Baranova Ancha, Liu Dongming, Sun Wenxi, Xu Chenxin, Chen Miao, Cao Hongbao, Zhang Fuquan
School of Systems Biology, George Mason University, Manassas, Virginia, USA; Research Centre for Medical Genetics, Moscow, Russia.
Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Institute of Medical Imaging and Artificial Intelligence, Nanjing University, Nanjing 210008, China; Department of Neurosurgery, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111164. doi: 10.1016/j.pnpbp.2024.111164. Epub 2024 Oct 5.
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.
This study aimed to investigate the overall and independent effects of MDD and exposure to antidepressants on T2D risk.
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.
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.
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.
重度抑郁症（MDD）患者患2型糖尿病（T2D）的风险升高。然而，疾病本身与抗抑郁药的副作用对这种风险增加的贡献仍不清楚。
本研究旨在调查MDD和接触抗抑郁药对T2D风险的总体和独立影响。
汇总全基因组关联研究数据集用于孟德尔随机化（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）的数据集。采用贝叶斯共定位分析揭示MDD、抗抑郁药和T2D之间共享的遗传变异。
我们发现MDD（比值比：1.15，置信区间：1.03 - 1.30，P = 0.016）和抗抑郁药（比值比：1.37，置信区间：1.22 - 1.53，P = 2.75×10⁻⁸）对T2D均有总体因果效应。虽然T2D与使用抗抑郁药的风险相关（比值比：1.08，置信区间：1.06 - 1.11，P = 8.80×10⁻¹⁰），但与MDD的风险无关（比值比：1.00，置信区间：0.98 - 1.01，P = 0.661）。我们的MVMR分析表明，使用抗抑郁药与T2D的较高风险相关（比值比：1.21，置信区间：1.07 - 1.37，P = 7.19×10⁻⁴），而MDD与T2D的风险无关（比值比：1.01，置信区间：0.86 - 1.18，P = 0.799）。共定位分析确定了抗抑郁药和T2D之间的两个共享基因座。
MDD患者T2D风险升高主要是由使用抗抑郁药引起的。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。
