Inflammation and Improvement of Depression Following Electroconvulsive Therapy in Treatment-Resistant Depression

Abstract

Objective Electroconvulsive therapy (ECT) is the most robust acute treatment for severe major depressive disorder, yet clinical response is variable. Inflammation is associated with depression, especially in women, and levels of C-reactive protein (CRP) and interleukin-6 (IL-6) predict response to antidepressant medications. This study evaluated whether markers of inflammation predicted response to electroconvulsive therapy (ECT) in patients with treatment resistant depression, and to what extent this association differed between men and women. Methods In patients (n=29) with a current major depressive episode diagnosed using DSM-IV-TR criteria, undergoing ECT at an academic referral center, levels of CRP, IL-6, IL-8, tumor necrosis factor (TNF)-α, and severity of depressive symptoms (Montgomery-Asberg Depression Rating Scale, MADRS) were prospectively evaluated before ECT treatment, after the second ECT session, and again at the completion of the index treatment series. Data were collected between 12/2011 and 12/2014. The primary outcome was end-of-treatment MADRS score. Results In multivariate analyses, higher levels of IL-6 at baseline, but not other inflammatory markers or clinical variables, were associated with lower end-of-treatment MADRS score (p=0.01). When stratified by sex, IL-6 remained a significant predictor of end-of-treatment MADRS for women (p=0.02) but not men (p=0.1), and CRP emerged as a significant predictor for women (p=0.04) but not men (p=0.66). CRP and IL-6 increased from baseline to the second ECT session (p’s<0.01) and returned to baseline levels at end of treatment; these changes did not relate to MADRS score over the course of ECT. Conclusions Levels of IL-6 prior to ECT treatment may be useful in identifying those depressed patients most likely to benefit from ECT treatment. In contrast, acute changes in IL-6 and CRP may reflect spikes in inflammatory response related to the initiation of seizure therapy, but not mood. Assessment of pre-treatment inflammatory biomarkers, especially in women, might be useful in guiding treatment decision-making in treatment resistant depression.

Role of Interleukin-6 in Depressive Disorder

“…However, the baseline IL-6 levels decreased among remitters after repeated ECT treatment. The findings are replicated by the following study and further demonstrated that IL-6 levels prior to ECT treatment may be a useful marker in identifying those MDD patients most likely to respond to ECT treatment [120].…”

Moderators for depressed mood and systemic and transcriptional inflammatory responses: a randomized controlled trial of endotoxin

“…Some depressed patients show elevated levels of systemic inflammatory markers [7], along with increased expression of inflammationrelated genes in monocytes or peripheral blood mononuclear cells [8,9]. Moreover, among the substantial minority (i.e., about 30%) of patients with elevated levels of inflammation [10], treatment response varies along with inflammation [10][11][12][13].…”

Effects of Electroconvulsive Therapy on Depression and Its Potential Mechanism

“…Lower promoter methylation rates of BDNF exon I were strictly associated with remission (Kleimann et al, 2015), and the CC genotype of BDNF polymorphism C270T contributed a useful response (Huuhka et al, 2007). In support of inflammation, higher levels of IL-6 at baseline anticipated profound depression relief, especially in females (Kruse et al, 2018), and the degree of change in serum matrix metalloproteinase-9 (MM-9) was associated with relapse following ECT (Shibasaki et al, 2018).…”

“…In short, in the elderly (Husain et al, 2004), psychotic symptom comorbidities (Husain et al, 2004), postpartum depression (Rundgren et al, 2018), shorter episode duration and more severe depressive symptoms (van Diermen et al, 2018), early depression alleviation (Birkenhager et al, 2019), lower NAA levels in the dACC at baseline (Njau et al, 2017), low genetic risk load (Foo et al, 2019), genetic or epigenetic modifications (Huuhka et al, 2007;Kleimann et al, 2015;Lin et al, 2015), and high baseline serum IL-6 levels (Kruse et al, 2018) and a serum MM-9 profile (Shibasaki et al, 2018) were more likely to benefit ECT recipients. Moreover, the subfield index of hippocampus and neural network plasticity (Abbott et al, 2014;Ota et al, 2015;van Waarde et al, 2015;Redlich et al, 2016;Cao et al, 2018;Nuninga et al, 2019) may provide precise evidence to predict the outcome.…”