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–MSE) 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.
Electroconvulsive therapy (ECT) is usually administered to patients with severe and medication-resistant major depression (refractory depression), mania, catatonia and acute schizophrenia (Mathew, 2005). In the short-term, ECT results in remission rates of 70–90% (Petrides et al., 2001 and Sackeim et al., 1993), which is higher than standard antidepressant treatments. Further advantages of ECT include faster improvement and better symptomatic remission. However, ECT has limitations including cognitive side effects and high relapse rates (Mathew, 2005), although some patients receive continuation of ECT for relapse prevention (Kellner et al., 2006). However, most patients treated with ECT receive antidepressant drug (AD) medication as maintenance therapy which reduces the relapse rate (reviewed in Bourgon and Kellner, 2000).
The primary therapeutic effect of ECT is a seizure induced by electrical stimulus. Little is known about the molecular mechanism of action or whether ECT and AD treatments have similar effects. Molecules in several brain areas are affected by ECT, including neurotransmitters, neuropeptides and neurotrophic factors (Wahlund and von Rosen, 2003). Consistent with effects on growth factors, pre-clinical studies have shown that electroconvulsive shock leads to increased hippocampal neurogenesis (Scott et al., 2000), angiogenesis (Newton et al., 2006) and glial proliferation in frontal cortex (Ongur et al., 2007). Also, ECT has been found to increase sympathetic vagal activity (Bar et al., 2010), marked by increased levels of pancreatic polypeptide (PPP). PPP levels have therefore been used as a biomarker for estimating the degree of ECT-stimulated vagal activity.
Here, we have carried out a pilot study to investigate the molecular changes in MDD patients after acute and chronic ECT, and by combined ECT and AD treatment. Sera were subjected to molecular profiling analyses using a combination of multiplex immunoassay and liquid-chromatography mass spectrometry (LC–MSE) approaches. This multiplex profiling approach was used to eliminate variability across individual measurements, thereby allowing reliable identification of molecules which are co-regulated within and across molecular pathways.
