Schizophrenia-like cognitive, trait and DNA markers in regular cannabis users

Abstract

Rationale: Converging evidence suggests that cannabis use can induce psychosis and is a distinct risk factor for schizophrenia. Taken together with the effects of Tetrahydrocannabinol (THC) on neural systems, dopamine and endocannabinoids it is likely that cannabis use may also produce sub- clinical psychosis-linked changes in a much larger number of regular recreational users; observable in schizophrenia-sensitive assessments. Use of the drug by individuals with genetic risk factors for schizophrenia appears to magnify the chances of pathology, and so changes in recreational users with one or more of these genetic markers may be more evident or pronounced. Method: 50 cannabis users and 50 non cannabis users were assessed in each of two studies. Study one assessed selective attention in the Latent Inhibition (LI) and Kamin Blocking (KB) paradigms and examined schizophrenia-linked traits using the short form of the Schizotypal Personality Questionnaire (the SPQ-B; Raine and Benishay, 1995). Study two assessed executive control (using an Anti-Saccade Test), decision-making (using the Iowa Gambling Task), and selective/sustained attention and inhibitory control (Continuous Performance Test). Study two included additional personality measures to explore paranoia, emotional processing, ambivalence and impulsivity. Across both studies, the relative contribution of seven genetic risk markers in five candidate genes for schizophrenia (DAOA, COMT, NRG1, FAAH and CNR1) were assessed. Key Results: Cannabis use was associated with abolished latent inhibition and significantly riskier decision making, especially in those who used the drug more frequently. Cannabis users reported significantly higher scores for psychosis-linked personality traits and there was a dose-response effect with heavier users experiencing more of these schizotypal traits. Some key trends existed in the genotyping data for the cannabis group. The psychosis-risk C allele in the NRG1 gene was linked to higher SPQ-B scores and more errors on the AST; and was also associated with longer use of cannabis. Cannabis users without the protective three-way T-G-G haplotype COMT gene had higher scores for the SPQ-B disorganised thinking subscale than users with the protective haplotype. Discussion: The data in this thesis suggests that cannabis users are showing differences in brain inhibitory function and decision-making akin to previous research with schizophrenic patients, their first degree relatives and high schizotypy scorers. Exposure to THC may contribute to changes in individuals by pushing them further along a schizophrenia-spectrum resulting in the display of more psychotic-like traits and cognitive dysfunction at sub-clinical levels. These preliminary findings need expansion and replication, particularly with regards to the COMT three-way haplotype.