Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy.

TitleElevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy.
Publication TypeJournal Article
Year of Publication2016
AuthorsDubin MJ, Mao X, Banerjee S, Goodman Z, Lapidus KAB, Kang G, Liston C, Shungu DC
JournalJ Psychiatry Neurosci
Date Published2016 04
KeywordsAdult, Aged, Depressive Disorder, Major, Female, gamma-Aminobutyric Acid, Glutamic Acid, Glutamine, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prefrontal Cortex, Proton Magnetic Resonance Spectroscopy, Psychiatric Status Rating Scales, Transcranial Magnetic Stimulation, Treatment Outcome, Young Adult

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) 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).

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.

Alternate JournalJ Psychiatry Neurosci
PubMed ID26900793
PubMed Central IDPMC4853214
Grant ListK99 MH097822 / MH / NIMH NIH HHS / United States
R00 MH097822 / MH / NIMH NIH HHS / United States
S10 OD021782 / OD / NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States