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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Cardiovascular Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1411343

The causal relationship between antihypertensive drugs and depression: A Mendelian randomization study of drug targets

Provisionally accepted
Zixian Yang Zixian Yang 1,2Jinshuai Li Jinshuai Li 3*Peichu Huang Peichu Huang 2,4*Zhichang Li Zhichang Li 4*Jianfeng He Jianfeng He 2,4*Dongchun Cai Dongchun Cai 2,4*Yuzheng Lai Yuzheng Lai 2,4*
  • 1 School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
  • 2 Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, China
  • 3 The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China
  • 4 Foshan Nanhai District People's Hospital, Foshan, China

The final, formatted version of the article will be published soon.

    Background: Depression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensive medications and depression has garnered significant interest. Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensive medications on depression by conducting a Mendelian randomization study focused on drug targets. Method: We focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression. Results: Our findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p < 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk. Conclusion: The study suggests that genetic proxies associated with Beta-Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals.

    Keywords: antihypertensive drugs, Depression, Mendelian randomization, beta-blockers, Calcium Channel Blockers

    Received: 02 Apr 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Yang, Li, Huang, Li, He, Cai and Lai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jinshuai Li, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China
    Peichu Huang, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, China
    Zhichang Li, Foshan Nanhai District People's Hospital, Foshan, China
    Jianfeng He, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, China
    Dongchun Cai, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, China
    Yuzheng Lai, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.