title: Functional outcome in people at high risk for psychosis predicted by thalamic glutamate levels and prefronto-striatal activation.
abstract: Little is known about the neurobiological factors that determine functional outcome in people at high risk for psychosis. We use multimodal neuroimaging to investigate whether cortical responses during a cognitive task and thalamic glutamate levels were associated with subsequent functional outcome. Sixty subjects participated: 27 healthy controls (CTRL) and 33 at ultrahigh risk (UHR) for psychosis. At baseline, cortical responses during a verbal fluency task were measured using functional Magnetic Resonance Imaging (fMRI) and proton Magnetic Resonance Spectroscopy (1H-MRS) was used to measure thalamic glutamate levels. The UHR subjects were then followed clinically for a mean duration of 18 months, and subdivided into "good" and "poor" functional outcome subgroups according to their Global Assessment of Function score at follow-up. UHR subjects with a poor functional outcome showed greater cortical and subcortical activation than UHR subjects with a good functional outcome. They also had lower levels of thalamic glutamate and showed a negative relationship between thalamic glutamate levels and prefrontal-striatal activation that was not present in the good functional outcome or control groups. In people at high risk for psychosis, their subsequent level of functioning may depend on the extent to which neurophysiological and neurochemical function is perturbed when they first present to clinical services.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, Denmark Hill, 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, Denmark Hill, London, UK;
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Chaddock
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, Denmark Hill, London, UK;
authors.forename: Alice
authors.initials: A
authors.lastname: Egerton
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, Denmark Hill, London, UK;
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.affiliation: Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK;
authors.forename: Gareth
authors.initials: G
authors.lastname: Barker
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, Denmark Hill, London, UK; 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, Denmark Hill, London, UK;
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar-Poli
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, Denmark Hill, London, UK;
authors.forename: Robin
authors.initials: R
authors.lastname: Murray
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, Denmark Hill, London, UK;
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D064847:Multimodal Imaging; D017072:Neostriatum / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011618:Psychotic Disorders / Q000378:metabolism* / Q000503:physiopathology*; D012306:Risk; D013788:Thalamus / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018698:Glutamic Acid
keywords: functional MRI; functional outcomes; glutamate; psychosis; spectroscopy; ultra-high risk