PMID- 26900793 OWN - NLM STAT- MEDLINE DCOM- 20180104 LR - 20220410 IS - 1488-2434 (Electronic) IS - 1180-4882 (Print) IS - 1180-4882 (Linking) VI - 41 IP - 3 DP - 2016 Apr TI - Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy. PG - E37-45 AB - BACKGROUND: 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) gamma-aminobutyric acid (GABA) and the combined resonance of glutamate and glutamine (Glx) as assessed in vivo with proton magnetic resonance spectroscopy ((1)H MRS). METHODS: 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). RESULTS: 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. LIMITATIONS: The primary study limitations are the open-label design and the inclusion of participants currently taking stable regimens of antidepressant medications. CONCLUSION: These results implicate GABAergic and glutamatergic systems in the mechanism of action of rTMS for major depression, warranting further investigation in larger samples. FAU - Dubin, Marc J AU - Dubin MJ AD - 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). FAU - Mao, Xiangling AU - Mao X AD - 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). FAU - Banerjee, Samprit AU - Banerjee S AD - 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). FAU - Goodman, Zachary AU - Goodman Z AD - 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). FAU - Lapidus, Kyle A B AU - Lapidus KA AD - 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). FAU - Kang, Guoxin AU - Kang G AD - 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). FAU - Liston, Conor AU - Liston C AD - 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). FAU - Shungu, Dikoma C AU - Shungu DC AD - 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). LA - eng GR - R01 MH100005/MH/NIMH NIH HHS/United States GR - R01 MH075895/MH/NIMH NIH HHS/United States GR - S10 OD021782/OD/NIH HHS/United States GR - R00 MH097822/MH/NIMH NIH HHS/United States GR - UL1 TR002384/TR/NCATS NIH HHS/United States GR - K99 MH097822/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - Canada TA - J Psychiatry Neurosci JT - Journal of psychiatry & neuroscience : JPN JID - 9107859 RN - 0RH81L854J (Glutamine) RN - 3KX376GY7L (Glutamic Acid) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Adult MH - Aged MH - Depressive Disorder, Major/diagnostic imaging/*metabolism/*therapy MH - Female MH - Glutamic Acid/metabolism MH - Glutamine/metabolism MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Prefrontal Cortex/diagnostic imaging/*metabolism MH - Proton Magnetic Resonance Spectroscopy MH - Psychiatric Status Rating Scales MH - *Transcranial Magnetic Stimulation MH - Treatment Outcome MH - Young Adult MH - gamma-Aminobutyric Acid/*metabolism PMC - PMC4853214 EDAT- 2016/02/24 06:00 MHDA- 2018/01/05 06:00 PMCR- 2016/05/01 CRDT- 2016/02/23 06:00 PHST- 2016/02/23 06:00 [entrez] PHST- 2016/02/24 06:00 [pubmed] PHST- 2018/01/05 06:00 [medline] PHST- 2016/05/01 00:00 [pmc-release] AID - 10.1503/jpn.150223 [pii] AID - jpn-41-e37 [pii] AID - 10.1503/jpn.150223 [doi] PST - ppublish SO - J Psychiatry Neurosci. 2016 Apr;41(3):E37-45. doi: 10.1503/jpn.150223.