Study Confirms AKT1 Genotype Contributes to Risk of Cannabis Psychosis

A genetic study led by Dr Marta Di Forti from the King’s College London’s Institute of Psychiatry has provided new evidence that genetic variation in the AKT1 gene – short for ‘V-akt murine thymoma viral oncogene homolog 1’ – influences the risk of developing psychosis in cannabis users.

Left: this drawing from Franz Eugen Köhler’s Medizinal-Pflantzen shows Cannabis sativa. Right: green arrow points to location of the AKT1 gene on the long arm of chromosome 14

The ability of cannabis to produce psychosis is an important public health concern. Some studies have suggested that cannabis exposure during adolescence may increase the risk of developing schizophrenia.

For these reasons, it would be valuable if a biological test could be developed that predicted the risk of developing psychosis in people who abuse cannabis or use marijuana as a medication.

A recent study has implicated a variation in the gene that codes for a protein called RAC-alpha serine/threonine-protein kinase in the risk for cannabis psychosis. However, independent verification of these finding is critical for genetic associations with complex genetic traits, like cannabis-related psychosis, because these findings are difficult to replicate.

Dr Forti’s team carried out a case control study to investigate variation in the AKT1 gene and cannabis use in increasing the risk of psychosis.

“We studied the AKT1 gene as this is involved in dopamine signaling which is known to be abnormal in psychosis. Our sample comprised 489 patients with their first episode of psychosis and 278 healthy controls,” explained Dr Forti, who, with colleagues, reports on the results in the journal Biological Psychiatry.

The team performed genotyping on all volunteers, and assessed their use of cannabis. “We found that cannabis users who carry a particular variant in the AKT1 gene (rs2494732) had a two-fold increased probability of a psychotic disorder and this increased up to seven-fold if they used cannabis daily,” the authors said. “Our findings help to explain why one cannabis user develops psychosis while his friends continue smoking without problems.”

“While the AKT1 genotype does not rise to the level of a clinically useful test of the risk for cannabis psychosis, it does show that this source of psychosis risk has a genetic underpinning,” said Dr John Krystal, Editor of Biological Psychiatry. “This advance also points to cellular signaling mechanisms mediated by Akt1 as being relevant to the biology of cannabis psychosis. This may suggest research directions for novel therapeutics for cannabis psychosis.”

“Such findings could also help to design health educational campaigns tailored to reach those young people at particular risk,” Di Forti added.

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Bibliographic information: Marta Di Forti et al. 2012. Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users. Biological Psychiatry, vol. 72, no. 10, 811-816; doi: 10.1016/j.biopsych.2012.06.020