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基于人群的队列研究及体外肝脂肪生成相关基因表达研究抗抑郁药对抑郁症患者发生高脂血症风险的影响。

Influences of antidepressant medications on the risk of developing hyperlipidemia in patients with depression by a population-based cohort study and on in vitro hepatic lipogenic-related gene expression.

机构信息

Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.

Department of Pharmacy, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, Taiwan.

出版信息

J Affect Disord. 2021 Dec 1;295:271-283. doi: 10.1016/j.jad.2021.08.041. Epub 2021 Aug 26.

Abstract

BACKGROUND

Depression increases the risk of cardiovascular disease (CVD). The association between antidepressant medications (ADMs) and CVD remains controversial. Hyperlipidemia is a risk factor for CVD. We conducted a nationwide population-based retrospective cohort study to examine depression and ADM use on the risk of developing hyperlipidemia. The effects of ADMs on the expression of lipogenesis-related hepatic genes were also evaluated.

METHODS

We obtained data from the Longitudinal Health Insurance Database of Taiwan on patients with new-onset depression and a comparison cohort without depression. A Cox proportional hazards regression model was used to analyze the differences in the risk of developing hyperlipidemia between these two cohorts. We also examined the influence of ADMs on the expression of lipogenesis-related hepatic genes.

RESULTS

After adjustment for comorbidities and confounding factors, the case group (N = 38,322) had a higher risk for hyperlipidemia than that of the control cohort (N = 38,322) [adjusted hazards ratio (aHR) =1.16]. Patients with depression who did not receive ADM therapy exhibited a significantly higher risk of hyperlipidemia (aHR = 1.61). However, in patients with depression treated with ADMs, the risk of developing hyperlipidemia was significantly lowered compared to the patients without ADMs (all aHR < 0.81). Gene expression analysis indicated that ADMs downregulated the expression of lipogenesis-related hepatic genes.

LIMITATIONS

Unmeasured confounding risk factors for hyperlipidemia might not have been included in the study.

CONCLUSIONS

ADMs reduced hyperlipidemia risk in patients with depression, partly by downregulating the expression of lipogenesis-related genes and improving the patients' lipid profiles. Early diagnosis and management of hyperlipidemia would further facilitate the prevention of CVD.

摘要

背景

抑郁症会增加心血管疾病(CVD)的风险。抗抑郁药物(ADM)与 CVD 之间的关联仍存在争议。高血脂是 CVD 的一个风险因素。我们进行了一项全国性基于人群的回顾性队列研究,以检查抑郁症和 ADM 使用与发生高血脂的风险之间的关系。还评估了 ADM 对脂生成相关肝基因表达的影响。

方法

我们从台湾的长期健康保险数据库中获取了新发抑郁症患者和无抑郁症对照队列的数据。使用 Cox 比例风险回归模型分析了这两个队列发生高血脂的风险差异。我们还检查了 ADM 对脂生成相关肝基因表达的影响。

结果

调整合并症和混杂因素后,病例组(N=38322)发生高血脂的风险高于对照组(N=38322)[调整后的风险比(aHR)=1.16]。未接受 ADM 治疗的抑郁症患者发生高血脂的风险显著升高(aHR=1.61)。然而,在接受 ADM 治疗的抑郁症患者中,发生高血脂的风险明显低于未接受 ADM 治疗的患者(所有 aHR<0.81)。基因表达分析表明,ADM 下调了脂生成相关肝基因的表达。

局限性

本研究可能未包括高血脂的未测量混杂风险因素。

结论

ADM 降低了抑郁症患者的高血脂风险,部分原因是下调了脂生成相关基因的表达并改善了患者的血脂谱。早期诊断和管理高血脂将进一步促进 CVD 的预防。

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