Document Detail

Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder.
MedLine Citation:
PMID:  19058788     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-12-05
Journal Detail:
Title:  Biological psychiatry     Volume:  65     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-07     Completed Date:  2009-06-29     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  792-800     Citation Subset:  IM    
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
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MeSH Terms
Brain / metabolism*
Case-Control Studies
Depressive Disorder, Major / metabolism*
Drug Resistance*
Glutamic Acid / metabolism*
Glutamine / metabolism*
Gyrus Cinguli / metabolism
Magnetic Resonance Spectroscopy*
Middle Aged
Neurotransmitter Agents / metabolism*
Occipital Lobe / metabolism
gamma-Aminobutyric Acid / metabolism*
Grant Support
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
Reg. No./Substance:
0/Neurotransmitter Agents; 56-12-2/gamma-Aminobutyric Acid; 56-85-9/Glutamine; 56-86-0/Glutamic Acid

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