Title | Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Price RB, Shungu DC, Mao X, Nestadt P, Kelly C, Collins KA, Murrough JW, Charney DS, Mathew SJ |
Journal | Biol Psychiatry |
Volume | 65 |
Issue | 9 |
Pagination | 792-800 |
Date Published | 2009 May 01 |
ISSN | 1873-2402 |
Keywords | Adult, Brain, Case-Control Studies, Depressive Disorder, Major, Drug Resistance, Female, gamma-Aminobutyric Acid, Glutamic Acid, Glutamine, Gyrus Cinguli, Humans, Magnetic Resonance Spectroscopy, Male, Middle Aged, Neurotransmitter Agents, Occipital Lobe |
Abstract | BACKGROUND: Significant alterations in gamma-aminobutyric acid (GABA) and glutamate levels have been previously reported in major depressive disorder (MDD); however, no studies to date have investigated associations between these amino acid neurotransmitters and treatment resistance. METHODS: The objective of this study was to compare occipital cortex (OCC) and anterior cingulate cortex (ACC) GABA and glutamate+glutamine (Glx) levels measured by proton magnetic resonance spectroscopy ((1)H MRS) in 15 medication-free treatment-resistant depression (TRD) patients with those in 18 nontreatment-resistant MDD (nTRD) patients and 24 healthy volunteers (HVs). RESULTS: Levels of OCC GABA relative to voxel tissue water (W) were decreased in TRD patients compared with both HV (20.2% mean reduction; p = .001; Cohen's d = 1.3) and nTRD subjects (16.4% mean reduction; p = .007; Cohen's d = 1.4). There was a similar main effect of diagnosis for ACC GABA/W levels (p = .047; Cohen's d = .76) with TRD patients exhibiting reduced GABA in comparison with the other two groups (22.4% to 24.5% mean reductions). Group differences in Glx/W were not significant in either brain region. Only GABA results in OCC survived correction for multiple comparisons. CONCLUSIONS: Our findings corroborate previous reports of decreased GABA in MDD and provide initial evidence for a distinct neuronal amino acid profile in patients who have failed to respond to several standard antidepressants, possibly indicative of abnormal glutamate/glutamine/GABA cycling. Given interest in novel antidepressant mechanisms in TRD that selectively target amino acid neurotransmitter function, the translational relevance of these findings awaits further study. |
DOI | 10.1016/j.biopsych.2008.10.025 |
Alternate Journal | Biol Psychiatry |
PubMed ID | 19058788 |
PubMed Central ID | PMC2934870 |
Grant List | K23-MH-069656 / MH / NIMH NIH HHS / United States R01 MH075895 / MH / NIMH NIH HHS / United States K23 MH069656-05 / MH / NIMH NIH HHS / United States M01 RR000071 / RR / NCRR NIH HHS / United States R01-MH07895 / MH / NIMH NIH HHS / United States K23 MH069656 / MH / NIMH NIH HHS / United States M01-RR-00071 / RR / NCRR NIH HHS / United States |
Related Institute:
MRI Research Institute (MRIRI)