组关联分析，揭示了七个基因座以及不同的组织和脑细胞类型富集模式，提示丘脑参与其中。部分遗传重叠可由共享的炎症、代谢以及心理社会或生活方式风险因素来解释。我们的数据表明，重度抑郁症的遗传易感性对心血管疾病风险具有因果效应，但大多数心血管疾病对重度抑郁症不存在因果效应，并且表明这些因果效应部分可由代谢以及心理社会或生活方式因素来解释。重度抑郁症与动脉粥样硬化性心血管疾病合并症的独特特征表明，存在一种重度抑郁症的免疫代谢亚型，其与心血管疾病的关联比总体重度抑郁症更强。总之，我们确定了重度抑郁症与心血管疾病合并症背后的生物学机制以及可改变的风险因素，以预防重度抑郁症患者发生心血管疾病。

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Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder and cardiovascular disease.独特的生物学特征和可改变的风险因素是重度抑郁症与心血管疾病共病的基础。
Nat Cardiovasc Res. 2024;3(6):754-769. doi: 10.1038/s44161-024-00488-y. Epub 2024 Jun 17.

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