title: Effect of DISC1 on the P300 waveform in psychosis.
abstract: BACKGROUND
  Abnormalities in the neurophysiological measures P300 amplitude and latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1 (DISC1) has been proposed as a promising susceptibility gene for schizophrenia, and a previous study has suggested that it is associated with P300 deficits in schizophrenia.
  
  
  METHODS
  We examined the role of variation in DISC1 polymorphisms on the P300 endophenotype in a large sample of patients with schizophrenia or psychotic bipolar disorder (n = 149), their unaffected relatives (n = 130), and unrelated healthy controls (n = 208) using linear regression and haplotype analysis.
  
  
  RESULTS
  Significant associations between P300 amplitude and latency and DISC1 polymorphisms/haplotypes were found. Those homozygous for the A allele of single-nucleotide polymorphism (SNP) rs821597 displayed significantly reduced P300 amplitudes in comparison with homozygous for the G allele (P = .009) and the heterozygous group (P = .018). Haplotype analysis showed a significant association for DISC1 haplotypes (rs3738401|rs6675281|rs821597|rs821616|rs967244|rs980989) and P300 latency. Haplotype GCGTCG and ACGTTT were associated with shorter latencies.
  
  
  CONCLUSIONS
  The P300 waveform appears to be modulated by variation in individual SNPs and haplotypes of DISC1. Because DISC1 is involved in neurodevelopment, one hypothesis is that disruption in neural connectivity impairs cognitive processes illustrated by P300 deficits observed in this sample.
authors: Department of Psychosis Studies, NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College Londonand The South London and Maudsley NHS Foundation Trust, London SE58AF, UK. madiha.1.shaikh@kcl.ac.uk
authors: Madiha
authors: M
authors: Shaikh
authors: Mei-Hua
authors: MH
authors: Hall
authors: Katja
authors: K
authors: Schulze
authors: Anirban
authors: A
authors: Dutt
authors: Kuang
authors: K
authors: Li
authors: Ian
authors: I
authors: Williams
authors: Muriel
authors: M
authors: Walshe
authors: Miguel
authors: M
authors: Constante
authors: Matthew
authors: M
authors: Broome
authors: Marco
authors: M
authors: Picchioni
authors: Timothea
authors: T
authors: Toulopoulou
authors: David
authors: D
authors: Collier
authors: Daniel
authors: D
authors: Stahl
authors: Fruhling
authors: F
authors: Rijsdijk
authors: John
authors: J
authors: Powell
authors: Robin M
authors: RM
authors: Murray
authors: Maria
authors: M
authors: Arranz
authors: Elvira
authors: E
authors: Bramon
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000503:physiopathology; D058256:Brain Waves / Q000235:genetics; D004569:Electroencephalography; D018913:Event-Related Potentials, P300 / Q000235:genetics / Q000502:physiology*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000503:physiopathology*; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D016037:Single-Blind Method
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins