Transition to Psychosis Associated With Prefrontal and Subcortical Dysfunction in Ultra High-Risk Individuals

Paul Allen; Judy Luigies; Oliver Howes; Alice Egerton; Kasuyuki Hirao; Isabel Valli; Joseph Kambeitz; Paolo Fusar-Poli; Matthew Broome; Philip McGuire

doi:10.1093/schbul/sbr194

Transition to Psychosis Associated With Prefrontal and Subcortical Dysfunction in Ultra High-Risk Individuals

Paul Allen, Judy Luigies, Oliver Howes, Alice Egerton, Kasuyuki Hirao, Isabel Valli, Joseph Kambeitz, Paolo Fusar-Poli, Matthew Broome, Philip McGuire

Research output: Contribution to journal › Article

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.

Original language	English
Pages (from-to)	1268-1276
Journal	SCHIZOPHRENIA BULLETIN
Volume	38
Issue number	6
DOIs	https://doi.org/10.1093/schbul/sbr194
Publication status	Published - 2012

Access to Document

10.1093/schbul/sbr194

http://dx.doi.org/10.1093/schbul/sbr194

Cite this

@article{c8d0518c399d4979bbbea9a17eb65b19,

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.",

author = "Paul Allen and Judy Luigies and Oliver Howes and Alice Egerton and Kasuyuki Hirao and Isabel Valli and Joseph Kambeitz and Paolo Fusar-Poli and Matthew Broome and Philip McGuire",

year = "2012",

doi = "10.1093/schbul/sbr194",

language = "English",

volume = "38",

pages = "1268--1276",

journal = "SCHIZOPHRENIA BULLETIN",

issn = "0586-7614",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Transition to Psychosis Associated With Prefrontal and Subcortical Dysfunction in Ultra High-Risk Individuals

AU - Allen, Paul

AU - Luigies, Judy

AU - Howes, Oliver

AU - Egerton, Alice

AU - Hirao, Kasuyuki

AU - Valli, Isabel

AU - Kambeitz, Joseph

AU - Fusar-Poli, Paolo

AU - Broome, Matthew

AU - McGuire, Philip

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1093/schbul/sbr194

DO - 10.1093/schbul/sbr194

M3 - Article

SN - 0586-7614

VL - 38

SP - 1268

EP - 1276

JO - SCHIZOPHRENIA BULLETIN

JF - SCHIZOPHRENIA BULLETIN

IS - 6

ER -