A variant in the COMT gene and psychosis in youth who have used cannabis

Abstract

Cannabis use is a known risk factor for the development of psychotic disorders. Clinical and preclinical genetic studies provide growing evidence that genes related to dopamine signalling and neuroprotection, like COMT, are implicated in the cannabis-psychosis association. Considering the burden of psychosis on society, as well as increasing use of cannabis among the teenage population due to perceived safety regarding its use, it is of considerable current interest to determine some of the reasons why some teens who do use cannabis frequently grow up into adults unaffected by psychosis while others do not. Using TaqMan genotyping technology, the role of the COMT marker rs4680 (Val158Met) and cannabis use was explored in the development of psychosis in a sample of 231 patients recruited in Edmonton and Halifax, Canada. Data on cannabis use and other relevant variables were collected. Using Cox-regression survival analysis it was determined that cannabis use commencing during teenage years was associated with an earlier age of onset of psychosis in adulthood. Stratifying by users versus non-users of cannabis during adolescence, a Cox-regression survival analysis using COMT genotype as a factor showed that homozygous Val/Val COMT genotype was associated with earlier age of onset of psychosis in the presence of cannabis use under 20 years of age. The results are in line with previous study findings (Caspi et al., 2005; Decoster et al., 2011; Estrada et al., 2011) regarding cannabis use during the critical prefrontal cortex development period, and the interaction between cannabis and COMT.