Magnetic Resonance Spectroscopy in Depressed Subjects Treated With Electroconvulsive Therapy—A Systematic Review of Literature

Abstract

Electroconvulsive therapy (ECT) is considered to be the most effective acute treatment for otherwise treatment resistant major depressive episodes, and has been used for over 80 years. Still, the underlying mechanism of action is largely unknow. Several studies suggest that ECT affects the cerebral neurotransmitters, such as gamma-aminobutyric acid (GABA) and glutamate. Magnetic resonance spectroscopy (MRS) allows investigators to study neurotransmitters in vivo, and has been used to study neurochemical changes in the brain of patients treated with ECT. Several investigations have been performed on ECT-patients; however, no systematic review has yet summarized these findings. A systematic literature search based on the Prisma guidelines was performed. PubMed (Medline) was used in order to find investigations studying patients that had been treated with ECT and had undergone an MRS examination. A search in the databases Embase, PsycInfo, and Web of Science was also performed, leading to no additional records. A total of 30 records were identified and screened which resulted in 16 original investigations for review. The total number of patients that was included in these studies, ignoring potential overlap of samples in some investigations, was 325. The metabolites reported were N-acetyl aspartate, Choline, Myoinositol, Glutamate and Glutamine, GABA and Creatine. The strongest evidence for neurochemical change related to ECT, was found for N-acetyl aspartate (reduction), which is a marker of neuronal integrity. Increased choline and glutamate following treatment was also commonly reported.

Neural excitation/inhibition imbalance and the treatment of severe depression

“…Additionally, we provide strong evidence that ECT effectiveness did not depend on changes in regional self-inhibition. This is compatible with previous null findings in studies using frequentist statistics 41 . However, the classical statistics used in these studies were not able to provide conclusive evidence on the absence of an association between GABA concentrations and ECT effectiveness.…”

“…ECT did not seem to affect the strength of neural inhibition in our patients, when compared to changes in inhibition over time in healthy controls (although evidence was weak). Some magnetic resonance spectroscopy (MRS) studies showed increase of inhibitory GABA concentrations over the ECT-course, but adding healthy controls diminished these significant findings 41 . Additionally, we provide strong evidence that ECT effectiveness did not depend on changes in regional self-inhibition.…”

The Neurobiological Effects of Electroconvulsive Therapy Studied Through Magnetic Resonance: What Have We Learned, and Where Do We Go?

“…Although results are mixed (55,(93)(94)(95)(96)(97)(98)(99)(100)(101), and many studies do not report on all metabolites within the spectra, a reduction in N-acetylaspartate (NAA) was reported in six studies (55,95,(98)(99)(100)(101). The finding is difficult to reconcile with a theory that only comprises plasticity enhancing effects (102). A decrease in NAA is often paralleled by an increase in choline in clinical radiology, and increased choline has indeed been reported by some proton magnetic resonance spectroscopy investigations (93,94,101) after ECT.…”

Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases

“…Whilst exercise is unequivocally effective in reducing depression symptoms, other non-pharmacological glutaminergic-based treatments gaining evidence up to the systematic review level that may operate through this pathway are transcranial magnetic stimulation, electroconvulsive therapy, and deep brain stimulation [ 86 , 87 , 88 ].…”