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

Humans Dopamine / metabolism Schizophrenia / genetics Male Female Corpus Striatum / metabolism Adult Caudate Nucleus / metabolism Signal Transduction Middle Aged Hippocampus / metabolism Multifactorial Inheritance Genetic Predisposition to Disease Dorsolateral Prefrontal Cortex / metabolism Reward

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
30 Apr 2024

Historique:

received: 04 09 2023

accepted: 22 03 2024

medline: 1 5 2024

pubmed: 1 5 2024

entrez: 30 4 2024

Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-47456-5 PMID: 38688917

pubmed: 38688917

doi: 10.1038/s41467-024-47456-5

pii: 10.1038/s41467-024-47456-5

doi:

Substances chimiques

Dopamine VTD58H1Z2X

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

3342

Informations de copyright

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