title: Medial frontal GABA is lower in older schizophrenia: a MEGA-PRESS with macromolecule suppression study.
abstract: Gamma-butyric acid (GABA) dysfunction has been implicated in the pathophysiology of schizophrenia and its cognitive deficits. Proton magnetic resonance spectroscopy (MRS) was used to test the hypothesis that older participants with schizophrenia have lower anterior cingulate GABA levels compared with older control participants. One-hundred forty-five participants completed this study. For detection of GABA, spectra were acquired from the medial frontal/anterior cingulate cortex using a macromolecule-suppressed MEGA-PRESS sequence. Patients were evaluated for psychopathology and all participants completed neuropsychological tests of working memory, processing speed and functional capacity. GABA levels were significantly lower in the older participants with schizophrenia (n=31) compared with the older control (n=37) group (P=0.003) but not between the younger control (n=40) and schizophrenia (n=29) groups (P=0.994). Age strongly predicted GABA levels in the schizophrenia group accounting for 42% of the variance, but the effect of age was less in the control group accounting for 5.7% of the variance. GABA levels were specifically related to working memory but not processing speed performance, functional capacity, or positive or negative symptom severity. This is the largest MRS study of GABA in schizophrenia and the first to examine GABA without macromolecule contamination, a potentially significant issue in previous studies. GABA levels more rapidly declined with advancing age in the schizophrenia compared with the control group. Interventions targeted at halting the decline or increasing GABA levels may improve functional outcomes and quality of life as patients with schizophrenia age.
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Psychology, University of Maryland Baltimore County, Baltimore, MD, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Rowland
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Krause
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Wijtenburg
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: McMahon
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chiappelli
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Nugent
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Nisonger
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Korenic
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Physics, University of Maryland Baltimore County, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011788:Quality of Life; D012559:Schizophrenia / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000502:physiology*
chemical_list: D005680:gamma-Aminobutyric Acid
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