Yun YJ, Zhang Q, Zhao WX, Fan N, Wang ZR, An HM, Yang FD. Cognitive impairment and pain in depression: The mediating role of the kynurenine pathway. World J Psychiatry 2025; 15(11): 110690 [DOI: 10.5498/wjp.v15.i11.110690]
Corresponding Author of This Article
Fu-De Yang, MM, Professor, Beijing Huilongguan Hospital, Peking University, No. 7 Nandian Road, Changping District, Beijing 100096, China. yangfd2002@163.com
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Psychiatry
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Observational Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Nov 19, 2025 (publication date) through Nov 3, 2025
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World Journal of Psychiatry
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2220-3206
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Yun YJ, Zhang Q, Zhao WX, Fan N, Wang ZR, An HM, Yang FD. Cognitive impairment and pain in depression: The mediating role of the kynurenine pathway. World J Psychiatry 2025; 15(11): 110690 [DOI: 10.5498/wjp.v15.i11.110690]
World J Psychiatry. Nov 19, 2025; 15(11): 110690 Published online Nov 19, 2025. doi: 10.5498/wjp.v15.i11.110690
Cognitive impairment and pain in depression: The mediating role of the kynurenine pathway
Ya-Jun Yun, Qi Zhang, Wen-Xuan Zhao, Ning Fan, Zhi-Ren Wang, Hui-Mei An, Fu-De Yang
Ya-Jun Yun, Wen-Xuan Zhao, Ning Fan, Zhi-Ren Wang, Hui-Mei An, Fu-De Yang, Beijing Huilongguan Hospital, Peking University, Beijing 100096, China
Qi Zhang, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi 214151, Jiangsu Province, China
Co-corresponding authors: Hui-Mei An and Fu-De Yang.
Author contributions: Yun YJ designed the study and drafted manuscript; Zhang Q designed the study; Zhao WX and Fan N were responsible for investigation; Wang ZR was responsible for data curation and analysis; An HM and Yang FD were responsible for writing review and editing as the co-corresponding authors; all of the authors read and approved the final version of the manuscript to be published.
Supported by Grants from Beijing Municipal Science and Technology Commission, No. Z191100006619020; Beijing Municipal Administration of Hospitals Incubating Program, 2023, No. PX2023070; and Beijing Municipal Administration of Hospitals Incubating Program, 2024, No. PX2024072.
Institutional review board statement: This study was received ethical approval from the Institutional Review Board of Beijing Huilongguan Hospital (Beijing Huilongguan Ethics Committee, No. 2019-43).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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.
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/
Received: June 13, 2025 Revised: July 29, 2025 Accepted: September 4, 2025 Published online: November 19, 2025 Processing time: 144 Days and 4.3 Hours
Abstract
BACKGROUND
The tryptophan-kynurenine (TRP-KYN) pathway may be implicated in the pathophysiology of cognitive impairment and pain severity in major depressive disorder (MDD); however, few studies have explored the intricacies of their interaction.
AIM
To investigate the relationship between the TRP-KYN pathway and cognitive function in MDD patients with and without painful physical symptoms (PPS).
METHODS
Seventy patients with MDD were recruited, including 33 and 37 with and without PSS, respectively. The Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Short-form of McGill pain questionnaire (SFMPQ) were used to assess clinical symptoms. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB) score. TRP-KYN pathway metabolites’ serum levels were measured using high-performance liquid chromatography-tandem mass spectrometry.
RESULTS
The with PPS group exhibited significantly higher TRP-KYN ratios than did the without PPS group; in the former, the SFMPQ scores positively and negatively correlated with the TRP-KYN ratio and total MCCB score, respectively. Regression analysis indicated that body mass index and SFMPQ scores were significantly associated with the TRP-KYN ratio, predicting 30% of the variance.
CONCLUSION
The TRP-KYN ratio is a potential biomarker for identifying patients with depression accompanied by pain symptoms, and targeting it may represent a novel therapeutic strategy for managing pain in these individuals. Further elucidation of the biological mechanisms underlying cognitive impairment in MDD patients with PPS is warranted.
Core Tip: This study explores the relationship between the tryptophan-kynurenine (TRP-KYN) pathway and cognitive function in major depressive disorder (MDD) patients with and without painful physical symptoms. By analyzing serum metabolites and clinical assessments, we found that KYN level and TRP/KYN ratio were associated with pain severity but not with cognitive performance. These findings highlight the potential dissociation between pain-related and cognitive mechanisms in MDD and underscore the need for further studies on the biopsychosocial underpinnings of depression-related cognitive dysfunction.
