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Glutamate Alterations Associated With Transcranial Magnetic Stimulation in Youth Depression: A Case Series

Yang, Xiao-Ru BSc*; Kirton, Adam MD†‡; Wilkes, Thomas Christopher MD*†; Pradhan, Sarah*; Liu, Irene MSc§; Jaworska, Natalia PhD*; Damji, Omar MSc†‡; Keess, Jamie BSc†‡; Langevin, Lisa Marie PhD*; Rajapakse, Thilinie MD†‡; Lebel, Robert Marc PhD; Sembo, Mariko BSc*; Fife, Marilyn RN*; MacMaster, Frank P. PhD*†

doi: 10.1097/YCT.0000000000000094
Original Studies

Objective: We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after 3 weeks of repetitive transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms.

Methods: We report 6 patients (4 females) 15 to 21 years of age with treatment-resistant MDD. Participants had a mean (SD) age of 18.7 (1.95) years and a mean (SD) IQ of 102.3 (3.39). Short echo proton magnetic resonance spectroscopy (1H-MRS) was used to quantify glutamate levels in the left DLPFC (4.5 cc) before and after rTMS treatment. Repetitive transcranial magnetic stimulation was localized to the left DLPFC and applied for 15 consecutive weekdays (120% resting motor threshold; 40 pulses over 4 seconds [10 Hz]; intertrain interval, 26 seconds; 75 trains; 3000 pulses). Treatment response was defined as a greater than 50% reduction in Hamilton Depression Rating Scale scores. Short echo proton magnetic resonance spectroscopy data were analyzed with LCModel to determine glutamate concentration.

Results: After rTMS, treatment responders (n = 4) showed an increase (relative to baseline) in left DLPFC glutamate levels (11%), which corresponded to an improvement in depressive symptom severity (68% Hamilton Depression Rating Scale score reduction). Treatment nonresponders (n = 2) had elevated baseline glutamate levels compared to responders in that same region, which decreased with rTMS (−10%). Procedures were generally well tolerated with no adverse events.

Conclusions: Repetitive transcranial magnetic stimulation is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement.

From the Departments of *Psychiatry, †Pediatrics, ‡Clinical Neuroscience, §Psychology, University of Calgary and ∥General Electric Applications and Workflow, GE Healthcare.

Received for publication October 3, 2013; accepted October 30, 2013.

Reprints: Frank MacMaster, PhD, Pediatric Mental Health, Departments of Psychiatry and Pediatrics, University of Calgary, Behavioral Research Unit, Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary AB T3B 6A8 (e-mail:

Dr. MacMaster received support for this research from the Children’s Hospital Aid Society and in part from the Cuthbertson and Fischer Chair in Paediatric Mental Health, the Alberta Children’s Hospital Foundation, Alberta Children’s Hospital Research Institute for Child and Maternal Health, the Mathison Centre for Mental Health Research and Education, the Hotchkiss Brain Institute, and the University of Calgary.

The authors declare no conflicts of interest.

© 2014 by Lippincott Williams & Wilkins