Elevated gamma-aminobutyric acid levels in chronic schizophrenia.
BACKGROUND
Despite widely replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy control subjects in the anterior cingulate cortex and parieto-occipital cortex.


METHODS
Twenty-one schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy control subjects (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7-mL voxels and analyzed using LCModel.


RESULTS
We found elevations in GABA/creatine in the schizophrenia group compared with control subjects [F(1,65) = 4.149, p = .046] in both brain areas (15.5% elevation in anterior cingulate cortex, 11.9% in parieto-occipital cortex). We also found a positive correlation between GABA/creatine and glutamate/creatine, which was not accounted for by % GM or brain region.


CONCLUSIONS
We found elevated GABA/creatinine in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia.
Ongür
Dost
D
McLean Hospital, Belmont, Massachusetts 02478, USA. dongur@partners.org
Prescot
Andrew P
AP
McCarthy
Julie
J
Cohen
Bruce M
BM
Renshaw
Perry F
PF
D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D011522:Protons; D011877:Radionuclide Imaging; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011522:Protons; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine