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, 38 (6), 1268-76

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

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

Paul Allen et al. Schizophr Bull.

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.

Figures

Fig. 1.
Fig. 1.
Statistical Parametric Maps (SPMs) showing regions of greater activation during verbal fluency (easy + hard trials) in (A) ultra high risk (UHR) > controls, (B) subjects with UHR that did transfer into psychosis (UHR-t) > controls, and (C) UHR-t > subjects with UHR that did not transfer into psychosis (UHR-nt).
Fig. 2.
Fig. 2.
(A) Psychophysiological interaction (PPI) seed region in midbrain and statistical parametric map (SPM) of PPI group negative effect in subjects with ultra high risk (UHR) that did transfer into psychosis (UHR-t) > subjects with UHR that did not transfer into psychosis (UHR-nt) in prefrontal cortex (P < .05 cluster corrected) and plots showing significantly greater negative (word repetition > verbal fluency) PPI contrast estimates in UHR-t subjects in (B) left superior frontal gyrus, and (C) right middle frontal gyrus.
Fig. 3.
Fig. 3.
Mean brainstem [18F]-DOPA k i cer by group (error bars = 95% CI).

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