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Elevated glutamine related to severity of psychotic symptoms in schizophrenia

Increased levels of glutamine found in the anterior dorsal cingulate of patients with schizophrenia appear to be associated with the degree of psychotic symptoms in these patients, according to recent study data.

The cross-sectional study enrolled patients who underwent neuroimaging at the University of New Mexico Hospital or the Albuquerque VA Medical Center. Researchers included 84 patients with a diagnosis of schizophrenia according to the DSM-IV-TR, and 81 patients with no diagnosed psychiatric disorders. Magnetic resonance spectroscopy was performed on all patients, and an axial T-2 image was captured. The voxel for all scans primarily encompassed gray matter in the anterior cingulate using sagittal and reformatted coronal images.

The researchers used LCModel fitting to quantify localized spectra. They established simulated basis sets for sequence parameters, including the following metabolites: alanine, aspartate, creatine, phosphocreatine, gamma-aminobutyric acid, glutamine, glutamate, glycerophosphocholine, phosphocholine, myo-inositol, lactate, N-acetylaspartate, N-acetylaspartylglutamate, scyllo-inositol and guanidine.

All patients also were assessed for cognition and psychopathology using various scales.

The main outcomes were glutamine, glutamate and the glutamine-to-glutamate ratio, as well as symptoms and cognition.

The researchers found increased levels of glutamine in the schizophrenic group (P=.01) compared with controls, as well as an increase in the glutamine-to-glutamate ratio (P=.007) in the schizophrenic group. No significant increase in glutamate was seen in the schizophrenic group (P=.89). The schizophrenic group also had increased level of choline (P=.002). A correlation was seen between glutamine levels and severity of psychotic symptoms (P=.02).

The researchers noted that glutamine concentration is a reliable indicator of synaptic glutamatergic neurotransmission in schizophrenic patients.

“Ongoing longitudinal studies examining glutamine in the acute psychotic state and following antipsychotic treatment will further clarify the mechanism by which increased glutamatergic turnover contributes to the pathophysiology of psychosis,” the researchers wrote. “This line of translational investigation may identify subgroups of persistently symptomatic patients for whom drugs like metabotropic MGluR2-3 agonists may be particularly helpful.”

Disclosure: Bustillo is a member of the speakers’ bureau and received honoraria for advisory board consulting for Otsuka America Pharmaceutical Inc. All other researchers report no relevant financial disclosures.