title: Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress.
abstract: OBJECTIVE
  A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined.
  
  
  METHODS
  A total of 98 patients with non-affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM).
  
  
  RESULTS
  The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P < 0.0001), but not in controls (P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ(2)(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ(2)(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found.
  
  
  CONCLUSIONS
  Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype.
authors: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, European Graduate School of Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University, The Netherlands.
authors: O
authors: O
authors: Peerbooms
authors: B P F
authors: BP
authors: Rutten
authors: D
authors: D
authors: Collip
authors: M
authors: M
authors: Lardinois
authors: T
authors: T
authors: Lataster
authors: V
authors: V
authors: Thewissen
authors: S Mafi
authors: SM
authors: Rad
authors: M
authors: M
authors: Drukker
authors: G
authors: G
authors: Kenis
authors: J
authors: J
authors: van Os
authors: I
authors: I
authors: Myin-Germeys
authors: R
authors: R
authors: van Winkel
mesh_terms: D000223:Adaptation, Psychological; D000328:Adult; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000235:genetics*; D055500:Resilience, Psychological; D013315:Stress, Psychological / Q000235:genetics*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002394:Catechol O-Methyltransferase