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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

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