ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Behavioral and Psychiatric Genetics
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1659330
Integrative Clinical and Molecular Insights into the Comorbidity Between Depression and Sleep Apnea Syndrome
Provisionally accepted
- 1Shanghai Jing'an District Shibei Hospital, Shanghai, China
- 2Shanghai Gonghui Hospital, Shanghai, China
- 3Australian Chinese Preventive Medicine Association, Croydon, Australia
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
Objective: To identify and characterize overlapping genes and pathways linking Depression and Sleep Apnea Syndrome (SAS).Methods: A three-level analysis was conducted. Clinically, depression severity in 29 SAS patients was assessed using the Zung Self-Rating Depression Scale. Molecularly, an AIdriven literature mining approach was applied to extract gene-disease associations from PubMed and bioinformatics databases (19,924 genes), with prioritization using the Adjusted Binomial Method and validation via differential expression analysis.Functionally, shared genes were explored through protein-protein interaction (PPI) networks, enrichment analysis, and directional pathway modeling.Results: Clinically, 62.07% of SAS patients exhibited depressive symptoms, with mild to moderate severity based on the Zung Self-Rating Depression Scale. Molecularly, 872 genes were found to be shared between 4,544 Depression-related and 1,197 SAS-related genes (OR = 11; p = 4.95 × 10⁻³¹⁹). Further prioritization identified 24 overlapping genes with strong enrichment (OR = 10.9; p = 3.32 × 10⁻¹⁶), supported by validation in multiple gene expression datasets. These genes formed a densely connected protein-protein interaction network (238 edges; density = 0.43; clustering coefficient = 0.87), with core hubs including CASP3, TP53, SOD2, HMOX1, and MIR146A. Enrichment analysis highlighted involvement in oxidative stress, ferroptosis, and inflammatory pathways. Directional pathway modeling indicated that SAS may influence Depression via 18 genes and vice versa via 5 genes, with MIF and SOD2 acting as shared regulators.This study reveals significant clinical and molecular links between Depression and SAS, identifying shared biological pathways and candidate targets for integrated therapeutic strategies.
Keywords: Depression, Sleep apnea syndrome, adjusted binomial method, pathways, Genetic connection
Received: 17 Jul 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Chen, Zhuang, Ji, Sun, Zhu, Wang and Wang. 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:
Bo Wang, Australian Chinese Preventive Medicine Association, Croydon, Australia
Jin Wang, Shanghai Jing'an District Shibei Hospital, Shanghai, 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.