Genetic association of ErbB4 and human cortical GABA levels in vivo

Stefano Marenco, Matthew Geramita, Jan Willem van der Veen, Alan S. Barnett, Bhaskar Kolachana, Jun Shen, Daniel R. Weinberger, Amanda J. Law

Research output: Contribution to journalArticlepeer-review

Abstract

NRG1-ErbB4 signaling controls inhibitory circuit development in the mammalian cortex through ErbB4-dependent regulation of GABAergic interneuron connectivity. Common genetic variation in ErbB4 (rs7598440) has been associated with ErbB4 messenger RNA levels in the human cortex and risk for schizophrenia. Recent work demonstrates that Erbb4 is expressed exclusively on inhibitory interneurons, where its presence on parvalbumin-positive cells mediates the effects ofNRG1on inhibitory circuit formation in the cortex. We therefore hypothesized that genetic variation in ErbB4 at rs7598440 would impact indices of GABA concentration in the human cortex.Wetested this hypothesis in 116 healthy volunteers by measuring GABA and GLX (glutamate + glutamine) with proton magnetic resonance spectroscopy in the dorsal anterior cingulate gyrus. ErbB4 rs7598440 genotype significantly predicted cortical GABA concentration (p = 0.014), but not GLX (p = 0.51), with A allele carriers having higher GABA as predicted by the allelic impact on ErbB4 expression. These data establish an association of ErbB4 and GABA in human brain and have implications for understanding the pathogenesis of schizophrenia and other psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)11628-11632
Number of pages5
JournalJournal of Neuroscience
Volume31
Issue number32
DOIs
StatePublished - Aug 10 2011
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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