ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
Cognitive Impairment in Comorbid MDD and OSA: The Dual Effects of Intermittent Hypoxia and Sleep Fragmentation
Provisionally accepted
Jiajia Zhang1,2,3
Shuangshuang Ma4Tianqin Xie1,2,3Mingming Zheng1,2,3Shuai Ding1,2,3Jiakuai Yu1,2,3Peng Zhu5
Daomin Zhu1,2,3*- 1Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Hefei, China
- 2合肥市第四人民医院, 合肥市, China
- 3Anhui Mental Health Center, Hefei, China
- 4School of Nursing, Anhui Medical University, Hefei, China
- 5Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, China
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Objectives:Major depressive disorder (MDD) and obstructive sleep apnea (OSA) exhibit an elevated comorbidity rate. It is posited that in MDD, comorbid OSA exacerbates cognitive impairment through mechanisms including intermittent hypoxia and sleep continuity disruption (sleep architecture disruption and sleep fragmentation). Methods:This cross-sectional study eventually recruited 245 patients aged 18 to 60 years. The cohort included patients with MDD (n=136), MDD with mild OSA (MDD-MO, n=75), and MDD with moderate-to-severe OSA (MDD-SO, n=34). Clinical symptoms, nocturnal sleep, and cognitive function were assessed using clinical psychological scales, polysomnography (PSG), and the event-related potential P300, respectively. We evaluated the intergroup differences in P300 components and their correlation with sleep parameters. Results:Compared to the other two groups, the MDD-SO group exhibited significant increases in the Oxygen Desaturation Index (ODI), the proportion of N1 sleep and Microarousal Index (p < 0.05). The MDD-SO group showed a marked reduction in N3 and REM sleep compared to both the MDD-MO and MDD groups (P < 0.05 for both). Additionally, P300 latency was significantly prolonged in the MDD-MO and MDD-SO groups relative to the MDD group (P < 0.001). Multiple linear regression identified AHI and ODI as a significant positive predictor of P2, N2, P3a and P3b latency, and Microarousal Index as a significant positive predictor of N1, P2, P3a, and P3b latency in MDD patients with OSA (all p < 0.05). Conclusion:The observed associations between prolonged P300 latency and elevated ODI/Microarousal Index raises the possibility that intermittent hypoxia and sleep fragmentation are underlying contributing factors. These two nocturnal disturbances may interact to worsen cognitive dysfunction in patients with MDD-OSA comorbidity.
Keywords: intermittent hypoxia, Major depressive disorder (MDD), Obstructive sleep apnea (OSA), P300, Sleep continuity disruption
Received: 17 Aug 2025; Accepted: 02 Jan 2026.
Copyright: © 2026 Zhang, Ma, Xie, Zheng, Ding, Yu, Zhu and Zhu. 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: Daomin Zhu
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