| Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder. | |
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MedLine Citation:
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PMID: 19058788 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Rebecca B Price; Dikoma C Shungu; Xiangling Mao; Paul Nestadt; Chris Kelly; Katherine A Collins; James W Murrough; Dennis S Charney; Sanjay J Mathew |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-12-05 |
Journal Detail:
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Title: Biological psychiatry Volume: 65 ISSN: 1873-2402 ISO Abbreviation: Biol. Psychiatry Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-07 Completed Date: 2009-06-29 Revised Date: 2010-09-09 |
Medline Journal Info:
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Nlm Unique ID: 0213264 Medline TA: Biol Psychiatry Country: United States |
Other Details:
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Languages: eng Pagination: 792-800 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029-6574, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Brain / metabolism* Case-Control Studies Depressive Disorder, Major / metabolism* Drug Resistance* Female Glutamic Acid / metabolism* Glutamine / metabolism* Gyrus Cinguli / metabolism Humans Magnetic Resonance Spectroscopy* Male Middle Aged Neurotransmitter Agents / metabolism* Occipital Lobe / metabolism gamma-Aminobutyric Acid / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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K23 MH069656-05/MH/NIMH NIH HHS; K23-MH-069656/MH/NIMH NIH HHS; M01-RR-00071/RR/NCRR NIH HHS; R01-MH07895/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Neurotransmitter Agents; 56-12-2/gamma-Aminobutyric Acid; 56-85-9/Glutamine; 56-86-0/Glutamic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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