title: Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy.
abstract: GABAergic and glutamatergic neurotransmitter systems are central to the pathophysiology of depression and are potential targets of repetitive transcranial magnetic stimulation (rTMS). We assessed the effect of 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) of patients with major depressive disorder on the levels of medial prefrontal cortex (MPFC) γ-aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) as assessed in vivo with proton magnetic resonance spectroscopy ((1)H MRS).
  
  
  
  Currently depressed individuals between the ages of 23 and 68 years participated in a 5-week naturalistic, open-label treatment study of rTMS, with (1)H MRS measurements of MPFC GABA and Glx levels at baseline and following 5 weeks of the rTMS intervention. We applied rTMS pulses over the left DLPFC at 10 Hz and 80%-120% of motor threshold for 25 daily sessions, with each session consisting of 3000 pulses. We assessed therapeutic response using the 24-item Hamilton Rating Scale for Depression (HAMD24). The GABA and Glx levels are expressed as ratios of peak areas relative to the area of the synchronously acquired and similarly fitted unsuppressed voxel water signal (W).
  
  
  
  Twenty-three currently depressed individuals (7 men) participated in the study. GABA/W in the MPFC increased 13.8% (p = 0.013) in all depressed individuals. There were no significant effects of rTMS on Glx/W. GABA/W and Glx/W were highly correlated in severely depressed patients at baseline but not after TMS.
  
  
  
  The primary study limitations are the open-label design and the inclusion of participants currently taking stable regimens of antidepressant medications.
  
  
  
  These results implicate GABAergic and glutamatergic systems in the mechanism of action of rTMS for major depression, warranting further investigation in larger samples.
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Dubin
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Xiangling
authors.initials: X
authors.lastname: Mao
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Samprit
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Kyle A B
authors.initials: KA
authors.lastname: Lapidus
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Guoxin
authors.initials: G
authors.lastname: Kang
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Conor
authors.initials: C
authors.lastname: Liston
authors.affiliation: From the Department of Psychiatry, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA (Dubin, Liston); the Department of Radiology, Weill Cornell Medical College, New York, USA (Mao, Kang, Shungu); the Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, USA (Banerjee); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA (Lapidus); and the Johns Hopkins University, Baltimore, USA (Goodman).
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
mesh_terms: D000328:Adult; D000368:Aged; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid