title: Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum.
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.
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Roalf
authors.affiliation: Department of Radiology &Center for Magnetic and Optical Imaging, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R P R
authors.initials: RPR
authors.lastname: Nanga
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Rupert
authors.affiliation: Department of Radiology &Center for Magnetic and Optical Imaging, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hariharan
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Quarmley
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Dress
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Prabhakaran
authors.affiliation: Department of Radiology &Center for Magnetic and Optical Imaging, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Elliott
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Moberg
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: Department of Radiology &Center for Magnetic and Optical Imaging, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Reddy
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: B I
authors.initials: BI
authors.lastname: Turetsky
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D018698:Glutamic Acid / Q000032:analysis*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011618:Psychotic Disorders / Q000000981:diagnostic imaging*; D012307:Risk Factors; D012559:Schizophrenia
chemical_list: D018698:Glutamic Acid