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. 2021 May 11:12:665402.
doi: 10.3389/fpsyt.2021.665402. eCollection 2021.

Intermittent Theta-Burst Stimulation Transcranial Magnetic Stimulation Increases GABA in the Medial Prefrontal Cortex: A Preliminary Sham-Controlled Magnetic Resonance Spectroscopy Study in Acute Bipolar Depression

Chad Diederichs  1 , Marilena M DeMayo  1   2   3   4   5   6 , Jaeden Cole  1   2   3 , Lakshmi N Yatham  7 , Ashley D Harris  2   4   5   6 , Alexander McGirr  1   2   3
Affiliations

Intermittent Theta-Burst Stimulation Transcranial Magnetic Stimulation Increases GABA in the Medial Prefrontal Cortex: A Preliminary Sham-Controlled Magnetic Resonance Spectroscopy Study in Acute Bipolar Depression

Chad Diederichs et al. Front Psychiatry. .

Abstract

Background: Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric acid (GABA) alterations in mood disorders, particularly in the medial prefrontal cortex (mPFC) where decreased concentrations have been associated with anhedonia. In major depressive disorder (MDD), prior work suggests that repetitive transcranial magnetic stimulation (rTMS) increases mPFC GABA concentrations proportional to antidepressant response. To our knowledge, this has not been examined in acute bipolar depression. Methods: As part of a multicentre 4-week randomized, double-blind, sham-controlled trial using intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex (DLPFC) in individuals with acute bipolar depression, we quantified mPFC GABA and Glx (glutamate+glutamine) concentrations using a 3T MRS scan at baseline and after the intervention. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale-17 (HRDS-17), and anhedonia was measured using the Snaith-Hamilton Pleasure Scale (SHAPS). Results: The trial was terminated for futility and magnetic resonance spectroscopy data was acquired for 18 participants. At baseline, there were no associations between GABA or Glx concentrations and anhedonia, however GABA was negative correlated with depressive symptom severity on the HRDS-17. Compared to the sham-iTBS group, participants receiving active-iTBS had a significant increase in mPFC GABA concentrations. This was unrelated to antidepressant outcomes or improvements in anhedonia. Conclusion: Our data suggests that iTBS targeting the DLPFC is associated with physiological changes in the mPFC. In acute bipolar depression, our preliminary data suggests that mPFC GABA is dissociated from antidepressant iTBS treatment outcomes and anhedonia.

Keywords: bipolar depression; bipolar disorder; gamma-aminobutyric acid; intermittent theta burst stimulation; magnetic resonance spectroscopy; repetitive transcranial magnetic stimulation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Representative T1 weighted image with mPFC voxel placement and GABA-edited MEGAPRESS.
Figure 2
Figure 2
CONSORT flow diagram.
Figure 3
Figure 3
(A) Baseline mPFC GABA concentrations were negative associated with HRDS-17 scores. (B) Active-iTBS, but not sham-iTBS, was associated with an increase in mPFC GABA concentrations after 4 weeks of treatment. *time interaction p < 0.05.
See this image and copyright information in PMC

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