TY - JOUR
T1 - The relationship between striatal dopamine and anterior cingulate glutamate in first episode psychosis changes with antipsychotic treatment
AU - Jauhar, Sameer
AU - McCutcheon, Robert A.
AU - Veronese, Mattia
AU - Borgan, Faith
AU - Nour, Matthew
AU - Rogdaki, Maria
AU - Pepper, Fiona
AU - Stone, James M.
AU - Egerton, Alice
AU - Vamvakas, George
AU - Turkheimer, Federico
AU - McGuire, Philip K.
AU - Howes, Oliver D.
N1 - Funding Information:
SJ, JMS, AE, FT, PM and ODH are supported by the National Institute for Health Research Biomedical Research Centre at South London, Maudsley National Health Service Foundation Trust, King’s College London, and SJ by a JMAS (John, Margaret, Alfred, and Stewart) Sim Fellowship from the Royal College of Physicians, Edinburgh. MV is supported by MIUR, Italian Ministry for Education, under the initiatives “Departments of Excellence” (Law 232/2016) and by Wellcome Trust Digital Award (no. 215747/Z/19/Z). RM’s work is funded by a Wellcome Trust Clinical Research Career Development (224625/Z/21/Z). FB became an employee at COMPASS Pathways plc after the completion of this work. This work is unrelated to COMPASS Pathways plc. For the purpose of open access, this paper has been published under the creative common licence (CC-BY). This study was funded by Medical Research Council-UK (MC_U120097115; MR/W005557/1 and MR/V013734/1), and Wellcome Trust (no. 094849/Z/10/Z) grants to ODH and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS/NIHR or the Department of Health. SJ has received honoraria for educational lectures given for Boehringer Ingelheim, Janssen, Sunovion, and King’s College London has received honoraria for lectures SJ has given for Lundbeck. RM has received speaker consultancy fees from Karuna, Janssen, Boehringer Ingelheim, and Otsuka, and is director of a company that hosts psychotropic prescribing decision tools. MV hold a patent application for the use of dopamine imaging as a prognostic tool in mental health (WO2021111116). FB reports no biomedical, financial interests or potential conflicts of interest. MN reports no biomedical, financial interests or potential conflicts of interest. MR reports no biomedical, financial interests or potential conflicts of interest. FP reports no biomedical, financial interests or potential conflicts of interest. In the last 3 years, JMS has been principal investigator or sub-investigator on studies sponsored by Takeda, Janssen, and Lundbeck Plc. AE reports no biomedical, financial interests or potential conflicts of interest. GV reports no biomedical, financial interests or potential conflicts of interest. FT reports no biomedical, financial interests or potential conflicts of interest. PKM reports no biomedical, financial interests or potential conflicts of interest. ODH is a part-time employee and stock holder of Lundbeck A/s. He has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Janssen, Lundbeck, Neurocrine, Otsuka, Sunovion, Recordati, Roche and Viatris/ Mylan. ODH has a patent for the use of dopaminergic imaging.
Funding Information:
The authors would like to thank all the patients and their family members who facilitated this research, as well as Drs Paul Morrison and Nikola Rahamann, the Early Intervention teams in South London and Maudsley NHS Foundation Trust (COAST, STEP, LEO and LEIS) and CNWL who facilitated recruitment to the study.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psychosis. Striatal dopamine synthesis capacity (Kicer) and anterior cingulate glutamate were measured using 18F-DOPA positron emission tomography and proton magnetic resonance spectroscopy respectively, before and after at least 5 weeks’ naturalistic antipsychotic treatment in people with first episode psychosis (n = 18) and matched healthy controls (n = 20). The relationship between both measures at baseline and follow-up, and the change in this relationship was analyzed using a mixed linear model. Neither anterior cingulate glutamate concentrations (p = 0.75) nor striatal Kicer (p = 0.79) showed significant change following antipsychotic treatment. The change in relationship between whole striatal Kicer and anterior cingulate glutamate, however, was statistically significant (p = 0.017). This was reflected in a significant difference in relationship between both measures for patients and controls at baseline (t = 2.1, p = 0.04), that was not present at follow-up (t = 0.06, p = 0.96). Although we did not find any effect of antipsychotic treatment on absolute measures of dopamine synthesis capacity and anterior cingulate glutamate, the relationship between anterior cingluate glutamate and striatal dopamine synthesis capacity did change, suggesting that antipsychotic treatment affects the relationship between glutamate and dopamine.
AB - The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psychosis. Striatal dopamine synthesis capacity (Kicer) and anterior cingulate glutamate were measured using 18F-DOPA positron emission tomography and proton magnetic resonance spectroscopy respectively, before and after at least 5 weeks’ naturalistic antipsychotic treatment in people with first episode psychosis (n = 18) and matched healthy controls (n = 20). The relationship between both measures at baseline and follow-up, and the change in this relationship was analyzed using a mixed linear model. Neither anterior cingulate glutamate concentrations (p = 0.75) nor striatal Kicer (p = 0.79) showed significant change following antipsychotic treatment. The change in relationship between whole striatal Kicer and anterior cingulate glutamate, however, was statistically significant (p = 0.017). This was reflected in a significant difference in relationship between both measures for patients and controls at baseline (t = 2.1, p = 0.04), that was not present at follow-up (t = 0.06, p = 0.96). Although we did not find any effect of antipsychotic treatment on absolute measures of dopamine synthesis capacity and anterior cingulate glutamate, the relationship between anterior cingluate glutamate and striatal dopamine synthesis capacity did change, suggesting that antipsychotic treatment affects the relationship between glutamate and dopamine.
UR - https://www.scopus.com/pages/publications/85160613959
U2 - 10.1038/s41398-023-02479-2
DO - 10.1038/s41398-023-02479-2
M3 - Article
C2 - 37253720
AN - SCOPUS:85160613959
SN - 2158-3188
VL - 13
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 184
ER -