The Meaning of Glutamate and the Quest for Biomarkers in the Transition to Psychosis

The Bossong et al study titled “Association of Hippocampal Glutamate Levels With Adverse Outcomes in Individuals at Clinical High Risk for Psychosis” represents an important step forward in the study of glutamatergic abnormalities in the pathophysiology of psychotic disorders. To our knowledge, this is the largest study of in dividuals at clinical high risk to date to use proton magnetic resonance spectroscopy (1H-MRS) and document that those with higher hippocampal glutamate are more likely to transition to psychosis. The hippocampus was selected as the region of interest because hippocampal abnormalities prior to the onset of psychosis have been shown in previous studies that used a variety of measures (ie, hypermetabolism, increased perfusion, reduced gray matter, and altered activation). Increased glutamate, as suggested by theN-methyl-d-aspartate hypofunction model of psychosis, has been proposed as a plausible common mechanism underlying these other abnormalities because of the tight coupling between neuronal activation, metabolism, blood flood, and structural plasticity. Although a relatively large body of literature has documented increases in glutamate concentrations in schizophrenia (as has a more limited body of literature on glutamate concentrations in bipolar disorder), the specificity to psychotic illness and the association with common confounds (such as long-term disease course and medication effects) have not been completely elucidated. The fact that at-r...
Source: JAMA Psychiatry - Category: Psychiatry Source Type: research