Peripheral glutamate levels in schizophrenia: Evidence from a meta-analysis

Background: Recent research attempting to develop novel medications has turned to glutamatergic signaling pathways to find effective treatments for symptom clusters of schizophrenia. This meta-analysis was undertaken to clarify whether a difference in peripheral glutamate levels exists between patients with schizophrenia and healthy controls. Methods: The electronic databases Ovid MEDLINE, PubMed, and PsycINFO were systematically searched up to April 2013. The search was limited to case-control studies of blood glutamate levels in schizophrenia written in English. The differences in glutamate levels were evaluated by calculating standardized mean differences (SMD). Results: We found ten studies that met the inclusion criteria for a total of 320 schizophrenia patients and 294 controls. The meta-analysis showed that peripheral glutamate levels in schizophrenia patients were significantly higher overall than in controls (SMD = 0.635, p = 0.004). However, a significant effect of the method used to measure glutamate concentrations was found (F = 7.36, p = 0.01) where fluorometric assay was associated with effect sizes in the opposite direction. Conclusion: A higher blood glutamate concentration was found in patients with schizophrenia. However, given the small sample size and methodological differences among studies, this result is not conclusive. More comprehensive research is needed to understand the relationship between glutamate levels in schizophrenia in the blood and the brain.