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Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.

Publication ,  Journal Article
Kegeles, LS; Mao, X; Stanford, AD; Girgis, R; Ojeil, N; Xu, X; Gil, R; Slifstein, M; Abi-Dargham, A; Lisanby, SH; Shungu, DC
Published in: Arch Gen Psychiatry
May 2012

CONTEXT: 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. DESIGN: Case-control study. SETTING: Inpatient psychiatric research unit and associated outpatient clinic. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.

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Published In

Arch Gen Psychiatry

DOI

EISSN

1538-3636

Publication Date

May 2012

Volume

69

Issue

5

Start / End Page

449 / 459

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Schizophrenia
  • Psychiatry
  • Prefrontal Cortex
  • Neuroimaging
  • Memory, Short-Term
  • Male
  • Magnetic Resonance Spectroscopy
  • Magnetic Resonance Imaging
  • Humans
 

Citation

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Kegeles, L. S., Mao, X., Stanford, A. D., Girgis, R., Ojeil, N., Xu, X., … Shungu, D. C. (2012). Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry, 69(5), 449–459. https://doi.org/10.1001/archgenpsychiatry.2011.1519
Kegeles, Lawrence S., Xiangling Mao, Arielle D. Stanford, Ragy Girgis, Najate Ojeil, Xiaoyan Xu, Roberto Gil, et al. “Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.Arch Gen Psychiatry 69, no. 5 (May 2012): 449–59. https://doi.org/10.1001/archgenpsychiatry.2011.1519.
Kegeles LS, Mao X, Stanford AD, Girgis R, Ojeil N, Xu X, et al. Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2012 May;69(5):449–59.
Kegeles, Lawrence S., et al. “Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.Arch Gen Psychiatry, vol. 69, no. 5, May 2012, pp. 449–59. Pubmed, doi:10.1001/archgenpsychiatry.2011.1519.
Kegeles LS, Mao X, Stanford AD, Girgis R, Ojeil N, Xu X, Gil R, Slifstein M, Abi-Dargham A, Lisanby SH, Shungu DC. Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 2012 May;69(5):449–459.

Published In

Arch Gen Psychiatry

DOI

EISSN

1538-3636

Publication Date

May 2012

Volume

69

Issue

5

Start / End Page

449 / 459

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Schizophrenia
  • Psychiatry
  • Prefrontal Cortex
  • Neuroimaging
  • Memory, Short-Term
  • Male
  • Magnetic Resonance Spectroscopy
  • Magnetic Resonance Imaging
  • Humans