Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.
BACKGROUND
Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness.


OBJECTIVE
To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls.


METHODS
Case-control study.


METHODS
Inpatient psychiatric research unit and associated outpatient clinic.


METHODS
Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking.


METHODS
Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects.


METHODS
The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy.


RESULTS
In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found.


CONCLUSIONS
To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. lsk5@columbia.edu
Lawrence S
LS
Kegeles
Xiangling
X
Mao
Arielle D
AD
Stanford
Ragy
R
Girgis
Najate
N
Ojeil
Xiaoyan
X
Xu
Roberto
R
Gil
Mark
M
Slifstein
Anissa
A
Abi-Dargham
Sarah H
SH
Lisanby
Dikoma C
DC
Shungu
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D018698:Glutamic Acid / Q000032:analysis*; D005973:Glutamine / Q000032:analysis*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008570:Memory, Short-Term; D059906:Neuroimaging; D017397:Prefrontal Cortex / Q000737:chemistry*; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid