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: major depressive disorder, modified electroconvulsive therapy, hypoxia-inducible factor, neuroinflammation, oxidative stress