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Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum

Molecular Psychiatry volume 22, pages 1298–1305 (2017)Cite this article

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Abstract

Psychosis commonly develops in adolescence or early adulthood. Youths at clinical high risk (CHR) for psychosis exhibit similar, subtle symptoms to those with schizophrenia (SZ). Malfunctioning neurotransmitter systems, such as glutamate, are implicated in the disease progression of psychosis. Yet, in vivo imaging techniques for measuring glutamate across the cortex are limited. Here, we use a novel 7 Tesla MRI glutamate imaging technique (GluCEST) to estimate changes in glutamate levels across cortical and subcortical regions in young healthy individuals and ones on the psychosis spectrum. Individuals on the psychosis spectrum (PS; n=19) and healthy young individuals (HC; n=17) underwent MRI imaging at 3 and 7 T. At 7 T, a single slice GluCEST technique was used to estimate in vivo glutamate. GluCEST contrast was compared within and across the subcortex, frontal, parietal and occipital lobes. Subcortical (χ2 (1)=4.65, P=0.031) and lobular (χ2 (1)=5.17, P=0.023) GluCEST contrast levels were lower in PS compared with HC. Abnormal GluCEST contrast levels were evident in both CHR (n=14) and SZ (n=5) subjects, and correlated differentially, across regions, with clinical symptoms. Our findings describe a pattern of abnormal brain neurochemistry early in the course of psychosis. Specifically, CHR and young SZ exhibit diffuse abnormalities in GluCEST contrast attributable to a major contribution from glutamate. We suggest that neurochemical profiles of GluCEST contrast across cortex and subcortex may be considered markers of early psychosis. GluCEST methodology thus shows promise to further elucidate the progression of the psychosis disease state.

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Acknowledgements

Thanks to the acquisition and recruitment team: Jacqueline Meeks, Jeff Valdez, Elliott Yodh, R. Sean Gallagher, Jason Blake, Prayosha Villa and Kevin Seelaus. This work was supported by National Institute of Mental Health R01MH099156 to BIT, K01MH102609 to DRR, P41 NIBIB EB015893 and R01 NINDS NS087516 to RR, and RC2 MH089983, P50 MH096891 & T32 MH019112 to REG. Additional support was provided by the Dowshen Program for Neuroscience at the University of Pennsylvania. The funding sources were not directly involved in study design, collection, data analysis or interpretation nor manuscript writing.

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  1. Department of Psychiatry, Neuropsychiatry Section, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, , PA, USA

    D R Roalf, P E Rupert, M Quarmley, M E Calkins, E Dress, K Prabhakaran, P J Moberg, R C Gur, R E Gur & B I Turetsky

  2. Department of Radiology & Center for Magnetic and Optical Imaging, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia,, PA, USA

    R P R Nanga, H Hariharan, M A Elliott & R Reddy

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Roalf, D., Nanga, R., Rupert, P. et al. Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum. Mol Psychiatry 22, 1298–1305 (2017). https://doi.org/10.1038/mp.2016.258

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