title: The relationship between dopamine receptor D1 and cognitive performance.
abstract: BACKGROUND
  Cognitive impairment cuts across traditional diagnostic boundaries and is one of the most typical symptoms in various psychiatric and neurobiological disorders.
  
  
  OBJECTIVE
  The objective of this study was to examine the genetic association between 94 candidate genes, including receptors and enzymes that participate in neurotransmission, with measures of cognition.
  
  
  METHODS
  The Clinical Dementia Rating (CDR), a global measure of cognition, and genotypes derived from a custom array of 1,536 single-nucleotide polymorphisms (SNPs) in 94 genes were available for a large postmortem cohort of Caucasian cases with Alzheimer's disease (AD), schizophrenia and controls (n=727). A cohort of healthy young males (n=1,493) originating from the LOGOS project (Learning On Genetics Of Schizophrenia Spectrum) profiled across multiple cognitive domains was available for targeted SNP genotyping. Gene expression was quantified in the superior temporal gyrus of control samples (n=109). The regulatory effect on transcriptional activity was assessed using the luciferase reporter system.
  
  
  RESULTS
  The rs5326-A allele at the promoter region of dopamine receptor D1 (DRD1) locus was associated with: (i) poorer cognition (higher CDR) in the postmortem cohort (P=9.325×10(-4)); (ii) worse cognitive performance relevant to strategic planning in the LOGOS cohort (P=0.008); (iii) lower DRD1 gene expression in the superior temporal gyrus of controls (P=0.038); and (iv) decreased transcriptional activity in human neuroblastoma (SH-SY5Y) cells (P=0.026).
  
  
  CONCLUSIONS
  An interdisciplinary approach combining genetics with cognitive and molecular neuroscience provided a possible mechanistic link among DRD1 and alterations in cognitive performance.
authors.affiliation: Icahn School of Medicine at Mount Sinai , New York, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tsang
authors.affiliation: Department of Psychiatry, New York, NY, USA; Friedman Brain Institute, New York, NY, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Fullard
authors.affiliation: Department of Psychology, University of Crete , Rethymno, Crete, Greece.
authors.forename: Stella G
authors.initials: SG
authors.lastname: Giakoumaki
authors.affiliation: Department of Psychiatry , New York, NY, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Katsel
authors.affiliation: Department of Psychiatry , New York, NY, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Katsel
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai , Athens, Greece.
authors.forename: Vasiliki Eirini
authors.initials: VE
authors.lastname: Karagiorga
authors.affiliation: Department of Psychiatry, University of California , San Diego, CA, USA.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Greenwood
authors.affiliation: Department of Psychiatry, University of California, San Diego, CA, USA; VISN-22 Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Braff
authors.affiliation: Department of Psychiatry, New York, NY, USA; James J. Peters VA Medical Center, Mental Illness Research Education and Clinical Center (MIRECC), 130 West Kingsbridge Road, Bronx, NY, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece; Computational Medicine Laboratory, Institute of Computer Science at FORTH, Heraklion, Greece.
authors.forename: Panos
authors.initials: P
authors.lastname: Bitsios
authors.affiliation: Department of Psychiatry, New York, NY, USA; Friedman Brain Institute, New York, NY, USA; James J. Peters VA Medical Center, Mental Illness Research Education and Clinical Center (MIRECC), 130 West Kingsbridge Road, Bronx, NY, USA.
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.affiliation: Department of Psychiatry, New York, NY, USA; Friedman Brain Institute, New York, NY, USA; James J. Peters VA Medical Center, Mental Illness Research Education and Clinical Center (MIRECC), 130 West Kingsbridge Road, Bronx, NY, USA; Department of Genetics and Genomic Sciences, New York, NY, USA; Institute for Genomics and Multiscale Biology, New York, NY, USA.
authors.forename: Panos
authors.initials: P
authors.lastname: Roussos