抗抑郁药是重度抑郁症对 2 型糖尿病的因果效应。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2024-10-05 DOI:10.1016/j.pnpbp.2024.111164

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引用次数: 0

摘要

背景：重度抑郁障碍（MDD）患者罹患 2 型糖尿病（T2D）的风险较高。然而，疾病本身与抗抑郁药副作用对这一风险增加的影响仍不清楚：本研究旨在调查MDD和抗抑郁药暴露对T2D风险的总体和独立影响：方法：利用全基因组关联研究数据集摘要进行孟德尔随机化（MR）和多变量MR（MVMR）分析，包括MDD（N = 500,199）、抗抑郁药（N = 175,161）和T2D（N = 933,970）。贝叶斯共定位分析用于揭示 MDD、抗抑郁药和 T2D 之间的共同遗传变异：结果：我们发现 MDD（OR：1.15，CI：1.03-1.30，P=0.016）和抗抑郁药（OR：1.37，CI：1.22-1.53，P=2.75E-08）对 T2D 都有整体的因果效应。虽然 T2D 与使用抗抑郁药的风险有关（OR：1.08，CI：1.06-1.11，P = 8.80E-10），但与 MDD 的风险无关（OR：1.00，CI：0.98-1.01，P = 0.661）。我们的 MVMR 分析显示，使用抗抑郁药与较高的 T2D 风险相关（OR：1.21，CI：1.07-1.37，P = 7.19E-04），而 MDD 与 T2D 风险无关（OR：1.01，CI：0.86-1.18，P = 0.799）。共定位分析确定了抗抑郁药与T2D之间的两个共享遗传位点：结论：MDD 患者的 T2D 风险升高主要是由服用抗抑郁药引起的。这些发现强调了考虑抗抑郁药对 MDD 患者代谢健康影响的重要性。

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Antidepressants account for the causal effect of major depressive disorder on type 2 diabetes

Background

Patients with major depressive disorder (MDD) face an elevated risk of type 2 diabetes (T2D). However, the contribution of the disease itself versus the side effects of antidepressants to this increased risk remains unclear.

Objective

This study aimed to investigate the overall and independent effects of MDD and exposure to antidepressants on T2D risk.

Methods

Summary genome-wide association study datasets were utilized for the Mendelian randomization (MR) and multivariable MR (MVMR) analyses, including ones for MDD (N = 500,199), antidepressants (N = 175,161), and T2D (N = 933,970). Bayesian colocalization analysis was used to reveal shared genetic variation between MDD, antidepressants, and T2D.

Results

We found that both MDD (OR: 1.15, CI: 1.03–1.30, P = 0.016) and antidepressants (OR: 1.37, CI: 1.22–1.53, P = 2.75E-08) have overall causal effects on T2D. While T2D was associated with the risk of antidepressant use (OR: 1.08, CI: 1.06–1.11, P = 8.80E-10), but not with the risk of MDD (OR: 1.00, CI: 0.98–1.01, P = 0.661). Our MVMR analysis showed that the use of antidepressants is associated with higher risks of T2D (OR: 1.21, CI: 1.07–1.37, P = 7.19E-04), while MDD is not linked to the risk of T2D (OR: 1.01, CI: 0.86–1.18, P = 0.799). Colocalization analysis identified two shared genetic loci between antidepressants and T2D.

Conclusions

The elevated T2D risk in MDD patients is chiefly caused by antidepressant use. These findings emphasize the importance of considering the impact of antidepressants on metabolic health in individuals with MDD.

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来源期刊

Progress in Neuro-Psychopharmacology & Biological Psychiatry 医学-精神病学

CiteScore

12.00

自引率

1.80%

发文量

153

审稿时长

56 days

期刊介绍： Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.