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Mol Psychiatry. 2019 Oct;24(10):1502-1512. doi: 10.1038/s41380-018-0042-4. Epub 2018 Apr 20.

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

Author information

1
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
2
Early Intervention Psychosis Clinical Academic Group, South London & Maudsley NHS Trust, London, UK.
3
Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
4
Psychiatric Imaging Group MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK.
5
Institute of Clinical Sciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, W12 0NN, UK.
6
Fiona Pepper, Centre for Neuroimaging Sciences, King's College, London, UK.
7
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK. oliver.howes@kcl.ac.uk.
8
Psychiatric Imaging Group MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK. oliver.howes@kcl.ac.uk.
9
Institute of Clinical Sciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, W12 0NN, UK. oliver.howes@kcl.ac.uk.

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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