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Higher Brain Glutamate Levels May Act as Biomarker of Schizophrenia Severity
Higher brain glutamate levels appear to be a biomarker of illness severity in patients with schizophrenia, according to a participant-level mega-analysis of proton magnetic resonance spectroscopy data that probed associations between altered glutamatergic function and various clinical and demographic factors in patients.
The mega-analysis included data from 42 studies spanning 1251 patients with schizophrenia and 1197 healthy individuals. Researchers published their findings online ahead of print in JAMA Psychiatry.
“Overall, these results indicate that higher glutamate levels may be associated with greater illness severity,” researchers wrote, “but that glutamate levels may be reduced through effective antipsychotic treatment to below those observed in healthy volunteers.”
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The analysis found that medial frontal cortex glutamatergic metabolite levels were lower in patients than in healthy volunteers and, in patients, were negatively associated with antipsychotic dose. Reductions in glutamate levels that occurred with age in both patients and volunteers were not accelerated in patients.
The study also showed a correlation between higher glutamate levels in the medial frontal cortex and medial temporal lobe and more severe symptoms in patients with schizophrenia, researchers reported. These included more total, positive, and negative symptoms, worse Clinical Global Impression Scores, and a lower level of overall functioning.
“The finding of elevated glutamate levels in patients with more severe symptoms provides further support for the use of glutamatergic measures as a potential biomarker of illness severity, alongside other measures,” researchers concluded, “and the development of novel treatments that target brain glutamatergic function.”
—Jolynn Tumolo
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