Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder.
| Publication Type | Academic Article |
| Authors | Price R, Shungu D, Mao X, Nestadt P, Kelly C, Collins K, Murrough J, Charney D, Mathew S |
| Journal | Biol Psychiatry |
| Volume | 65 |
| Issue | 9 |
| Pagination | 792-800 |
| Date Published | 12/05/2008 |
| ISSN | 1873-2402 |
| Keywords | Brain, Depressive Disorder, Major, Drug Resistance, Glutamic Acid, Glutamine, Magnetic Resonance Spectroscopy, Neurotransmitter Agents, gamma-Aminobutyric Acid |
| 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 |
| PubMed ID | 19058788 |
| PubMed Central ID | PMC2934870 |