Association of Hippocampal Glutamate Levels With Adverse Outcomes in Individuals at Clinical High Risk for Psychosis

Matthijs G. Bossong, M. Antoniades, Matilda Azis, Carly Samson, Beverley Quinn, Ilaria Bonoldi, Gemma Modinos, J. Perez, Oliver Howes, James Stone, Paul Allen, Philip K. McGuire

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Preclinical and human data suggest that hippocampal dysfunction plays a critical role in the onset of psychosis. Hyperactivity in the hippocampus is thought to drive increased subcortical dopamine function through glutamatergic projections to the striatum. The aim of the present study was to examine the relationship between hippocampal glutamate levels in people at clinical high risk (CHR) for psychosis and their subsequent clinical outcomes. 3-Tesla proton magnetic resonance spectroscopy was used to measure the concentration of glutamate and other metabolites in the left hippocampus in 86 CHR subjects and 30 healthy controls. After scanning, the CHR subjects were followed for a mean of 18.5 months, and clinical outcomes were assessed in terms of transition to psychosis and the level of overall functioning. Compared to CHR subjects who did not become psychotic, CHR subjects who developed psychosis showed higher glutamate levels. CHR subjects who developed psychosis also had higher myo-inositol and creatine levels compared to both CHR subjects who did not become psychotic and to controls. CHR subjects with a poor functional outcome had higher glutamate levels than CHR subjects with a good functional outcome. These findings suggest that adverse clinical outcomes in people at CHR for psychosis are associated with increased hippocampal metabolite levels at baseline.

© 2019, American Medical Association. The attached document (embargoed until 14/11/2019) is an author produced version of a paper published in JAMA PSYCHIATRY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.
Original languageEnglish
Pages (from-to)199-207
Issue number2
Publication statusPublished - 14 Nov 2018

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