title: Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia.
abstract: BACKGROUND
  Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction and abnormalities at the nodes of Ranvier (NOR) interface where myelin and axons interact.
  
  
  OBJECTIVE
  To identify abnormalities in the expression of oligodendroglial genes and proteins that participate in the formation, maintenance, and integrity of the NOR in SZ.
  
  
  METHODS
  The messenger RNA (mRNA) expression levels of multiple NOR genes were quantified in 2 independent postmortem brain cohorts of individuals with SZ, and generalizability to protein expression was confirmed. The effect of the ANK3 genotype on the mRNA expression level was tested in postmortem human brain. Case-control analysis tested the association of the ANK3 genotype with SZ. The ANK3 genotype's influence on cognitive task performance and functional magnetic resonance imaging activation was tested in 2 independent cohorts of healthy individuals.
  
  
  METHODS
  Research hospital. Patients  Postmortem samples from patients with SZ and healthy controls were used for the brain expression study (n = 46) and the case-control analysis (n = 272). Healthy white men and women participated in the cognitive (n = 513) and neuroimaging (n = 52) studies.
  
  
  METHODS
  The mRNA and protein levels in postmortem brain samples, genetic association with schizophrenia, cognitive performance, and blood oxygenation level-dependent functional magnetic resonance imaging.
  
  
  RESULTS
  The mRNA expression of multiple NOR genes was decreased in schizophrenia. The ANK3 rs9804190 C allele was associated with lower ANK3 mRNA expression levels, higher risk for SZ in the case-control cohort, and poorer working memory and executive function performance and increased prefrontal activation during a working memory task in healthy individuals.
  
  
  CONCLUSIONS
  These results point to abnormalities in the expression of genes and protein associated with the integrity of the NOR and suggest them as substrates for the disconnectivity syndrome in SZ. The association of ANK3 with lower brain mRNA expression levels implicates a molecular mechanism for its genetic, clinical, and cognitive associations with SZ.
authors: Department of Psychiatry, The Mount Sinai School of Medicine, Bronx, NY 10468, USA.
authors: Panos
authors: P
authors: Roussos
authors: Pavel
authors: P
authors: Katsel
authors: Kenneth L
authors: KL
authors: Davis
authors: Panos
authors: P
authors: Bitsios
authors: Stella G
authors: SG
authors: Giakoumaki
authors: Jigar
authors: J
authors: Jogia
authors: Kinga
authors: K
authors: Rozsnyai
authors: David
authors: D
authors: Collier
authors: Sophia
authors: S
authors: Frangou
authors: Larry J
authors: LJ
authors: Siever
authors: Vahram
authors: V
authors: Haroutunian
mesh_terms: D000483:Alleles; D000818:Animals; D017487:Ankyrins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D056344:Executive Function; D005260:Female; D005838:Genotype; D006220:Haloperidol / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008570:Memory, Short-Term; D011110:Polymorphism, Genetic; D011901:Ranvier's Nodes / Q000235:genetics* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins; D006220:Haloperidol