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Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

Authors

  • Roscoe O Brady Jr,

    1. Department of Psychiatry, Beth-Israel Deaconess Hospital, Salt Lake City, UT, USA
    2. Department of Psychiatry, Harvard Medical School, Salt Lake City, UT, USA
    3. Department of Psychiatry, Massachusetts Mental Health Center, Boston, USA
    4. Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA
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    • These authors contributed equally to this manuscript.
  • Julie M McCarthy,

    1. Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA
    2. Department of Psychology, University of Maryland, College Park, MD, USA
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    • These authors contributed equally to this manuscript.
  • Andrew P Prescot,

    1. Department of Radiology, University of Utah School of Medicine, Salt Lake City, UT, USA
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  • J Eric Jensen,

    1. Department of Psychiatry, Harvard Medical School, Salt Lake City, UT, USA
    2. Brain Imaging Center, Salt Lake City, UT, USA
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  • Alissa J Cooper,

    1. Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA
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  • Bruce M Cohen,

    1. Department of Psychiatry, Harvard Medical School, Salt Lake City, UT, USA
    2. Shervert Frazier Research Institute, McLean Hospital, Belmont, MA, USA
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  • Perry F Renshaw,

    1. Brain Institute, University of Utah, Salt Lake City, UT, USA
    2. Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA
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  • Dost Öngür

    Corresponding author
    1. Department of Psychiatry, Harvard Medical School, Salt Lake City, UT, USA
    2. Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA
    3. Shervert Frazier Research Institute, McLean Hospital, Belmont, MA, USA
    • Department of Psychiatry, Beth-Israel Deaconess Hospital, Salt Lake City, UT, USA
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Corresponding author:

Dost Öngür, M.D., Ph.D.

Psychotic Disorders Division

Mclean Hospital

AB320

115 Mill Street

Belmont, MA 02478

USA

Fax: 617-855-2895

E-mail: dongur@partners.org

Abstract

Objectives

Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls.

Methods

Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel.

Results

GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications.

Conclusions

We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition.

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