title: SCN1A affects brain structure and the neural activity of the aging brain.
abstract: BACKGROUND
  The aging of the human brain is accompanied by changes in cortical structure as well as functional activity and variable degrees of cognitive decline. One-third of the observable inter-individual differences in cognitive decline are thought to be heritable. SCN1A encodes the sodium channel α subunit and is considered to be a susceptibility gene for several neurological disorders with prominent cognitive deficits. In a recent genome-wide association study the C allele of the SCN1A variant rs10930201 was observed to be significantly associated with poor short-term memory performance. rs10930201 was further observed to be related to differences in neural activity during a working memory task.
  
  
  METHODS
  The aim of the present study was to explore whether SCN1A modifies the vulnerability to aging processes of the human brain. Therefore we assessed the interacting effects of the SCN1A vulnerability allele rs10930201 and age in terms of brain activity and brain morphology in 62 healthy volunteers between 21 and 82 years of age.
  
  
  RESULTS
  In C allele carriers, activity in the right inferior frontal cortex and the posterior cingulate cortex increased with age. Moreover, exploratory analysis revealed regional effects of rs10930201 on brain structure, indicating reduced gray matter densities in the frontal and insular regions in the C allele carriers.
  
  
  CONCLUSIONS
  Collectively, the present results suggest that the SCN1A polymorphism has modulatory effects on brain morphology and vulnerability to age-related alterations in brain activity of cortical regions that subserve working memory.
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Heidelberg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Meier
authors.forename: Traute
authors.initials: T
authors.lastname: Demirakca
authors.forename: Wencke
authors.initials: W
authors.lastname: Brusniak
authors.forename: Isabella
authors.initials: I
authors.lastname: Wolf
authors.forename: Kristin
authors.initials: K
authors.lastname: Liebsch
authors.forename: Nuran
authors.initials: N
authors.lastname: Tunc-Skarka
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nieratschker
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.forename: Franziska
authors.initials: F
authors.lastname: Matthäus
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ende
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Carsten
authors.initials: C
authors.lastname: Diener
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D001921:Brain / Q000033:anatomy & histology* / Q000098:blood supply; D001931:Brain Mapping; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D010100:Oxygen