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

Sameer Jauhar; Mattia Veronese; Matthew Nour; Maria Rogdaki; Pamela Erika Hathway; Federico Edoardo Turkheimer; James Stone; Alice Egerton; Philip McGuire; Shitij Kapur; Oliver Howes

doi:10.1038/s41380-018-0042-4

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

Sameer Jauhar, Mattia Veronese, Matthew Nour, Maria Rogdaki, Pamela Erika Hathway, Federico Edoardo Turkheimer, James Stone, Alice Egerton, Philip McGuire, Shitij Kapur, Oliver Howes

University of Melbourne

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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.

Original language	English
Pages (from-to)	1502–1512
Journal	Molecular Psychiatry
Volume	24
Early online date	20 Apr 2018
DOIs	https://doi.org/10.1038/s41380-018-0042-4
Publication status	Published - 2019

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@article{98623d4315084d0f89249484233aafec,

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

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{\textquoteright}s d = 1.55, p = 0.01) and controls (Cohen{\textquoteright}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.",

author = "Sameer Jauhar and Mattia Veronese and Matthew Nour and Maria Rogdaki and Hathway, {Pamela Erika} and Turkheimer, {Federico Edoardo} and James Stone and Alice Egerton and Philip McGuire and Shitij Kapur and Oliver Howes",

year = "2019",

doi = "10.1038/s41380-018-0042-4",

language = "English",

volume = "24",

pages = "1502–1512",

journal = "Molecular Psychiatry",

issn = "1359-4184",

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TY - JOUR

T1 - Determinants of treatment response in first episode psychosis

T2 - an 18F-DOPA PET study

AU - Jauhar, Sameer

AU - Veronese, Mattia

AU - Nour, Matthew

AU - Rogdaki, Maria

AU - Hathway, Pamela Erika

AU - Turkheimer, Federico Edoardo

AU - Stone, James

AU - Egerton, Alice

AU - McGuire, Philip

AU - Kapur, Shitij

AU - Howes, Oliver

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1038/s41380-018-0042-4

DO - 10.1038/s41380-018-0042-4

M3 - Article

SN - 1359-4184

VL - 24

SP - 1502

EP - 1512

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

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

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