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

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 (β = 0.885 p = .018). An interaction between the AA genotype and lifetime cannabis use was found in SPQ-CP (β = 1.297 p = 0.018). This interaction showed a dose-effect pattern among AA subjects: schizotypy scores increased with increasing frequency of cannabis use (sporadic users: β = 0.746 p = 0.208; monthly users: β = 1.688 p = 0.091; intense users: β = 1.623 p = 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.

Overlap between genetic variants associated with schizophrenia spectrum disorders and intelligence quotient: a systematic review

“…This polymorphism might be implicated specifically in SSD because it has been more frequently identified in patients with the disorder, 8,123,124 and it has been related to higher schizotypy scores in healthy individuals. 125 Overall, these findings agree on the value of the rs1344706 polymorphism as a potential genetic marker for risk of psychosis. The specific function of ZNF804A is still unknown, but it encodes a zinc finger binding protein, a type of protein that participates in diverse roles, such as binding to DNA, transcriptional regulation and DNA-protein interactions.…”

Association between Polymorphism rs1799732 of DRD2 Dopamine Receptor Gene and Personality Traits among Cannabis Dependency

“…This observation shows that there are two extremes of the personality characteristics which may be involved in CUD—on one side is the high neurotic predisposition and the other is schizothymic construct. Soler et al [ 51 ] proved that the cannabis-addicted patients with the genetic variant of ZNF804 (rs1344706) were characterized by their significant relationship with schizotypal personality traits and psychosis proneness. Furthermore, the schizotypy scores were positively correlated with the cannabis use pattern (dose and frequency) in these subjects.…”

Association between formal thought disorder and cannabis use: a systematic review and meta-analysis

“…In the various studies, FTD was referred to as "cognitive disorganization" 30,[37][38][39] , "disorganization" 23,[40][41][42][43][44][45] , "thought disturbance" 29 , "FTD" 46,47 or "positive FTD" 13,[48][49][50][51] . This is linked to the scale used (see supplementary material "Scales" for details).…”

“…For clarity, the umbrella term "FTD" will be used to refer to all these terms throughout this metaanalysis. Eight studies 23,30,[37][38][39]42,44,45 assessed FTD globally using two questionnaires, the Oxford-Liverpool Inventory of Feelings and Experiences 52 and the Schizotypal Personality Questionnaire 53 , as well as three scales: the Positive and Negative Syndrome Scale 54 , the Psychotomimetic States Inventory 52 , and the Structured Interview for Prodromal Symptoms 45 . Nine studies 13,29,40,41,46,[48][49][50][51] evaluated subcomponents of FTD using the Scale for the Assessment of Positive Symptoms 55 , the Brief Psychiatric Rating Scale 56 , the Young Mania Rating Scale 57 , the Operational Criteria for Psychotic Illness 58 and the Symptom Onset in Schizophrenia 59 .…”