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

Autor: Sportelli L; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy., Eisenberg DP; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA., Passiatore R; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy., D'Ambrosio E; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK., Antonucci LA; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy., Bettina JS; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA., Chen Q; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Goldman AL; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Gregory MD; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA., Griffiths K; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.; Holmusk Technologies, New York, NY, USA., Hyde TM; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Kleinman JE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Pardiñas AF; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK., Parihar M; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Popolizio T; Radiology Department, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy., Rampino A; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.; Azienda Ospedaliero Universitaria Consorziale Policlinico, Bari, Italy., Shin JH; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Veronese M; Department of Information Engineering, University of Padua, Padua, Italy.; Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK., Ulrich WS; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Zink CF; Baltimore Research and Education Foundation, Baltimore, MD, USA., Bertolino A; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.; Azienda Ospedaliero Universitaria Consorziale Policlinico, Bari, Italy., Howes OD; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK., Berman KF; Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA., Weinberger DR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA. Daniel.Weinberger@libd.org.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Daniel.Weinberger@libd.org.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Daniel.Weinberger@libd.org.; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Daniel.Weinberger@libd.org.; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Daniel.Weinberger@libd.org., Pergola G; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA. Giulio.Pergola@libd.org.; Group of Psychiatric Neuroscience, Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy. Giulio.Pergola@libd.org.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Giulio.Pergola@libd.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 30; Vol. 15 (1), pp. 3342. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1038/s41467-024-47456-5
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: