A gene polymorphism in cannabis consumers may increase risk of psychosis
April 10, 2005. Cannabis is the most widely used illicit drug in the world, but there is increasing evidence that its use during adolescence may increase the risk of developing psychosis later in life. Not all cannabis smokers develop psychotic symptoms, however, and it has been postulated that certain individuals may be genetically vulnerable to its effects.
Polymorphisms in several genes have been linked with schizophrenia. Given the likely role of dopaminergic dysfunction in the pathogenesis of psychosis, it is no surprise that most genetic investigations have focussed on variants in genes involved in dopamine neurotransmission. One such gene, COMT, is located on chromosome 22q11, a region highlighted in several genome scans of schizophrenia. COMT encodes catechol-O-methyltransferase, an enzyme involved in the metabolism of dopamine in the synapse. The COMT gene contains a common missense mutation that causes a valine to methionine substitution at codon 158, producing a less active enzyme. Genetic association studies suggest that the valine allele may increase the risk of developing schizophrenia, but as with cannabis smoking not all valine carriers become schizophrenic.
A study by Avshalom Caspi and colleagues at the Institute of Psychiatry in London provides evidence for a gene-environment interaction between COMT genotype and cannabis smoking. Their research, to be published in the journal Biological Psychiatry, investigated the COMT gene and adolescent cannabis smoking in a large longitudinal birth cohort study from Dunedin, New Zealand. Their data suggests that the COMT gene interacts with adolescent-onset cannabis use to predict the emergence of psychosis later in life. They found that carriers of the COMT valine allele were at an increased risk of psychotic symptoms in adulthood if they used cannabis as an adolescent.