ECT and ACC GABA

Out on PubMed, from researchers in Norway and the USA, is this study:Anterior cingulate gamma-aminobutyric acid concentrations and electroconvulsive therapy.

Erchinger VJ, Miller J, Jones T, Kessler U, Bustillo J, Haavik J, Petrillo J, Ziomek G, Hammar Å, Oedegaard KJ, Calhoun VD, McClintock SM, Ersland L, Oltedal L, Abbott CC.Brain Behav. 2020 Sep 17:e01833. doi: 10.1002/brb3.1833. Online ahead of print.PMID: 32940003
The abstract is copied below:

Objective: The anticonvulsant hypothesis posits that ECT's mechanism of action is related to enhancement of endogenous anticonvulsant brain mechanisms. Results of prior studies investigating the role of the inhibitory neurotransmitter gamma-aminobutyric acid ("GABA+", GABA and coedited macromolecules) in the pathophysiology and treatment of depression remain inconclusive. The aim of our study was to investigate treatment-responsive changes of GABA+ in subjects with a depressive episode receiving electroconvulsive therapy (ECT).

Methods: In total, 41 depressed subjects (DEP) and 35 healthy controls (HC) were recruited at two independent sites in Norway and the USA. MEGA-PRESS was used for investigation of GABA+ in the anterior cingulate cortex. We assessed longitudinal and cross-sectional differences between DEP and HC, as well as the relationship between GABA+ change and change in depression severity and number of ECTs. We also assessed longitudinal differences in cognitive performance and GABA+ levels.

Results: Depressive episode did not show a difference in GABA+ relative to HC (t71 = -0.36, p = .72) or in longitudinal analysis (t36 = 0.97, p = .34). Remitters and nonremitters did not show longitudinal (t36 = 1.12, p = .27) or cross-sectional differences in GABA+. GABA+ levels were not related to changes in antidepressant response (t35 = 1.12, p = .27) or treatment number (t36 = 0.05, p = .96). An association between cognitive performance and GABA+ levels was found in DEP that completed cognitive effortful testing (t18 = 2.4, p = .03).

Conclusion: Our results failed to support GABA as a marker for depression and abnormal mood state and provide no support for the anticonvulsant hypothesis of ECT. ECT-induced change in GABA concentrations may be related to change in cognitive function.

Keywords: depression; electroconvulsive therapy; gamma-aminobutyric acid; magnetic resonance spectroscopy.

The pdf is here.

This collaborative study (2 sites: Haukeland University Hospital, Bergen, Norway and University of New Mexico Hospital, Albuquerque, New Mexico, USA) adds to the evidence base of brain GABA dynamics in depression and depression treatment. These are very technically complex studies to carry out, with multiple, hard-to-control variables possibly influencing the results. The sample size is modest by absolute standards, but quite large for this type of study. The mostly negative findings are disappointing, but not necessarily unexpected, given the intricacies of studying inhibitory neurotransmitter function throughout the brain (see authors' limitations section of the paper).

The one positive finding, that effortful cognitive performance declines with increasing GABA, is fascinating, and hopefully will be the subject of replication studies.

It remains clear that ECT has powerful anticonvulsant properties; the elucidation of the underlying mechanism(s) awaits further research.

The authors are to be complimented for their painstakingly careful and sophisticated investigation. Their data, both negative and positive, are important to have in the literature.

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