title: Evidence that the COMTVal158Met polymorphism moderates subclinical psychotic and affective symptoms in unaffected first-degree relatives of patients with schizophrenia.
abstract: OBJECTIVE
  Psychotic patients with COMT(Val158Met) Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele.
  
  
  METHODS
  Unaffected relatives (n=38) were arranged in as many genetically related pairs as possible (n=26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score.
  
  
  RESULTS
  Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction chi(2)=3.78, p=0.05). Stratified analyses revealed that IUS-RUS total BPRS scores were significantly associated in the case of Met-sharing (B=0.57, 95% CI: 0.22-0.93, p=0.002), but were not when there was no Met-sharing.
  
  
  CONCLUSIONS
  These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis.
authors.affiliation: University Psychiatric Center, Katholieke Universiteit Leuven, Leuvensesteenweg 517, 3070 Kortenberg, Belgium. ruud.van.winkel@uc-kortenberg.be
authors.forename: Ruud
authors.initials: R
authors.lastname: van Winkel
authors.forename: Pilar
authors.initials: P
authors.lastname: Isusi
authors.forename: Paloma
authors.initials: P
authors.lastname: Galdos
authors.forename: Elena
authors.initials: E
authors.lastname: Echevarria
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Bilbao
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Martin-Pagola
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Sergi
authors.initials: S
authors.lastname: Papiol
authors.forename: Ron
authors.initials: R
authors.lastname: Mengelers
authors.forename: Lydia
authors.initials: L
authors.lastname: Krabbendam
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.forename: Inez
authors.initials: I
authors.lastname: Myin-Germeys
mesh_terms: D000328:Adult; D010054:Brief Psychiatric Rating Scale; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D014633:Valine / Q000235:genetics*
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine