Medial frontal GABA is lower in older schizophrenia: a MEGA-PRESS with macromolecule suppression study

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 wit...

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Bibliographic Details
Published in:	Molecular psychiatry Vol. 21; no. 2; pp. 198 - 204
Main Authors:	Rowland, L M, Krause, B W, Wijtenburg, S A, McMahon, R P, Chiappelli, J, Nugent, K L, Nisonger, S J, Korenic, S A, Kochunov, P, Hong, L E
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-02-2016 Nature Publishing Group
Subjects:	59/57 692/699/476/1799 Adult Age Age Factors Antipsychotics Behavioral Sciences Biological Psychology Brain research Butyric acid Case-Control Studies Cognition Disorders - pathology Cognitive ability Comparative analysis Consent Contamination Cortex (cingulate) Cortex (frontal) Diagnosis Female Frontal Lobe - pathology GABA gamma-Aminobutyric Acid - metabolism gamma-Aminobutyric Acid - physiology Genetic aspects Gyrus Cinguli - pathology Humans Hypotheses Magnetic Resonance Imaging - methods Magnetic resonance spectroscopy Magnetic Resonance Spectroscopy - methods Male Medicine Medicine & Public Health Memory Memory, Short-Term - physiology Mental disorders Middle Aged Neuropsychological Tests Neurosciences Neurotransmitters original-article Pathophysiology Patients Pharmacotherapy Physiological aspects Psychiatric research Psychiatry Psychopathology Psychotropic drugs Quality of Life Schizophrenia Schizophrenia - pathology Short term memory Spectrum analysis γ-Aminobutyric acid United States Baltimore County Maryland United States > US Maryland Baltimore Maryland
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1359-4184 1476-5578
DOI:	10.1038/mp.2015.34