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Transition to Psychosis Associated With Prefrontal and Subcortical Dysfunction in Ultra High-Risk Individuals
Authors:Paul Allen  Judy Luigjes  Oliver D Howes  Alice Egerton  Kazuyuki Hirao  Isabel Valli  Joseph Kambeitz  Paolo Fusar-Poli  Matthew Broome  Philip McGuire
Institution:1.Department of Psychosis Studies, Institute of Psychiatry, King''s College, London, UK;2.Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;3.Department of Neuropsychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan;4.Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy;5.Health Sciences Research Institute, University of Warwick, Coventry, UK
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.
Keywords:prodromal psychosis  schizophrenia  prefrontal cortex  dopamine  MRI  18F-DOPA PET
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