Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis

Rebekka Lencer, Jeffrey R. Bishop, Margret S H Harris, James L. Reilly, Shitalben Patel, Rick Kittles, Konasale M. Prasad, Vishwajit L. Nimgaonkar, Matcheri S. Keshavan, John A. Sweeney

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Similar smooth pursuit eye tracking dysfunctions are present across psychotic disorders. They include pursuit initiation and maintenance deficits that implicate different functional brain systems. This candidate gene study examined psychosis-related genotypes regulating dopamine and glutamate neurotransmission in relation to these pursuit deficits. One hundred and thirty-eight untreated first-episode patients with a psychotic disorder were genotyped for four markers in DRD2 and four markers in GRM3. The magnitude of eye movement abnormality in patients was defined in relation to performance of matched healthy controls (N = 130). Eighty three patients were followed after 6 weeks of antipsychotic treatment. At baseline, patients with a -141C deletion in DRD2 rs1799732 had slower initiation eye velocity and longer pursuit latency than CC insertion carriers. Further, GRM3 rs274622-CC carriers had poorer pursuit maintenance than T-carriers. Antipsychotic treatment resulted in prolonged pursuit latency in DRD2 rs1799732-CC insertion carriers and a decline in pursuit maintenance in GRM3 rs6465084-GG carriers. The present study demonstrates for the first time that neurophysiological measures of motor and neurocognitive deficits in patients with psychotic disorders have different associations with genes regulating dopamine and glutamate systems, respectively. Alterations in striatal D2 receptor activity through the -141C Ins/Del polymorphism could contribute to pursuit initiation deficits in psychotic disorders. Alterations in GRM3 coding for the mGluR3 protein may impair pursuit maintenance by compromising higher perceptual and cognitive processes that depend on optimal glutamate signaling in corticocortical circuits. DRD2 and GRM3 genotypes also selectively modulated the severity of adverse motor and neurocognitive changes resulting from antipsychotic treatment.

Original languageEnglish (US)
Pages (from-to)345-355
Number of pages11
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
Volume264
Issue number4
DOIs
StatePublished - Jun 2014

Keywords

  • Antipsychotic treatment effects
  • DRD2 gene
  • Eye tracking dysfunction
  • GRM3 gene
  • Intermediate phenotype
  • Psychotic disorders
  • Smooth pursuit

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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    Lencer, R., Bishop, J. R., Harris, M. S. H., Reilly, J. L., Patel, S., Kittles, R., Prasad, K. M., Nimgaonkar, V. L., Keshavan, M. S., & Sweeney, J. A. (2014). Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis. European Archives of Psychiatry and Clinical Neuroscience, 264(4), 345-355. https://doi.org/10.1007/s00406-013-0464-6