Electroconvulsive therapy exerts mainly acute molecular changes in serum of major depressive disorder patients.

Electroconvulsive therapy (ECT) is mainly used to treat medication resistant major depressive disorder (MDD) patients, with a remission rate of up to 90%. However, little is known about the serum molecular changes induced by this treatment. Understanding the mechanisms of action of ECT at the molecular level could lead to identification of response markers and potential new drug targets for more effective antidepressant treatments. We have carried out a pilot study which analysed serum samples of MDD patients who received a series of ECT treatments over 4 weeks. Patients received only ECT treatments over the first two weeks and a combination of ECT and antidepressant drugs (AD) over the subsequent two weeks. Blood serum analyses were carried out using a combination of multiplex Human MAP® immunoassay and liquid-chromatography mass spectrometry (LC-MS(E)) profiling. This showed that ECT had a predominant acute effect on the levels of serum proteins and small molecules, with changes at the beginning of ECT treatment and after administration of the ECT+AD combination treatment. This suggested a positive interaction between the two types of treatment. Changed molecules included BDNF, CD40L, IL-8, IL-13, EGF, IGF-1, pancreatic polypeptide, SCF, sortilin-1 and others which have already been implicated in MDD pathophysiology. We conclude that ECT appears to exert mainly acute effects on serum molecules.

Proteomic changes induced by anaesthesia and muscle relaxant treatment prior to electroconvulsive therapy.

PURPOSE: Electroconvulsive therapy (ECT) is a psychiatric treatment in which seizures are electrically induced in patients. Prior to treatment, patients are usually given short-acting anaesthetics and muscle relaxants to avoid harm, e.g. musculoskeletal injury, during the convulsions. However, most molecular studies investigating the mechanism of action of ECT have not explored the potential effects of the pre-treatment with anaesthetic and/ or muscle relaxant. EXPERIMENTAL DESIGN: We have carried out a targeted proteome analysis using multiplex immunoassay platform of serum samples before and 10 min after initiating the administration of the anaesthetic methohexital(®) and the muscle relaxant succinylcholine(®) to eight major depressive disorder patients undergoing ECT. RESULTS: Twenty-six out of 142 analysed molecules showed significant differences in abundance after the methohexital/succinylcholine treatment. Importantly, eight of these molecules (fatty acid-binding protein, insulin, interleukin (IL)1ß, IL-10, IL-4, prolactin, S100 calcium-binding protein B and tumor necrosis factor α) have been associated previously with effects of ECT. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicate that caution should be used when interpreting results in existing and future proteome-based biomarkers studies on the effects of ECT in neuropsychiatric disease or the use of anaesthetic/muscle relaxant in major surgical operations related to different therapeutic areas.