title: Relationship between brain glutamate levels and clinical outcome in individuals at ultra high risk of psychosis.
abstract: Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship to clinical outcome in at-risk individuals is unknown. Glutamate concentration was measured in the left thalamus and anterior cingulate cortex (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of attenuated positive symptoms and overall functioning were assessed. Measures were repeated in 51 UHR and 33 Control subjects after a mean of 18 months. UHR subjects were allocated to either remission (no longer meeting UHR criteria) or non-remission (meeting UHR or psychosis criteria) status on follow-up assessment. Thalamic glutamate levels at presentation were lower in the UHR non-remission (N=29) compared with the remission group (N=22) (t(49)=3.03; P=0.004), and were associated with an increase in the severity of total positive symptoms over time (r=-0.33; df=47; P=0.02), most notably abnormal thought content (r=-0.442; df=47; P=0.003). In the UHR group, ACC glutamate levels were lower at follow-up compared with baseline (F(80)=4.28; P=0.04). These findings suggest that measures of brain glutamate function may be useful as predictors of clinical outcome in individuals at high risk of psychosis.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Egerton
authors.affiliation: 1] Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK [2] Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Stone
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Chaddock
authors.affiliation: Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Gareth J
authors.identifier: 0000000252147421
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: 1] Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK [2] Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bonoldi
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Howard
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Merritt
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Allen
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors.forename: Mary A
authors.initials: MA
authors.lastname: McLean
authors.affiliation: Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lythgoe
authors.affiliation: 1] Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK [2] MR-Center, University Children's Hospital, Zurich, Switzerland.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: O'Gorman
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, UK.
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000378:metabolism*; D012306:Risk; D055815:Young Adult
chemical_list: D018698:Glutamic Acid