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Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis

Molecular Psychiatry volume 16, pages 67–75 (2011)Cite this article

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Abstract

Schizophrenia is characterized by altered prefrontal activity and elevated striatal dopaminergic function. To investigate the relationship between these abnormalities in the prodromal phase of the illness, we combined functional Magnetic Resonance Imaging and 18F-Dopa Positron Emission Tomography. When performing a verbal fluency task, subjects with an At-Risk Mental State showed greater activation in the inferior frontal cortex than controls. Striatal dopamine function was greater in the At-Risk group than in controls. Within the At-Risk group, but not the control group, there was a direct correlation between the degree of left inferior frontal activation and the level of striatal dopamine function. Altered prefrontal activation in subjects with an At-Risk Mental State for psychosis is related to elevated striatal dopamine function. These changes reflect an increased vulnerability to psychosis and predate the first episode of frank psychosis.

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Acknowledgements

We acknowledge the contribution of the volunteers who participated in the study, the radiographers who assisted with the imaging, and clinical professionals at OASIS. The Medical Research Council, UK and Psychiatry Research Trust provided funding for this study. PFP takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have agreed to its submission in this form.

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Authors and Affiliations

  1. Department of Psychological Medicine, Neuroimaging Section, Institute of Psychiatry, King's College London, UK

    P Fusar-Poli, O D Howes, P Allen, M Broome, I Valli & P McGuire

  2. PET Psychiatry Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK

    O D Howes, M-C Asselin, A J Montgomery & P M Grasby

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  1. P Fusar-Poli
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  2. O D Howes
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Fusar-Poli, P., Howes, O., Allen, P. et al. Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis. Mol Psychiatry 16, 67–75 (2011). https://doi.org/10.1038/mp.2009.108

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