Anterior cingulate gamma-aminobutyric acid concentrations and electroconvulsive therapy

Brain Behav. 2020 Nov;10(11):e01833. doi: 10.1002/brb3.1833. Epub 2020 Sep 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Sectional Studies
  • Electroconvulsive Therapy*
  • Gyrus Cinguli*
  • Humans
  • Norway
  • gamma-Aminobutyric Acid


  • gamma-Aminobutyric Acid