title: Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study.
abstract: Gene-environment interactions involving the catechol-O-methyltransferase Val(158)Met polymorphism (COMT(Val158Met)) have been implicated in the causation of psychosis. Evidence from general population studies suggests that Met/Met subjects are sensitive to stress, a trait associated with psychosis. We hypothesized that the Met allele would moderate the effects of stress on negative affect (NA) in controls, and on NA and psychosis in patients with a psychotic disorder. Thirty-one patients with a psychotic disorder and comorbid cannabis misuse and 25 healthy cannabis users were studied with the experience sampling method (ESM), a structured diary technique assessing current context and emotional and psychotic experiences in daily life. A significant interaction between COMT(Val158Met) genotype and ESM stress in the model of NA was found for patients (interaction chi(2) = 7.4, P = 0.02), but not for controls (interaction chi(2) = 3.8, P = 0.15). In the model of ESM psychosis, a significant interaction between COMT(Val158Met) genotype and ESM stress was also apparent (interaction chi(2) = 11.6, P < 0.01), with Met/Met patients showing the largest increase in psychotic experiences as well as NA in reaction to ESM stress. The findings suggest that the COMT(Val158Met) polymorphism moderates affective and psychotic responses to stress in patients with psychosis, providing evidence for gene-environment interaction mechanisms in the formation of psychotic symptoms.
authors.affiliation: University Psychiatric Center Katholieke Universiteit Leuven, Leuvensesteenweg, Kortenberg, Belgium.
authors.forename: Ruud
authors.initials: R
authors.lastname: van Winkel
authors.forename: Cécile
authors.initials: C
authors.lastname: Henquet
authors.forename: Araceli
authors.initials: A
authors.lastname: Rosa
authors.forename: Sergi
authors.initials: S
authors.lastname: Papiol
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fananás
authors.forename: Marc
authors.initials: M
authors.lastname: De Hert
authors.forename: Jozef
authors.initials: J
authors.lastname: Peuskens
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.forename: Inez
authors.initials: I
authors.lastname: Myin-Germeys
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000235:genetics / Q000523:psychology; D008715:Methionine / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics / Q000523:psychology; D014633:Valine / Q000235:genetics* / Q000378:metabolism
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine