Allelic variation in RGS4 impacts functional and structural connectivity in the human brain

Joshua W. Buckholtz, Andreas Meyer-Lindenberg, Robyn A. Honea, Richard E. Straub, Lukas Pezawas, Michael F. Egan, Radhakrishna Vakkalanka, Bhaskar Kolachana, Beth A. Verchinski, Steven Sust, Venkata S. Mattay, Daniel R. Weinberger, Joseph H. Callicott

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


Regulator of G-protein signaling 4 (RGS4) modulates postsynaptic signal transduction by affecting the kinetics of Gα-GTP binding. Linkage, association, and postmortem studies have implicated the gene encoding RGS4 (RGS4) as a schizophrenia susceptibility factor. Using a multimodal neuroimaging approach, we demonstrate that genetic variation in RGS4 is associated with functional activation and connectivity during working memory in the absence of overt behavioral differences, with regional gray and white matter volume and with gray matter structural connectivity in healthy human subjects. Specifically, variation at one RGS4 single nucleotide polymorphism that has been associated previously with psychosis (rs951436) impacts frontoparietal and frontotemporal blood oxygenation level-dependent response and network coupling during working memory and results in regionally specific reductions in gray and white matter structural volume in individuals carrying the A allele. These findings suggest mechanisms in brain for the association of RGS4 with risk for psychiatric illness.

Original languageEnglish (US)
Pages (from-to)1584-1593
Number of pages10
JournalJournal of Neuroscience
Issue number7
StatePublished - Feb 14 2007
Externally publishedYes


  • G-protein
  • Genetics
  • Human
  • Schizophrenia
  • VBM
  • fMRI

ASJC Scopus subject areas

  • General Neuroscience


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