Abstract

Though the basic pathophysiology of psychosis is largely unknown, there is reliable evidence that genes contribute to its aetiology. Epidemiologic studies suggested that chronic use of cannabis is a risk factor for the development of psychosis. Recent researches have focused on the identification of genetic variants that moderate the effect of cannabis on psychosis occurrence.

We undertook a systematic review of primary studies that reported the direct measures of genetic risk in the association between cannabis use and psychosis considering cannabis use as an environmental factor under the gene-environment interaction model. The initial search from PubMed revealed 187 records, of which 113 were excluded on reading the abstract. Of 74 papers screened in full, 60 were reviews, 14 were included for data extraction.

We report a structured summary of populations studied, study design, evaluations of cannabis use, genetic variations, outcome measures and main results. The 14 primary studies included in the survey applied the candidate gene approach, COMT being the most investigated; also CNR1, BDNF and SLC6A4 were examined; a novel candidate gene, AKT1, was identified through a multistage approach.

Few candidate genes were investigated, and reliable replications were provided only for AKT1. Studies were heterogeneous in terms of experimental design and outcome measures, thus hampering an effective synthesis. We conclude that additional primary studies are warranted. An effort in harmonisation of data, coupled with the recent advances in genetic technologies, should be encouraged.

Keywords: Psychosis, schizophrenia, cannabis, genetic association, gene-environment interaction, polymorphisms.