title: Transition to psychosis associated with prefrontal and subcortical dysfunction in ultra high-risk individuals.
abstract: BACKGROUND
  People at ultra high risk (UHR) of psychosis have an elevated risk of developing a psychotic disorder, but it is difficult to predict which individuals will make a transition to frank illness. We investigated whether functional magnetic resonance imaging (fMRI) in conjunction with a phonological fluency task at presentation could distinguish subjects who subsequently developed psychosis from those who did not.
  
  
  METHODS
  Sixty-five subjects (41 with an UHR and 24 healthy controls) were assessed at clinical presentation using fMRI, in conjunction with a verbal fluency task. [18F]-DOPA positron emission tomography (PET) data were also available in a subgroup of 21 UHR and 14 healthy controls subjects. UHR subjects were followed clinically for at least 2 years.
  
  
  RESULTS
  Compared with UHR subjects who did not become psychotic, UHR subjects who subsequently developed psychosis showed increased activation in bilateral prefrontal cortex (PFC), brainstem (midbrain/basilar pons), the left hippocampus, and greater midbrain-PFC connectivity. Furthermore, exploratory analysis of [18F]-DOPA PET data showed that transition to psychosis was associated with elevated dopaminergic function in the brainstem region.
  
  
  CONCLUSIONS
  In people at high risk of psychosis, increased activation in a network of cortical and subcortical regions may predict the subsequent onset of illness. Functional neuroimaging, in conjunction with clinical assessment and other investigations, may facilitate the prediction of outcome in subjects who are vulnerable to psychosis.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College, London, UK. P.allen@kcl.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Allen
authors.forename: Judy
authors.initials: J
authors.lastname: Luigjes
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.forename: Alice
authors.initials: A
authors.lastname: Egerton
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirao
authors.forename: Isabel
authors.initials: I
authors.lastname: Valli
authors.forename: Joseph
authors.initials: J
authors.lastname: Kambeitz
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar-Poli
authors.forename: Matthew
authors.initials: M
authors.lastname: Broome
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005462:Fluorine Radioisotopes; D059907:Functional Neuroimaging / Q000379:methods; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000503:physiopathology; D011149:Pons / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D019275:Radiopharmaceuticals; D012306:Risk; D013068:Speech Production Measurement / Q000379:methods
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine