Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Nov 19, 2023; 13(11): 929-936
Published online Nov 19, 2023. doi: 10.5498/wjp.v13.i11.929
Depression and sarcopenia-related traits: A Mendelian randomization study
Ding-Kun Wang, Yi-Hao Li, Xiao-Ming Guo
Ding-Kun Wang, Yi-Hao Li, Department of Neurosurgery, Tongde Hospital of Zhejiang Province, Hangzhou 310016, Zhejiang Province, China
Xiao-Ming Guo, Department of Neurosurgery, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310012, Zhejiang Province, China
Author contributions: Wang DK and Li YH drafted the initial manuscript, analyzed the data, and interpreted the results; Guo XM designed the study, analyzed the data, and critically revised the manuscript; All authors read and approved the final manuscript.
Supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Project, No. 2023ZR075.
Institutional review board statement: This study only adopted publicly available data. Ethical review and approval were not required for this study in accordance with the local legislation and institutional requirements.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose. They confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Data sharing statement: This study only used publicly available data. Technical appendix, statistical code, and dataset available from the corresponding author at 21718274@zju.edu.cn.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Ming Guo, MD, Doctor, Department of Neurosurgery, Second Affiliated Hospital of Zhejiang University, School of Medicine, No. 88 Jiefang Road, Hangzhou 310012, Zhejiang Province, China. 21718274@zju.edu.cn
Received: August 19, 2023
Peer-review started: August 19, 2023
First decision: September 19, 2023
Revised: October 6, 2023
Accepted: October 23, 2023
Article in press: October 23, 2023
Published online: November 19, 2023

Observational studies have suggested that depression is associated with sarcopenia. However, the causal relationship between depression and sarcopenia remains unclear.


To investigate the causal relationship between depression and sarcopenia.


We performed a Mendelian randomization (MR) analysis to identify the bidirectional relationship between depression and sarcopenia-related traits. Summary-level data and independent variants used as instrumental variables came from large genome-wide association studies of depression (414055 cases and 892299 controls), of appendicular lean mass (ALM, 450243 participants), and of hand grip strength (exposure: 360000 participants; outcome: 334925 participants).


We identified a negative association of depression with lower ALM [odds ratio (OR): 0.932, 95% confidence interval (95%CI): 0.889-0.979, P = 0.005]. In the reverse MR analysis, we also observed an inverse association of hand grip strength with depression (OR: 0.200, 95%CI: 0.108-0.370, P < 0.001). Similar results were obtained in sensitivity analyses.


Depression was causally related to decreased muscle mass, and declined muscle strength might lead to a higher risk of depression.

Keywords: Appendicular lean mass, Depression, Hand grip strength, Mendelian randomization, Older adults, Sarcopenia

Core Tip: In this Mendelian randomization study, we established a bidirectional relationship between depression and reduced muscle mass, specifically lower appendicular lean mass and hand grip strength. Our findings highlight a potential bidirectional relationship between depression and sarcopenia with implications for both mental and physical health.