20. ELUCIDATING THE LINK BETWEEN CANNABIS USE AND PSYCHOSIS: FROM THE EXPOSOME AND PHENOME TO THE EPIGENOME AND RECEPTOME

• Published in: Schizophrenia bulletin Vol. 45; no. Supplement_2; p. S121
• Main Author: Radhakrishnan, Rajiv
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 09.04.2019
• Subjects: Plenary/Symposia
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbz022.079

Abstract As the legalization of cannabis sweeps across the globe, there is an urgent need to further elucidate the relationship between cannabinoids and psychosis. Ongoing epidemiological, genetics, neurobiological and brain imaging studies have yielded new information pertaining to this link. In this symposium that brings together international researchers at the forefront of this question, we will provide an update about research on the link between cannabis exposure and psychosis, from four different perspectives, namely that of the exposome, phenome, epigenome, and receptome. The cannabis-psychosis exposome: The exposome represents the sum total of environmental (non-genetic) risk factors relevant to psychosis. Sinan Guloksuz will present new data from the EU-GEI cohort comparing individuals with psychosis-spectrum disorder, their siblings and healthy controls. The data demonstrates that cannabis use is associated with psychosis expression in both case-control and sib-control analyses; and early onset of cannabis use before age 16 moderated the association between regular cannabis use and psychosis in the sib-control sample. The cannabis-psychosis phenome: Whether cannabis use results in a specific phenotype of schizophrenia is not known. Deepak Cyril D’Souza will present new data from a prospective study characterizing consecutive cases n>50) of a cannabis-specific psychosis phenotype i.e. cannabinoid induced acute and persistent psychosis (CIAPP). CIAPP will be compared to hospitalized cases of psychosis unrelated to cannabis use and cannabis use disorder, and healthy controls using assessments of behavior, cognition and EEG measures of information processing (including neural noise). The cannabis-psychosis epigenome: Cannabis has been shown to have epigenetic effects, including effects of DNA methylation in preclinical studies. Marta Di Forti will present new data from the EU-GEI study showing that cannabis use among first-episode psychosis (FEP) results in DNA methylation changes at multiple loci across the epigenome and also at CpG sites previously associated with schizophrenia. The cannabis-psychosis receptome: The directionality of change in CB1 receptor availability in schizophrenia i.e. whether CB1 receptors are decreased or increased in schizophrenia, has been controversial. Oliver Howes will present new data on CB1 receptor availability in a large multi-modal imaging study of antipsychotic naïve/free first-episode psychosis (FEP) using [11C] MePPEP PET imaging and fMRI. The data shows that CB1 receptor availability is decreased in FEP compared to healthy controls and is linked to cortical activation during memory encoding. Robin Murray will serve as a discussant for the symposium, and will discuss the significance of these findings, the challenges facing the field in elucidating the link between cannabis and psychosis, and directions for future research.