Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction.
BACKGROUND
Recent evidence documents that cannabis use by young people is a modest statistical risk factor for psychotic symptoms in adulthood, such as hallucinations and delusions, as well as clinically significant schizophrenia. The vast majority of cannabis users do not develop psychosis, however, prompting us to hypothesize that some people are genetically vulnerable to the deleterious effects of cannabis.


METHODS
In a longitudinal study of a representative birth cohort followed to adulthood, we tested why cannabis use is associated with the emergence of psychosis in a minority of users, but not in others.


RESULTS
A functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent cannabis use on developing adult psychosis. Carriers of the COMT valine158 allele were most likely to exhibit psychotic symptoms and to develop schizophreniform disorder if they used cannabis. Cannabis use had no such adverse influence on individuals with two copies of the methionine allele.


CONCLUSIONS
These findings provide evidence of a gene x environment interaction and suggest that a role of some susceptibility genes is to influence vulnerability to environmental pathogens.
Caspi
Avshalom
A
Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom.
Moffitt
Terrie E
TE
Cannon
Mary
M
McClay
Joseph
J
Murray
Robin
R
Harrington
HonaLee
H
Taylor
Alan
A
Arseneault
Louise
L
Williams
Ben
B
Braithwaite
Antony
A
Poulton
Richie
R
Craig
Ian W
IW
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000465:Algorithms; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D003702:Delusions / Q000453:epidemiology / Q000523:psychology; D004777:Environment; D005260:Female; D005838:Genotype; D006212:Hallucinations / Q000453:epidemiology / Q000523:psychology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008385:Marijuana Smoking / Q000523:psychology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D018570:Risk Assessment
D004247:DNA; D002394:Catechol O-Methyltransferase