COMT Val(158)Met genotype and cannabis use in people with an At Risk Mental State for psychosis: Exploring Gene x Environment interactions

Dorien H. Nieman*, Sara Dragt, Esther D. A. van Duin, Nadine Denneman, Jozefien M. Overbeek, Lieuwe de Haan, Judith Rietdijk, Helga K. Ising, Rianne M. C. Klaassen, Therese van Amelsvoort, Lex Wunderink, Mark van der Gaag, Don H. Linszen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Web of Science)


Background: Epidemiological and retrospective studies suggest a cannabis x catechol-O-methyltransferase (COMT) Val(158)Met interaction effect on development of psychosis. The aim of this study was to examine this interaction and its association with severity of subclinical symptoms in people with an At Risk Mental State (ARMS) for psychosis. Methods: Severity of symptoms, cannabis use and genotype were assessed at baseline in 147 help-seeking young adults who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Results: Cannabis use and COMT Val-allele showed an interaction effect in ARMS subjects. Subjects who were weekly cannabis users at some point prior to entering the study showed more severe positive symptoms. This effect increased if they were carriers of the COMT Val-allele and even more so if they were homozygous for the Val-allele. Conclusions: Our results suggest that the COMT Val(158)Met polymorphism moderates the effect of regular cannabis use on severity of subclinical psychotic symptoms.
Original languageEnglish
Pages (from-to)24-28
JournalSchizophrenia Research
Issue number1-3
Publication statusPublished - Jul 2016


  • Psychosis
  • At Risk Mental State
  • COMT Val(158)Met
  • Cannabis
  • GxE interaction

Cite this