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.
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Acknowledgements
We thank the volunteers, especially the participants with schizophrenia, for participating in the study. This work is supported by National Institutes of Health (T32MH067533, R01MH094520, R01MH085646, R01DA027680, and P50MH103222). We thank Dr. Richard Edden and colleagues who kindly provided GANNET funded through NIH R01 EB016089 and P41 EB015909. We kindly thank Drs. William Carpenter and Juan Bustillo for their comments on this manuscript.
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Rowland, L., Krause, B., Wijtenburg, S. et al. Medial frontal GABA is lower in older schizophrenia: a MEGA-PRESS with macromolecule suppression study. Mol Psychiatry 21, 198–204 (2016). https://doi.org/10.1038/mp.2015.34
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DOI: https://doi.org/10.1038/mp.2015.34
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