Improvement of psychomotor retardation after electroconvulsive therapy is related to decreased IL-6 levels.

BACKGROUND: Prior studies suggest that IL-6 may be involved in the pathophysiology of psychomotor symptoms in depression. Electroconvulsive therapy (ECT), as yet the most effective biological treatment of severe depression, is known to improve psychomotor functioning, while recent studies have shown a decrease in the elevated IL-6 levels of depressed patients following ECT. OBJECTIVES: This study investigates whether the improvement in psychomotor functions in patients with depression after ECT is related to changes in IL-6 levels. METHODS: Peripheral IL-6 was quantified and the severity of psychomotor agitation and retardation determined using the CORE assessment of psychomotor symptoms in 62 patients with a (unipolar or bipolar) depressive episode within one week before and within one week after their course of ECT. RESULTS: IL-6 levels had decreased significantly following ECT and both psychomotor retardation and agitation had improved. The decrease in IL-6 levels was related to the improvement of psychomotor retardation, with post-hoc analysis revealing that higher baseline IL-6 levels positively correlated with higher psychomotor retardation scores. CONCLUSION: With this study, we provide the first evidence that the improvement of psychomotor retardation after ECT for depression is related to the immunomodulatory properties of the treatment, most specifically the decrease in IL-6 levels.

Inflammation, Hippocampal Volume, and Therapeutic Outcome following Electroconvulsive Therapy in Depressive Patients: A Pilot Study.

INTRODUCTION: Electroconvulsive therapy (ECT) influences the concentration of peripheral inflammatory markers, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In which way this immune effect contributes to the impact of ECT on the central nervous system in depression remains unknown. OBJECTIVE: The aim of this study was to examine whether the hippocampal volumetric increase in depressed patients treated with ECT is related to changes in peripheral IL-6 and TNF-α levels. METHODS: IL-6 and TNF-α plasma levels were measured in 62 patients 1 week before and after an acute course of ECT. Hippocampal volumes were analyzed in a magnetic resonance imaging (MRI) subsample of 13 patients at the same time points. RESULTS: A significant decrease in IL-6 levels was observed in the total sample and a significant increase in hippocampal volume in the MRI subsample. The reduction of peripheral IL-6 correlated with an increase in total hippocampal volume. A more limited decrease of TNF-α correlated with a more limited increase of both the total and left hippocampus volumes. CONCLUSION: This pilot study is the first to highlight the link between peripheral immune changes and hippocampal volume increase following ECT. Further research is required to conclude whether ECT indeed exerts its central effect on the brain via changes of peripheral inflammatory markers.

A mood state-specific interaction between kynurenine metabolism and inflammation is present in bipolar disorder.

OBJECTIVES: Cytokines are thought to contribute to the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) and studied their relation to kynurenine metabolites and mood. METHODS: Patients with BD suffering from an acute mood episode were assigned to the depressive (n = 35) or (hypo)manic (n = 32) subgroup. Plasma levels of inflammatory markers [cytokines, C-reactive protein] and kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KYNA)] were measured on 6 time points during 8 months follow-up. Biological marker levels in patients were compared to controls (n = 35) and correlated to scores on mood scales. Spearman correlations and linear mixed models were used for statistical analysis. RESULTS: Twenty patients of the manic subgroup, 29 of the depressive subgroup, and 30 controls completed the study. The manic subgroup had a rapid remission of mood symptoms, but in the depressive subgroup subsyndromal symptoms persisted. No differences in inflammation were found between groups. A strong correlation between tumor necrosis factor-α and KYN, KYN/TRP, 3-HK and QA (ρ > 0.60) was specific for the manic group, but only at baseline (during mania). The depressive subgroup had a lower neuroprotective ratio (KYNA/3-HK, P = .0004) and a strong association between interferon-y and kynurenine pathway activation (P < .0001). KYNA was low in both patient groups versus controls throughout the whole follow-up (P = .0008). CONCLUSIONS: Mania and chronic depressive symptoms in BD are accompanied by a strong interaction between inflammation and a potentially neurotoxic kynurenine metabolism.