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Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo

Author

Listed:
  • Leonardo Sportelli

    (Johns Hopkins Medical Campus
    University of Bari Aldo Moro)

  • Daniel P. Eisenberg

    (Intramural Research Program, NIH, DHHS)

  • Roberta Passiatore

    (University of Bari Aldo Moro)

  • Enrico D’Ambrosio

    (University of Bari Aldo Moro
    King’s College London)

  • Linda A. Antonucci

    (University of Bari Aldo Moro)

  • Jasmine S. Bettina

    (Intramural Research Program, NIH, DHHS)

  • Qiang Chen

    (Johns Hopkins Medical Campus)

  • Aaron L. Goldman

    (Johns Hopkins Medical Campus)

  • Michael D. Gregory

    (Intramural Research Program, NIH, DHHS)

  • Kira Griffiths

    (King’s College London
    Holmusk Technologies)

  • Thomas M. Hyde

    (Johns Hopkins Medical Campus
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Joel E. Kleinman

    (Johns Hopkins Medical Campus
    Johns Hopkins University School of Medicine)

  • Antonio F. Pardiñas

    (Cardiff University)

  • Madhur Parihar

    (Johns Hopkins Medical Campus)

  • Teresa Popolizio

    (IRCCS Ospedale Casa Sollievo della Sofferenza)

  • Antonio Rampino

    (University of Bari Aldo Moro
    Azienda Ospedaliero Universitaria Consorziale Policlinico)

  • Joo Heon Shin

    (Johns Hopkins Medical Campus)

  • Mattia Veronese

    (University of Padua
    King’s College London)

  • William S. Ulrich

    (Johns Hopkins Medical Campus)

  • Caroline F. Zink

    (Baltimore Research and Education Foundation)

  • Alessandro Bertolino

    (University of Bari Aldo Moro
    Azienda Ospedaliero Universitaria Consorziale Policlinico)

  • Oliver D. Howes

    (King’s College London)

  • Karen F. Berman

    (Intramural Research Program, NIH, DHHS)

  • Daniel R. Weinberger

    (Johns Hopkins Medical Campus
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Giulio Pergola

    (Johns Hopkins Medical Campus
    University of Bari Aldo Moro
    Johns Hopkins University School of Medicine)

Abstract

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia.

Suggested Citation

  • Leonardo Sportelli & Daniel P. Eisenberg & Roberta Passiatore & Enrico D’Ambrosio & Linda A. Antonucci & Jasmine S. Bettina & Qiang Chen & Aaron L. Goldman & Michael D. Gregory & Kira Griffiths & Thom, 2024. "Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47456-5
    DOI: 10.1038/s41467-024-47456-5
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    References listed on IDEAS

    as
    1. Urs Braun & Anais Harneit & Giulio Pergola & Tommaso Menara & Axel Schäfer & Richard F. Betzel & Zhenxiang Zang & Janina I. Schweiger & Xiaolong Zhang & Kristina Schwarz & Junfang Chen & Giuseppe Blas, 2021. "Brain network dynamics during working memory are modulated by dopamine and diminished in schizophrenia," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Alessandro Bertolino & Paolo Taurisano & Nicola Marco Pisciotta & Giuseppe Blasi & Leonardo Fazio & Raffaella Romano & Barbara Gelao & Luciana Lo Bianco & Madia Lozupone & Annabella Di Giorgio & Grazi, 2010. "Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance," PLOS ONE, Public Library of Science, vol. 5(2), pages 1-10, February.
    3. Wouter Saelens & Robrecht Cannoodt & Yvan Saeys, 2018. "A comprehensive evaluation of module detection methods for gene expression data," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Monkol Lek & Konrad J. Karczewski & Eric V. Minikel & Kaitlin E. Samocha & Eric Banks & Timothy Fennell & Anne H. O’Donnell-Luria & James S. Ware & Andrew J. Hill & Beryl B. Cummings & Taru Tukiainen , 2016. "Analysis of protein-coding genetic variation in 60,706 humans," Nature, Nature, vol. 536(7616), pages 285-291, August.
    5. Viechtbauer, Wolfgang, 2010. "Conducting Meta-Analyses in R with the metafor Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 36(i03).
    6. Vassily Trubetskoy & Antonio F. Pardiñas & Ting Qi & Georgia Panagiotaropoulou & Swapnil Awasthi & Tim B. Bigdeli & Julien Bryois & Chia-Yen Chen & Charlotte A. Dennison & Lynsey S. Hall & Max Lam & K, 2022. "Mapping genomic loci implicates genes and synaptic biology in schizophrenia," Nature, Nature, vol. 604(7906), pages 502-508, April.
    7. Alessandro Usiello & Ja-Hyun Baik & Françoise Rougé-Pont & Roberto Picetti & Andrée Dierich & Marianne LeMeur & Pier Vincenzo Piazza & Emiliana Borrelli, 2000. "Distinct functions of the two isoforms of dopamine D2 receptors," Nature, Nature, vol. 408(6809), pages 199-203, November.
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