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The interaction between the ZNF804A gene and cannabis use on the risk of psychosis in a non‐clinical sample

Joaquim Soler, Bárbara Arias, Jorge Moya, M. Ibáñez, Generós Ortet, Lourdes Fañanás, Mar Fatjó‐Vilas

Progress in Neuro-Psychopharmacology and Biological Psychiatry March 1, 2019 DOI: 10.1016/j.pnpbp.2018.08.009 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 385
Population Spanish non-clinical subjects
Topics Cannabis
Key findings The AA genotype of ZNF804A rs1344706 was associated with higher interpersonal schizotypy scores and interacted with cannabis use to increase cognitive-perceptual schizotypy in a dose-dependent manner.

Abstract

ABSTRACT The ZNF804A gene and cannabis use are risk factors for psychosis and both have also been associated with schizotypal traits. This study aimed to investigate: i) the association of lifetime cannabis use (and its dose effect) with schizotypal personality traits, and ii) whether the genetic variability at ZNF804A gene modulates that association. Our sample consisted of 385 Spanish non‐clinical subjects (43.1% males, mean age=21.11(2.19)). Schizotypy was evaluated using the three factors of the Schizotypal Personality Questionnaire‐Brief (SPQ‐B): Cognitive‐Perceptual (SPQ‐CP), Interpersonal (SPQ‐I) and Disorganized (SPQ‐D). Subjects were classified according to their frequency of cannabis consumption, and dichotomized as users or non‐users. The effects of a genetic variant of ZNF804A (rs1344706) and cannabis use, as well as their interaction, on each of the three SPQ‐B factors were assessed using linear models and permutation tests. Sex, SCL anxiety scores and use of other drugs were included as covariates. Our analysis showed a significant relationship between ZNF804A and SPQ‐I: AA genotype was associated with higher scores (&bgr;=0.885 pFDR=.018). An interaction between the AA genotype and lifetime cannabis use was found in SPQ‐CP (&bgr;=1.297 pFDR=0.018). This interaction showed a dose–effect pattern among AA subjects: schizotypy scores increased with increasing frequency of cannabis use (sporadic users: &bgr;=0.746 pFDR=0.208; monthly users: &bgr;=1.688 pFDR=0.091; intense users: &bgr;=1.623 pFDR=0.038). These results add evidence on that the ZNF804A gene is associated with schizotypy and suggest that the interaction between cannabis use and ZNF804A genotype could modulate psychosis proneness. HIGHLIGHTSThe ZNF804A gene and cannabis use have been reported as risk factors for psychosis.We tested the effect of ZNF804A and cannabis on schizotypy in healthy subjects.We report the association of rs1344706 with interpersonal schizotypy.We found an rs1344706 x cannabis interaction affecting cognitive‐perceptual schizotypy.The effect of ZNF804A may be modulated by cannabis use and its intensity.

Comparable studies

Other observational and cohort studies on cannabis, most cited first.

Study Year Design Participants
High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population 2009 Case-control study n = 454
Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population 2013 Observational study
Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people 2000 Observational
Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline 2011 Observational cohort n = 1,923
Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... 2005 Observational cohort n = 535

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