title: Cognitive effects of the ANK3 risk variants in patients with bipolar disorder and healthy individuals.
abstract: BACKGROUND
  Genetic variants within the ankyrin 3 gene (ANK3) have been identified as a risk factor for bipolar disorder. ANK3 influences action potential generation by clustering sodium gated channels and plays an integral role in neurotransmission. Thus, this gene may influence cognition, a process compromised in bipolar disorder. We investigated whether genetic variants of ANK3 would be associated with an array of cognitive functions in patients with bipolar disorder and healthy individuals.
  
  
  METHODS
  In a sample of 49 patients with bipolar disorder and 633 healthy subjects, we examined possible effects of 2 risk variants within ANK3, rs10994336 and rs10761482, on 7 neurocognitive domains.
  
  
  RESULTS
  Compared to healthy subjects, patients with bipolar disorder demonstrated significantly poorer performance on most of the cognitive domains examined. The risk C-allele of rs10761482 was significantly associated with worse performance on verbal comprehension, logical memory and processing speed in patients. This allele was significantly associated with worse performance on executive function and visual memory in healthy individuals. No significant association was observed between rs10994336 and cognition either in patients or healthy individuals.
  
  
  CONCLUSIONS
  The sample size of patients with bipolar disorder was small, and most of the patients were on psychotropic medication.
  
  
  CONCLUSIONS
  These results indicate that a risk variant within ANK3 may have an impact on neurocognitive function, suggesting a mechanism by which ANK3 confers risk for bipolar disorder.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. Electronic address: hori@ncnp.go.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Teraishi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Daimei
authors.initials: D
authors.lastname: Sasayama
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuo
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Nagashima
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Ikki
authors.initials: I
authors.lastname: Ishida
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Norie
authors.initials: N
authors.lastname: Koga
authors.affiliation: National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000328:Adult; D017487:Ankyrins / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins
keywords: ANK3; Bipolar disorder; Cognitive function; Endophenotype; Genetics