Association of Pre-Onset Cannabis, Alcohol, and Tobacco Use With Age at Onset of Prodrome and Age at Onset of Psychosis in First-Episode Patients

Abstract

Objective Several reports suggest that cannabis use is associated with an earlier age at onset of psychosis, though not all studies have operationalized cannabis use as occurring prior to onset of symptoms. This study addressed whether pre-onset cannabis use (and alcohol and tobacco use) is associated with an earlier age at onset of prodromal and psychotic symptoms. Additionally, effects of the progression of frequency of use were examined through time-dependent covariates in survival analyses. Method First-episode patients (n=109) hospitalized in two public-sector inpatient psychiatric units underwent in-depth cross-sectional/retrospective assessments. Prior substance use and ages at onset of prodromal and psychotic symptoms were determined using standardized methods. Cox regression modeling was conducted. Results Whereas classifying participants according to maximum frequency of use prior to onset (none, ever, weekly, or daily) revealed no significant effects of cannabis or tobacco use on risk of onset, analysis of change in frequency of use prior to onset indicated that progression to daily cannabis and tobacco use was associated with increased risk of onset of psychotic symptoms. Similar or even stronger effects were observed when onset of illness/prodromal symptoms was the outcome. A gender by daily cannabis use interaction was observed—progression to daily use resulted in a much larger increased relative risk of onset of psychosis in females than males. Conclusions Pre-onset cannabis use may hasten the onset of psychotic as well as prodromal symptoms. Age at onset is a key prognostic factor in schizophrenia, and discovering modifiable predictors of age at onset is crucial.

Does substance use disorder affect clinical expression in first-hospitalization patients with schizophrenia? Analysis of a prospective cohort

“…SUD patients look younger at onset of psychiatric symptoms (Modestin et al, 2001), more frequently male and smokers (Cantor-Graae et al, 2001), unmarried (Farrelly et al, 2007;Wobrock et al, 2007;Mazzoncini et al, 2010) and unemployed (Compton et al, 2009;Barrigón et al, 2010;Schimmelmann et al, 2011).…”

“…The substance most commonly used is cannabis, followed by cocaine, amphetamine, hallucinogen and other drugs (Allebeck et al, 1993;Hambrecht and Häfner, 2000;Compton et al, 2009Compton et al, , 2011. Moreover high frequency of polysubstance abuse and misuse are reported Barnett et al, 2007).…”

Suicide in schizophrenia

“…Drug abuse, particularly of cannabis, is frequent among patients with first-episode schizophrenia, and the age of onset of schizophrenia appears to be lower among cannabis abusers compared with both cannabis non-abusers and alcohol abusers [63,64]. Cannabis use appears to be associated with an increased risk for schizophrenia [65].…”

Investigation of the COMT Val158Met variant association with age of onset of psychosis, adjusting for cannabis use

“…This is consistent with earlier examinations of the cannabis–psychosis relationship (Andreasson, Allebeck, Engstrom, & Rydberg, 1987; Arseneault, Cannon, Witton, & Murray, 2004; Arseneault et al., 2002; Compton et al., 2009; Di Forti et al., 2009, 2014; Kelley et al., 2016; McLaren, Silins, Hutchinson, Mattick, & Hall, 2010; Moore et al., 2007) (for a meta‐analysis, see Large, Sharma, Compton, Slade, & Nielssen, 2011). The effect of gender on AoP was significant in our study, with males being at risk of developing psychosis earlier than females.…”

“…In a recent publication, however, rs4680 was not associated with AoP, neither independently nor in interaction with another genetic variant that has been previously studied in relation to psychosis and cannabis consumption, namely the BDNF Val66Met (Mané et al., 2017). The exact mechanism behind the association between rs4680 and AoP is not clear but cannabis is an important factor affecting AoP (Barnes, Mutsatsa, Hutton, Watt, & Joyce, 2006; Compton et al., 2009; Gonzalez‐Pinto et al., 2008). Other significant factors affecting AoP are gender (Mané et al., 2017) and family history of psychosis/schizophrenia (Byrne, Agerbo, & Mortensen, 2002; Kendler & MacLean, 1990).…”