Elevated Prefrontal Cortex {gamma}-Aminobutyric Acid and Glutamate-Glutamine Levels in Schizophrenia Measured In Vivo With Proton Magnetic Resonance Spectroscopy

JAMA Psychiatry, 05/11/2012

To the authors' knowledge, this study presents the first γ–aminobutyric acid (GABA) concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and glutamate–glutamine (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.

Methods

  • Case-control study.
  • Inpatient psychiatric research unit and associated outpatient clinic.
  • Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking.
  • 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.

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.

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