title: Glutamate alterations associated with transcranial magnetic stimulation in youth depression: a case series.
abstract: 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.
authors.affiliation: From the Departments of *Psychiatry, †Pediatrics, ‡Clinical Neuroscience, §Psychology, University of Calgary and ∥General Electric Applications and Workflow, GE Healthcare.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Yang
authors.forename: Adam
authors.initials: A
authors.lastname: Kirton
authors.forename: Thomas Christopher
authors.initials: TC
authors.lastname: Wilkes
authors.forename: Sarah
authors.initials: S
authors.lastname: Pradhan
authors.forename: Irene
authors.initials: I
authors.lastname: Liu
authors.forename: Natalia
authors.initials: N
authors.lastname: Jaworska
authors.forename: Omar
authors.initials: O
authors.lastname: Damji
authors.forename: Jamie
authors.initials: J
authors.lastname: Keess
authors.forename: Lisa Marie
authors.initials: LM
authors.lastname: Langevin
authors.forename: Thilinie
authors.initials: T
authors.lastname: Rajapakse
authors.forename: Robert Marc
authors.initials: RM
authors.lastname: Lebel
authors.forename: Mariko
authors.initials: M
authors.lastname: Sembo
authors.forename: Marilyn
authors.initials: M
authors.lastname: Fife
authors.forename: Frank P
authors.initials: FP
authors.lastname: MacMaster
mesh_terms: D000293:Adolescent; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
chemical_list: D018698:Glutamic Acid