Brain Metabolites Altered in First-Episode Psychosis

January 14, 2019

By Will Boggs MD

NEW YORK—Even in a first episode of psychosis (FEP), alterations in brain metabolite levels are associated with neurocognitive performance, according to findings from a 7-Tesla proton magnetic resonance spectroscopy (MRS) study.

"We were quite surprised by the reductions in N-acetyl aspartate (NAA), gamma-amino butyric acid (GABA), and glutamate in the FEP population, suggesting neuronal dysfunction or damage despite the relatively early stage of disease," Dr. Peter B. Barker from Johns Hopkins University School of Medicine, Baltimore, Maryland told Reuters Health by email.

MRS has been used extensively to study FEP and schizophrenia, but most earlier studies used lower magnetic field strengths of 1.5 or 3 T. Using MRS at 7 T allows the estimation of more compounds at higher precision.

Dr. Barker and colleagues used 7-T MRS to compare metabolite levels in five brain regions of key importance in psychosis and schizophrenia between 81 individuals with FEP and 91 healthy controls.

Within the anterior cingulate cortex (ACC), glutamate, NAA, GABA, and glutathione (GSH) levels were significantly lower in individuals with FEP than in healthy controls, according to the January 9th JAMA Psychiatry online report.

NAA levels were also significantly lower in FEP patients in the orbitofrontal region and thalamus, and GSH levels were significantly lower in FEP patients in the thalamus, compared with healthy controls.

Among individuals with FEP, composite cognitive score correlated significantly with NAA in the centrum semiovale (CSO); executive function score correlated with glutamate in the CSO and negatively with GABA in the thalamus; visual memory score correlated with glutamate and NAA in the CSO and glutamate in the dorsolateral prefrontal cortex (DLPFC); processing speed and attention/working memory scores correlated with NAA in the CSO; and verbal memory score correlated with glutamate and GSH in the ACC.

In contrast, regional metabolite levels correlated with few neuropsychological measures among healthy controls: GABA levels in the DLPFC correlated with composite cognitive score and with executive functioning, while GSH in the DLPFC negatively correlated with executive functioning.

"7-T MRS provides a non-invasive survey of brain metabolism that can be used to characterize neurochemical abnormalities associated with FEP," Dr. Barker concluded. "7-T MRS biomarkers have promise for use in treatment trials aimed at improving cognitive function."


JAMA Psychiatry 2019.

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