Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response

Abstract

Objective: Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients.

Methods: A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted.

Results: SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05).

Conclusions: Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.

Keywords: oxidative stress parameters; electroconvulsive therapy; treatment-resistant bipolar disorder.

Figure 1.

Oxidative stress parameters in patients and healthy controls at baseline. ANCOVA was applied to compare oxidative stress parameters (SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; CAT, catalase; MDA, malondialdehyde) between patients and controls adjusting for age. There were significant differences in the levels of SOD, GSH-Px, and MDA between patients and controls (all P = .001), whereas CAT levels were not significantly different (P > .05). trBD, treatment-resistant bipolar disorder.

Figure 2.

Oxidative stress parameters among treatment-resistant manic bipolar disorder (BD) patients, treatment-resistant depressive BD patients, and healthy controls at baseline. ANCOVA was applied to compare oxidative stress parameters (SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; CAT, catalase; MDA, malondialdehyde) among the 3 groups. Bonferroni corrections were applied to adjust for multiple testing. trBD-D, treatment-resistant bipolar disorder depression; trBD-M, treatment-resistant bipolar disorder mania.

Figure 3.

The association between catalase (CAT) levels and illness severity in patients with treatment-resistant bipolar disorder (tr-BD) depression at baseline. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale (HAMD-17) scores in patients with trBD depression (adjusted r = 0.83, P = .005).

Figure 4.

The effect of 6-week electroconvulsive therapy (ECT) treatment on oxidative stress parameters. Catalase (CAT) and malondialdehyde (MDA) levels decreased in responders after 6 weeks of ECT (P = .02 and P = .001, respectively), but the CAT levels did not change after Bonferroni correction for multiple tests. Red line represents the mean level of each parameter. Responders, patients who responded to ECT; nonresponders, patients who failed to respond to ECT.