Provenzano FA, Guo J, Wall MM, et al. - Researchers investigated individuals at clinical high risk (CHR) for psychosis for neuroimaging-derived hippocampal biomarkers to further define the pathophysiology of early psychosis. They hypothesized that in CHR individuals, glutamate hyperactivity, indicated by increased metabolic activity derived from functional MRI in the CA1 hippocampal subregion and from proton magnetic resonance spectroscopy–derived hippocampal levels of glutamate/glutamine, describes early hippocampal dysfunction and is predictive of conversion to syndromal psychosis. Three validated in vivo pathologies of hippocampal dysfunction—focal cerebral blood volume, focal atrophy, and evidence of elevated glutamate concentrations—were measured in 75 CHR individuals with attenuated positive symptom psychosis-risk syndrome using optimized MRI techniques. Outcomes yielded evidence that CHR patients with attenuated psychotic symptoms have glutamatergic abnormalities, although focal hippocampal atrophy was evident only in CHR patients who develop syndromal psychosis.