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    Determinants of treatment response in first-episode psychosis: an F-18-DOPA PET study

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    Author
    Jauhar, S; Veronese, M; Nour, MM; Rogdaki, M; Hathway, P; Turkheimer, FE; Stone, J; Egerton, A; McGuire, P; Kapur, S; ...
    Date
    2019-10-01
    Source Title
    Molecular Psychiatry
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Kapur, Shitij
    Affiliation
    Medicine Dentistry & Health Sciences
    Metadata
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    Document Type
    Journal Article
    Citations
    Jauhar, S., Veronese, M., Nour, M. M., Rogdaki, M., Hathway, P., Turkheimer, F. E., Stone, J., Egerton, A., McGuire, P., Kapur, S. & Howes, O. D. (2019). Determinants of treatment response in first-episode psychosis: an F-18-DOPA PET study. MOLECULAR PSYCHIATRY, 24 (10), pp.1502-1512. https://doi.org/10.1038/s41380-018-0042-4.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255045
    DOI
    10.1038/s41380-018-0042-4
    Abstract
    Psychotic illnesses show variable responses to treatment. Determining the neurobiology underlying this is important for precision medicine and the development of better treatments. It has been proposed that dopaminergic differences underlie variation in response, with striatal dopamine synthesis capacity (DSC) elevated in responders and unaltered in non-responders. We therefore aimed to test this in a prospective cohort, with a nested case-control comparison. 40 volunteers (26 patients with first-episode psychosis and 14 controls) received an 18F-DOPA Positron Emission Tomography scan to measure DSC (Kicer) prior to antipsychotic treatment. Clinical assessments (Positive and Negative Syndrome Scale, PANSS, and Global Assessment of Functioning, GAF) occurred at baseline and following antipsychotic treatment for a minimum of 4 weeks. Response was defined using improvement in PANSS Total score of >50%. Patients were followed up for at least 6 months, and remission criteria applied. There was a significant effect of group on Kicer in associative striatum (F(2, 37) = 7.9, p = 0.001). Kicer was significantly higher in responders compared with non-responders (Cohen's d = 1.55, p = 0.01) and controls (Cohen's d = 1.31, p = 0.02). Kicer showed significant positive correlations with improvements in PANSS-positive (r = 0.64, p < 0.01), PANSS negative (rho = 0.51, p = 0.01), and PANSS total (rho = 0.63, p < 0.01) ratings and a negative relationship with change in GAF (r = -0.55, p < 0.01). Clinical response is related to baseline striatal dopaminergic function. Differences in dopaminergic function between responders and non-responders are present at first episode of psychosis, consistent with dopaminergic and non-dopaminergic sub-types in psychosis, and potentially indicating a neurochemical basis to stratify psychosis.

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