The Association Between Hypoxia Improvement and Electroconvulsive Therapy for Major Depressive Disorder

Zhida Bian; Hui Li; Yanlong Liu; Yanjun Cao; Yanxia Kang; Yongjun Yu; Feng Zhang; Cunbao Li; Yimin Kang; Fan Wang

doi:10.2147/NDT.S318919

The Association Between Hypoxia Improvement and Electroconvulsive Therapy for Major Depressive Disorder

Neuropsychiatr Dis Treat. 2021 Sep 22:17:2987-2994. doi: 10.2147/NDT.S318919. eCollection 2021.

Authors

Zhida Bian^#^{1

2}, Hui Li^#^{3

4}, Yanlong Liu^#⁵, Yanjun Cao², Yanxia Kang², Yongjun Yu², Feng Zhang^{1

2}, Cunbao Li¹, Yimin Kang¹, Fan Wang^{2

4}

Affiliations

¹ Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, 010110, People's Republic of China.
² Beijing Hui-Long-Guan Hospital, Peking University, Beijing, 100096, People's Republic of China.
³ Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, People's Republic of China.
⁴ Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital, Urumqi, 830063, People's Republic of China.
⁵ School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People's Republic of China.

^# Contributed equally.

Abstract

Background: The occurrence of depression was related with a state of mild hypoxia for a long time. Hypoxia-inducible factor-2α (HIF-2α) modulates the process from acute to chronic hypoxia, consequently regulating changes in inducible nitric oxide synthase (iNOS). Increasing levels of iNOS combined with major depressive disorder (MDD) have been associated with the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which increase the severity of depression.

Objective: The aim was to investigate whether depressive symptoms might be improved by regulating HIF-2α levels to decrease the degree of oxidative stress and inflammation using electroconvulsive therapy (ECT).

Methods: In this observational study, 49 MDD patients were divided into the ECT group (n=32) and control group (n=17). The Hamilton Depression Rating Scale (HAMD) was used to evaluate depressive symptoms of patients at enrollment and after 2 weeks of treatment. The levels of HIF-2α, NOS, IL-6, and TNF-α in plasma were analyzed accordingly.

Results: The total score in each dimension of HAMD decreased more efficiently in the ECT group than in the control group (p < 0.05). The plasma levels of IL-6 in the ECT group were notably decreased after the 2-week treatment (t = 3.596, p = 0.001). The decreased trend to statistical significance of HIF-2α was observed after treatment in the ECT group (p = 0.091).

Conclusion: The present study demonstrated that the therapeutic effects of long-term ECT therapy for MDD may further benefit from and contribute to the improvement of MDD-associated chronic hypoxia.

Keywords: hypoxia-inducible factor; major depressive disorder; modified electroconvulsive therapy; neuroinflammation; oxidative stress.

Grants and funding

This work was supported by the following grants: The Technology Support Project of Xinjiang (2017E0267), Natural Science Foundation of Xinjiang Uyghur Autonomous Region (2018D01C228 and 2018D01C239), Tianshan Youth Project–Outstanding Youth Science and Technology Talents of Xinjiang (2017Q007), Natural Science Foundation of China (81560229 and 81760252), Beijing Natural Science Foundation (7152074), The 10th Inner Mongolia Autonomous Region ‘Prairie excellence’ Project, and the Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.