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Publication Detail
A polygenic score indexing a DRD2-related co-expression network is associated with striatal dopamine function
  • Publication Type:
    Journal article
  • Authors:
    D'Ambrosio E, Pergola G, PardiƱas AF, Dahoun T, Veronese M, Sportelli L, Taurisano P, Griffiths K, Jauhar S, Rogdaki M, Bloomfield MAP, Froudist-Walsh S, Bonoldi I, Walters JTR, Blasi G, Bertolino A, Howes OD
  • Publisher:
    NATURE PORTFOLIO
  • Publication date:
    23/07/2022
  • Journal:
    Scientific Reports
  • Volume:
    12
  • Article number:
    12610
  • Medium:
    Electronic
  • Status:
    Published
  • Country:
    England
  • Print ISSN:
    2045-2322
  • PII:
    10.1038/s41598-022-16442-6
  • Language:
    English
  • Keywords:
    Genetics of the nervous system, Psychosis, Schizophrenia
  • Notes:
    This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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.
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