Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy

Abstract

Background Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. Methods 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48 hours after ECT series completion. Results At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-β than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-β levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-β changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT. Limitations As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. Conclusions Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-β, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotropin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation.

Low tumor necrosis factor‐α levels predict symptom reduction during electroconvulsive therapy in major depressive disorder

“…No similar correlations were found during subsequent sessions. No findings suggesting associations between a low TNFα level and symptom reduction during ECT have been reported in previous studies (First et al., 1996; Fluitman et al., 2011; Hestad et al., 2003; Rotter et al., 2013; Rush et al., 2016; Zincir et al., 2016). If replicated in the future studies, this finding supports the role of TNFα in the pathogenesis of MDD and in the mechanism of action of ECT; it may also guide the selection of treatment modalities for patients with severe MDD.…”

“…The effect of ECT on the TNFα level appears to be transitory because the TNFα level returned to the basic level before next ECT session. This finding differs from some previous reports in which the TNFα level either increased, did not change, or decreased by ECT (First et al., 1996; Fluitman et al., 2011; Hestad et al., 2003; Rotter et al., 2013; Rush et al., 2016; Zincir et al., 2016). The design of the study by Hestad et al.…”

“…They reported a decrease in the baseline TNFα level during the ECT series and 24 hr and 1 week after the last ECT session (Fluitman et al., 2011). Additionally, a decrease in the TNFα level was observed in a study in which measurements were taken 1 day before the ECT series, at the time of the clinical response to ECT, and 1 day after the series (Rush et al., 2016). In contrast, Fluitman et al.…”

“…Some studies have addressed the association between TNFα and ECT (First, Spitzer, Gibbon, & Williams, 1996; Fluitman et al., 2011; Hestad et al., 2003; Rotter et al., 2013; Rush et al., 2016; Zincir, Ozturk, Bilgen, Izci, & Yukselir, 2016). In 2003, Hestad et al.…”

“…Other studies have found no change in the TNFα level during or after the ECT series (First et al., 1996; Hestad et al., 2003; Zincir et al., 2016). A recent study revealed a decrease in the TNFα level during and after an ECT series, although the baseline TNFα level before ECT was lower in patients than in controls (Rush et al., 2016). …”