Are there glutamate abnormalities in subjects at high risk mental state for psychosis? A review of the evidence

Abstract

New approaches to underlying alterations in psychosis suggest increasing evidence of glutamatergic abnormalities in schizophrenia and an association between these abnormalities and certain core psychopathological alterations such as cognitive impairment and negative symptoms. Proton magnetic resonance spectroscopy (1H MRS) is an MR-based technique that enables investigators to study glutamate function by measuring in vivo glutamatergic indices in the brain. In this article we review the published studies of 1H MRS in subjects with an at-risk mental state (ARMS) for psychosis. The primary aim was to investigate whether alterations in glutamate function are present before the illness develops in order to expand our understanding of glutamatergic abnormalities in prodromal phases. Three databases were consulted for this review. Titles and abstracts were examined to determine if they fulfilled the inclusion criteria. The reference lists of the included studies were also examined to identify additional trials. Eleven final studies were included in this review. Significant alterations in glutamate metabolites across different cerebral areas (frontal lobe, thalamus, and the associative striatum) in subjects with an ARMS for psychosis are reported in six of the trials. A longitudinal analysis in two of these trials confirmed an association between these abnormalities and worsening of symptoms and final transition to psychosis. Considering that five other studies found no significant differences across these same areas, we can conclude that more research is needed to confirm glutamatergic abnormalities in subjects with an ARMS for psychosis. However, future research must overcome the methodological limitations of existing studies to obtain reliable results.