Observational Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Mar 19, 2025; 15(3): 102567
Published online Mar 19, 2025. doi: 10.5498/wjp.v15.i3.102567
Serum homocysteine showed potential association with cognition and abnormal gut microbiome in major depressive disorder
Chen-Chen Xu, Wen-Xuan Zhao, Yu Sheng, Ya-Jun Yun, Ting Ma, Ning Fan, Jia-Qi Song, Jun Wang, Qi Zhang
Chen-Chen Xu, Jun Wang, Qi Zhang, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
Wen-Xuan Zhao, Ya-Jun Yun, Ting Ma, Ning Fan, Jia-Qi Song, Department of Psychiatry, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
Yu Sheng, Department of Psychiatry, Chinese People’s Liberation Army Unit 94710, Wuxi 214141, Jiangsu Province, China
Jun Wang, Qi Zhang, Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi 214151, Jiangsu Province, China
Co-first authors: Chen-Chen Xu and Wen-Xuan Zhao.
Co-corresponding authors: Jun Wang and Qi Zhang.
Author contributions: Zhao WX, Yun YJ, Ma T, Zhang Q, Fan N, and Sheng Y collected and interpreted patient data; Sheng Y analyzed the data; Xu CC and Zhang Q were significant contributors to the writing of the manuscript; Zhang Q and Wang J organized and supported this study; Xu CC, Zhao WX, Sheng Y, Yun YJ, Ma T, Fan N, Song JQ, Wang J and Zhang Q have read and approved the final version of the manuscript.
Supported by the Wuxi Municipal Health Commission Youth Fund Project, No. Q202268; Wuxi Scientific and technological breakthrough of “Light of the Taihu Lake” (Basic Research), No. K20221039; Jiangsu Shuangchuang Doctoral Program, No. JSSCBS20221991; Beijing Municipal Administration of Hospital Incubating Program, No. PX2023070 and No. PX2024072; Capital’s Funds for Health Improvement and Research, No. SF2024-4-2134; Beijing Hospitals Authority Youth Program, No. QML20232003; and the Top Talent Support Program for young and middle-aged people of Wuxi Health Committee, No. HB2023089.
Institutional review board statement: This study was approved by the Ethics Committee of the Beijing Huilongguan Hospital Symbiotics (No. 2019-43).
Informed consent statement: All participants provided informed consent before participating in the study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The data used in this study can be obtained from the corresponding author upon request.
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: Qi Zhang, PhD, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, No. 156 Qianrong Road, Binhu District, Wuxi 214151, Jiangsu Province, China. 1811110636@bjmu.edu.cn
Received: October 23, 2024
Revised: December 18, 2024
Accepted: January 6, 2025
Published online: March 19, 2025
Processing time: 127 Days and 1 Hours
Abstract
BACKGROUND

Cognitive impairment is one of the common clinical manifestations of depression, causing negative distress to patients. Elevated homocysteine (Hcy) concentrations and gut microbiome dysfunction may be observed in patients with depression.

AIM

To investigate the relationship between Hcy, microbiome, and cognition in depressive patients.

METHODS

We recruited 67 patients with major depressive disorder (MDD) (MDD group) and 94 healthy controls (HCs) individuals (HCs group). Serum Hcy levels were determined using the enzyme circulation method. 16s rRNA sequencing was used to classify and identify the fecal bacteria. 17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora, Hcy, and depressive cognitive function.

RESULTS

Elevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients with MDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, working memory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed a negative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was also significantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).

CONCLUSION

Our results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may be related to the physiological and pathological mechanisms underlying cognitive deficits in depression.

Keywords: Homocysteine; Microbiome; Intestinal flora; Gut microbiota; Gut–brain axis; Major depressive disorder; Cognitive function; Cognitive impairment

Core Tip: Cognitive impairment is common in patients with depression, who often exhibit elevated levels of homocysteine (Hcy) and abnormalities in gut microbiome. However, to date, no research has systematically investigated the relationship between Hcy, the microbiome, and cognition in depressive patients. Our study integrates results from functional predictive analysis, microbiome data, and clinical scale assessments, revealing a close association between Hcy levels, cognitive function, and gut microbiome, in major depressive disorder. These findings may contribute to elucidating the physiological and pathological mechanisms underlying cognitive deficits in depression, further supporting the brain-gut axis theory, and providing evidence for gut- microbiome-based therapeutic strategies.