More evidence for glutamate dysregulation in schizophrenia

Published on January 15, 2014 at 9:14 AM · No Comments

By Eleanor McDermid, Senior medwireNews Reporter

Levels of glutamine, but not glutamate, are elevated in the dorsal anterior cingulate of patients with established schizophrenia, say researchers.

Most previous studies have measured combined levels of glutamine and glutamate, rather than assessing their levels individually, although one study that directly measured glutamate found increased levels in the associative striatum and cerebellum of first-episode psychosis patients.

“Glutamine is the principal metabolite of synaptic glutamate and increased presynaptic release of glutamate could result in greater concentrations of glutamine,” say lead researcher Juan Bustillo (University of New Mexico, Albuquerque) and co-workers.

Their findings therefore suggest “that a basal increased release of presynaptic glutamate remains despite treatment with antipsychotic agents,” they write in JAMA Psychiatry. This is in line with a model of altered glutamatergic neurotransmission caused by N-methyl-D-aspartic acid receptor (NMDAR) hypofunction.

For the study, 84 schizophrenia patients on stable medication underwent proton magnetic resonance spectroscopy, as did 81 mentally healthy controls matched for age, gender, ethnicity, and family socioeconomic status.

Schizophrenia patients had significantly larger glutamine levels in the dorsal anterior cingulate than controls after accounting for age and smoking status. Glutamine levels also increased with older age, and the effect was slightly, albeit not significantly, larger in the schizophrenia group, resulting in a larger increase over time versus controls (0.07 vs 0.05 mM/year).

The ratio of glutamine to glutamate followed a similar pattern to glutamine, but glutamate levels were no higher in patients than controls, and did not increase with age.

Glutamine levels rose significantly in line with the severity of positive schizophrenia symptoms, but were not related to negative symptoms or to the dose of antipsychotics patients were taking. The researchers note that the effect size of glutamine levels on positive symptoms was fairly small, but nonetheless supports the model of NMDAR hypofunction in schizophrenia.

“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,” say Bustillo et al.

Such research could help to identify “subgroups of persistently symptomatic” patients who might benefit from drugs targeting glutamatergic neurotransmission, they add.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

Read in | English | Español | Français | Deutsch | Português | Italiano | 日本語 | 한국어 | 简体中文 | 繁體中文 | Nederlands | Русский | Svenska | Polski
Comments
The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical.Net.
Post a new comment
Post
You might also like... ×
Novel drug target could lead to better antipsychotic medications