ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1546733
This article is part of the Research TopicBrain-body Interactions Underlying Comorbid Depression and Other Mood DisordersView all 9 articles
Exploring the Relationship and Shared Mechanisms of Major Depressive Disorder and Diabetic Kidney Disease: A Comprehensive Clinical and Genetic Analysis
Provisionally accepted
Huan-Xi Liu1,2Ting-Ting Wang2You-Di Cheng2Chun-Hui Qu2
Shunkang Feng2Xiang-Wen Wang2
Xiaohui Wu3
Wenxi Sun4*
Ping Sun2*- 1Qingdao University, Qingdao, Shandong Province, China
- 2Qingdao Mental Health Center, Qingdao, China
- 3Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
- 4Suzhou Guangji Hospital, Suzhou, Jiangsu Province, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Major depressive disorder (MDD) is a common comorbidity in diabetes mellitus (DM), and diabetic kidney disease (DKD) is a severe complication of DM. This study explored the clinical and genetic associations between MDD and DKD, aiming to identify shared biomarkers, pathways, and immune features. Using data from the National Health and Nutrition Examination Survey (NHANES, 2005(NHANES, -2018)), we found a significant association between MDD and DKD (OR = 1.45, 95% CI: 1.28-1.64). Linkage Disequilibrium Score Regression (LDSC) showed a significant genetic correlation (r = 0.2153, P = 0.008), but Mendelian randomization (MR) analysis did not reveal a causal relationship. Gene expression analysis identified 83 crosstalk genes, primarily involved in inflammation and immune regulation. Protein-protein interaction (PPI) analysis identified eight hub genes, with CD163 and KLRB1 being the most promising as shared diagnostic biomarkers, confirmed by least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic (ROC) curves. Immune infiltration analysis highlighted immune cells associated with both diseases. Connectivity map (cMAP) analysis and molecular docking suggested rucaparib and levocetirizine as potential therapeutic agents. Our findings support a genetic and immunological link between MDD and DKD, with CD163 and KLRB1 as potential biomarkers and therapeutic targets.
Keywords: Major Depressive Disorder, Diabetic kidney disease, NHANES, genetic correlation, Transcriptomic Analysis
Received: 17 Dec 2024; Accepted: 15 Sep 2025.
Copyright: © 2025 Liu, Wang, Cheng, Qu, Feng, Wang, Wu, Sun and Sun. 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:
Wenxi Sun, wenxi_sun@126.com
Ping Sun, qdsunping99@sina.com
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.