@article{6d35f580f9d14ff5923923e692af7ed0,
title = "A polygenic score indexing a DRD2-related co-expression network is associated with striatal dopamine function",
abstract = "The D2 dopamine receptor (D2R) is the primary site of the therapeutic action of antipsychotics and is involved in essential brain functions relevant to schizophrenia, such as attention, memory, motivation, and emotion processing. Moreover, the gene coding for D2R (DRD2) has been associated with schizophrenia at a genome-wide level. Recent studies have shown that a polygenic co-expression index (PCI) predicting the brain-specific expression of a network of genes co-expressed with DRD2 was associated with response to antipsychotics, brain function during working memory in patients with schizophrenia, and with the modulation of prefrontal cortex activity after pharmacological stimulation of D2 receptors. We aimed to investigate the relationship between the DRD2 gene network and in vivo striatal dopaminergic function, which is a phenotype robustly associated with psychosis and schizophrenia. To this aim, a sample of 92 healthy subjects underwent 18F-DOPA PET and was genotyped for genetic variations indexing the co-expression of the DRD2-related genetic network in order to calculate the PCI for each subject. The PCI was significantly associated with whole striatal dopamine synthesis capacity (p = 0.038). Exploratory analyses on the striatal subdivisions revealed a numerically larger effect size of the PCI on dopamine function for the associative striatum, although this was not significantly different than effects in other sub-divisions. These results are in line with a possible relationship between the DRD2-related co-expression network and schizophrenia and extend it by identifying a potential mechanism involving the regulation of dopamine synthesis. Future studies are needed to clarify the molecular mechanisms implicated in this relationship.",
keywords = "dopamine, psychosis, schizophrenia, genetics, PET",
author = "Enrico D'Ambrosio and Giulio Pergola and Pardi{\~n}as, {Antonio F} and Tarik Dahoun and Mattia Veronese and Leonardo Sportelli and Paolo Taurisano and Kira Griffiths and Sameer Jauhar and Maria Rogdaki and Bloomfield, {Michael AP} and Sean Froudist-Walsh and Walters, {James TR} and Giuseppe Blasi and Alessandro Bertolino and Oliver Howes",
note = "Funding Information: This research was funded in whole, or in part, by the Wellcome Trust [Grant number 094849/Z/10/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. MV is supported by MIUR, Italian Ministry for Education, under the initiatives “Departments of Excellence” (Law 232/2016), by National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London and by the Wellcome Trust Innovator Award 215747/Z/19/Z. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. AFP was supported by an Academy of Medical Sciences “Springboard” award (SBF005\1083). JTRW is an investigator on a grant from Takeda Pharmaceuticals Ltd. to Cardiff University, for a project unrelated to the work presented here. KG is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley (SLaM) NHS Foundation Trust and King{\textquoteright}s College London. TD is supported by the NIHR. ODH is supported by Medical Research Council-UK (no. MC_U120097115) and Wellcome Trust (no. 094849/Z/10/Z). Funding Information: This research was funded in whole, or in part, by the Wellcome Trust [Grant number 094849/Z/10/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. MV is supported by MIUR, Italian Ministry for Education, under the initiatives “Departments of Excellence” (Law 232/2016), by National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London and by the Wellcome Trust Innovator Award 215747/Z/19/Z. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. AFP was supported by an Academy of Medical Sciences “Springboard” award (SBF005\1083). JTRW is an investigator on a grant from Takeda Pharmaceuticals Ltd. to Cardiff University, for a project unrelated to the work presented here. KG is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley (SLaM) NHS Foundation Trust and King{\textquoteright}s College London. TD is supported by the NIHR. ODH is supported by Medical Research Council-UK (no. MC_U120097115) and Wellcome Trust (no. 094849/Z/10/Z). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jul,
day = "23",
doi = "10.1038/s41598-022-16442-6",
language = "English",
volume = "12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}