GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study

Neuropsychobiology. 2024;83(1):17-27. doi: 10.1159/000535512. Epub 2023 Dec 27.

Abstract

Introduction: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls.

Methods: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability.

Results: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT.

Conclusion: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Keywords: Intracortical facilitation; Long-interval intracortical inhibition; N-methyl-D-asparate; Paired pulse transcranial magnetic stimulation; Short-interval intracortical inhibition.

MeSH terms

  • Cortical Excitability*
  • Depressive Disorder, Major* / diagnostic imaging
  • Evoked Potentials, Motor
  • Humans
  • Neural Inhibition / physiology
  • Positron-Emission Tomography
  • Receptors, GABA-A
  • Transcranial Magnetic Stimulation
  • gamma-Aminobutyric Acid

Substances

  • Receptors, GABA-A
  • gamma-Aminobutyric Acid

Grants and funding

This research was supported by unrestricted grants from the Swedish Research Council (Grant No. 2016–02,362), the Swedish Society of Medicine, and Märta and Nicke Nasvell Foundation. R.B. was supported by a Gullstrand Research Fellow grant from Uppsala University Hospital. J.P. was supported by a postdoctoral grant from the Swedish Brain Foundation, and D.F. by the Swedish Brain Foundation (Grant No. PS2021-0026) and the Swedish Society for Medical Research (SSMF, Grant No. PD21-0136). The study was also supported by grants from Stiftelsen Professor Bror Gadelius Minnesfond (L.S., E.T.) and Fredrik och Ingrid Thurings Stiftelse (E.T.). Funding sources did not have any role in study design, analyses, interpretation of the data, writing of the report, or decision to submit the results.