Jennifer G. Levitt1, Guldamla Kalender1, Joseph O’Neill1, Joel P. Diaz1, Ian A. Cook1, Nathaniel Ginder1, David Krantz1, Michael J. Minzenberg1, Nikita Vince-Cruz1, Lydia D. Nguyen1, Jeffry R. Alger1, Andrew F. Leuchter1. 1. From the Neuromodulation Division, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles (Levitt, Diaz, Cook, Ginder, Krantz, Minzenberg, Vince-Cruz, Nguyen, Leuchter); the Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles (Levitt, Kalender, O’Neill, Cook, Krantz, Minzenberg, Leuchter); the Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles (Kalender); the Division of Child and Adolescent Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles (Levitt, O’Neill); the Department of Bioengineering, Henry Samueli School of Engineering at Applied Science at UCLA, Los Angeles (Cook); the Department of Neurology, UCLA David Geffen School of Medicine at UCLA, Los Angeles (Alger); the Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas (Alger); and the NeuroSpectroScopics, LCC, Sherman Oaks, California (Alger).
Abstract
Background: The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPFC). Methods: In 26 adults with TRD, we used Mescher–Garwood point-resolved spectroscopy (MEGA-PRESS) spectral-editing MRS to measure GABA in the left DLPFC before and after standard clinical treatment with rTMS. All participants but 1 were medicated, including 12 patients on GABA agonist agents. Results: Mean GABA in the DLPFC increased 10.0% (p = 0.017) post-rTMS in the overall sample. As well, GABA increased significantly in rTMS responders (n = 12; 23.6%, p = 0.015) but not in nonresponders (n = 14; 4.1%, p = not significant). Changes in GABA were not significantly affected by GABAergic agonists, but clinical response was less frequent (p = 0.005) and weaker (p = 0.035) in the 12 participants who were receiving GABA agonists concomitant with rTMS treatment. Limitations: This study had an open-label design in a population receiving naturalistic treatment. Conclusion: Treatment using rTMS was associated with increases in GABA levels at the stimulation site in the left DLPFC, and the degree of GABA change was related to clinical improvement. Participants receiving concomitant treatment with a GABA agonist were less likely to respond to rTMS. These findings were consistent with earlier studies showing the effects of rTMS on GABA levels and support a GABAergic model of depression.
Background: The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPFC). Methods: In 26 adults with TRD, we used Mescher–Garwood point-resolved spectroscopy (MEGA-PRESS) spectral-editing MRS to measure GABA in the left DLPFC before and after standard clinical treatment with rTMS. All participants but 1 were medicated, including 12 patients on GABA agonist agents. Results: Mean GABA in the DLPFC increased 10.0% (p = 0.017) post-rTMS in the overall sample. As well, GABA increased significantly in rTMS responders (n = 12; 23.6%, p = 0.015) but not in nonresponders (n = 14; 4.1%, p = not significant). Changes in GABA were not significantly affected by GABAergic agonists, but clinical response was less frequent (p = 0.005) and weaker (p = 0.035) in the 12 participants who were receiving GABA agonists concomitant with rTMS treatment. Limitations: This study had an open-label design in a population receiving naturalistic treatment. Conclusion: Treatment using rTMS was associated with increases in GABA levels at the stimulation site in the left DLPFC, and the degree of GABA change was related to clinical improvement. Participants receiving concomitant treatment with a GABA agonist were less likely to respond to rTMS. These findings were consistent with earlier studies showing the effects of rTMS on GABA levels and support a GABAergic model of depression.
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