PT - JOURNAL ARTICLE AU - Jennifer G. Levitt AU - Guldamla Kalender AU - Joseph O’Neill AU - Joel P. Diaz AU - Ian A. Cook AU - Nathaniel Ginder AU - David Krantz AU - Michael J. Minzenberg AU - Nikita Vince-Cruz AU - Lydia D. Nguyen AU - Jeffry R. Alger AU - Andrew F. Leuchter TI - Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy AID - 10.1503/jpn.180230 DP - 2019 Nov 01 TA - Journal of Psychiatry and Neuroscience PG - 386--394 VI - 44 IP - 6 4099 - http://jpn.ca/content/44/6/386.short 4100 - http://jpn.ca/content/44/6/386.full SO - J Psychiatry Neurosci2019 Nov 01; 44 AB - 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.