Glutamate role in schizophrenia likely
medwireNews: The possible role of glutamate in schizophrenia is strengthened by a study showing normalized levels after successful antipsychotic treatment in patients with first-episode psychosis.
Proton magnetic resonance spectroscopy revealed baseline glutamate levels in the right associative striatum that averaged 31.34 Institutional Units (IU) in 24 patients with first-episode psychosis. As anticipated, this was significantly higher than in 18 mentally healthy controls, at 28.23 IU.
During 4 weeks of treatment, the patients’ average Positive and Negative Syndrome Scale (PANSS) scores fell significantly, from 94.5 to 58.7, and their glutamate levels followed suit, falling to 29.25 IU, whereas levels in controls remained stable at 27.97 IU.
Changes in glutamate levels in the patients significantly correlated with changes in the PANSS general psychopathology subscale.
These findings are in line with the theory that schizophrenia arises from neurodevelopmental abnormalities that lead to disturbed glutamatergic neurotransmission. In this case, say study author Ariel Graff-Guerrero (University of Toronto, Ontario, Canada) and team: “The deteriorating course of the disease may be partially explained by cortical neuronal toxic effects secondary to enhanced glutamatergic exposure, and dopaminergic dysregulation may be the final common pathway that results from altered glutamatergic neurotransmission.”
The researchers also assessed patients’ glutamate levels in the right cerebellar cortex because, unlike the dopamine-rich striatum, it has few dopamine receptors and no dopamine afferents. At baseline, patients had slightly but significantly higher levels than controls, at 24.46 versus 22.24 IU. Treatment had no effect on these values, with levels in both groups rising slightly to a respective 25.19 and 23.88 IU, which erased the significant difference between them.
Writing in JAMA Psychiatry, the team says it is “tempting to speculate” that the differences in glutamate changes observed could be “related to dopaminergic tone,” but cautions that the findings do not directly address this.
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By Eleanor McDermid, Senior medwireNews Reporter