The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Abstract

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.

Beyond monoamines: II. Novel applications for PET imaging in psychiatric disorders

“…Evidence for the association between schizophrenia and the endocannabinoid system is drawn from observations that: (1) cannabis exposure is associated with acute psychoses (D'Souza et al, 2004; Ford et al, 2017; Murray et al, 2017; Wright et al, 2021), (2) the risk of schizophrenia and first‐episode psychoses is elevated in chronic cannabis abusers (Andréasson et al, 1987; Di Forti et al, 2019; Wainberg et al, 2021), (3) the risk of schizophrenia and first‐episode psychosis is linked with cannabis use and CaUD among those with certain polymorphisms (Johnson et al, 2021; Jones et al, 2020; Pasman et al, 2018; Quattrone et al, 2021), and (4) cannabis use by subjects with schizophrenia is associated with poorer outcomes and an exacerbation of disease symptoms (Athanassiou et al, 2021; Goldberger et al, 2010; Lev‐Ran et al, 2012; Sánchez‐Torres et al, 2013). Despite these compelling observations, a mechanistic explanation for the association between cannabis exposure and acute or worsening psychoses is lacking largely because of discordant findings both within and between postmortem, ex vivo, and in vitro studies of this association (Borgan et al, 2021) (Volk et al, 2014).…”

“…, (3) the risk of schizophrenia and first-episode psychosis is linked with cannabis use and CaUD among those with certain polymorphisms(Johnson et al, 2021;Jones et al, 2020;Pasman et al, 2018;Quattrone et al, 2021), and (4) cannabis use by subjects with schizophrenia is associated with poorer outcomes and an exacerbation of disease symptoms(Athanassiou et al, 2021;Goldberger et al, 2010;Lev-Ran et al, 2012;Sánchez-Torres et al, 2013). Despite these compelling observations, a mechanistic explanation for the association between cannabis exposure and acute or worsening psychoses is lacking largely because of discordant findings both within and between postmortem, ex vivo, and in vitro studies of this association(Borgan et al, 2021) (Volk et al, 2014).…”

Investigating environmental parameters involved in psychosis etiopathology. Translation and test-retest reliability of four scales

“…Schizophrenia-polygenic-score and cannabis use, independently from each other, are related to more severe positive symptomatology. 2,6,12 The goal of the current study, which is part of the Athens-FEP Study, is to present the Greek translation of TAQEUGEI and CEQEUGEI and to examine the test-retest reliability of the Greek translations of the two questionnaires.…”

Editorial: Gone to Pot: Examining the Association Between Cannabis Use and Medical/Psychiatric Disorders

“…Yet our understanding of this association remains incomplete. Multiple lines of evidence ranging from epidemiological studies (3)(4)(5) [both cross-sectional and within-subject studies (6)], human laboratory studies using delta-9 tetrahydrocannabinol, the main psychoactive constituent in cannabis (7,8), and more recently, genetic studies (9,10) suggest that cannabis use is a risk factor for the later development of psychosis. The association is moderated by additional factors such as onset of use in adolescence, exposure to childhood trauma and other environmental risk factors, and presence of additional symptoms such as perceived stress, anxiety and depression (11)(12)(13).…”