Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder.
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.
Price
Rebecca B
RB
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Shungu
Dikoma C
DC
Mao
Xiangling
X
Nestadt
Paul
P
Kelly
Chris
C
Collins
Katherine A
KA
Murrough
James W
JW
Charney
Dennis S
DS
Mathew
Sanjay J
SJ
D000328:Adult; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009778:Occipital Lobe / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid