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Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo.
Sportelli, Leonardo; Eisenberg, Daniel P; Passiatore, Roberta; D'Ambrosio, Enrico; Antonucci, Linda A; Bettina, Jasmine S; Chen, Qiang; Goldman, Aaron L; Gregory, Michael D; Griffiths, Kira; Hyde, Thomas M; Kleinman, Joel E; Pardiñas, Antonio F; Parihar, Madhur; Popolizio, Teresa; Rampino, Antonio; Shin, Joo Heon; Veronese, Mattia; Ulrich, William S; Zink, Caroline F; Bertolino, Alessandro; Howes, Oliver D; Berman, Karen F; Weinberger, Daniel R; Pergola, Giulio.
Afiliação
  • Sportelli L; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Eisenberg DP; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
  • Passiatore R; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA.
  • D'Ambrosio E; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
  • Antonucci LA; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
  • Bettina JS; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.
  • Chen Q; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
  • Goldman AL; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA.
  • Gregory MD; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Griffiths K; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Hyde TM; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA.
  • Kleinman JE; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.
  • Pardiñas AF; Holmusk Technologies, New York, NY, USA.
  • Parihar M; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Popolizio T; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Rampino A; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Shin JH; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Veronese M; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ulrich WS; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
  • Zink CF; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Bertolino A; Radiology Department, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Howes OD; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
  • Berman KF; Azienda Ospedaliero Universitaria Consorziale Policlinico, Bari, Italy.
  • Weinberger DR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Pergola G; Department of Information Engineering, University of Padua, Padua, Italy.
Nat Commun ; 15(1): 3342, 2024 Apr 30.
Article em En | MEDLINE | ID: mdl-38688917
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esquizofrenia / Dopamina / Corpo Estriado Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esquizofrenia / Dopamina / Corpo Estriado Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos