Marijuana use in the immediate 5-year premorbid period is associated with increased risk of onset of schizophrenia and related psychotic disorders

Abstract

Objectives Several studies suggest that adolescent marijuana use predicts earlier age at onset of schizophrenia, which is a crucial prognostic indicator. Yet, many investigations have not adequately established a clear temporal relationship between the use and onset. Methods We enrolled 247 first-episode psychosis patients from six psychiatric units and collected data on lifetime marijuana/alcohol/tobacco use, and ages at onset of prodrome and psychosis in 210 of these patients. Cox regression (survival analysis) was employed to quantify hazard ratios (HRs) for effects of diverse premorbid use variables on psychosis onset. Results Escalation of premorbid use in the 5 years prior to onset was highly predictive of an increased risk for onset (e.g., increasing from no use to daily use, HR=3.6, p<0.0005). Through the analysis of time-specific measures, we determined that daily use approximately doubled the rate of onset (HR=2.2, p<0.0005), even after controlling for simultaneous alcohol/tobacco use. Building on previous studies, we were able to determine that cumulative marijuana exposure was associated with an increased rate of onset of psychosis (p=0.007), independent of gender and family history, and this is possibly the reason for age at initiation of marijuana use also being associated with rate of onset in this cohort. Conclusions These data provide evidence of a clear temporal relationship between escalations in use in the five years pre-onset and an increased rate of onset, demonstrate that the strength of the association is similar pre- and post-onset of prodromal symptoms, and determine that early adult use may be just as important as adolescent use in these associations.

Cannabis use and psychotic‐like experiences trajectories during early adolescence: the coevolution and potential mediators

“…Altogether, these findings are consistent with a recent study evaluating the different patterns of change in cannabis use on subsequent psychosis onset (Kelley et al, 2016). The authors reported that (a) the steeper the growth in cannabis use in the few years before conversion to psychosis, the higher the risk of conversion, and (b) those with an early onset of cannabis use who follow a decreasing trajectory of use have a similar risk of psychosis onset to nonusers (Kelley et al, 2016). Therefore, it seems that both age of onset and cumulative use information are insufficient measures and are likely to underestimate the real-life impact of cannabis use on psychotic symptoms.…”

“…Adolescents were shown to be at 159% increased odds of being classified in the increasing PLE trajectory for every unit increment in the cannabis frequency scale (which ranges from no use, occasional use, once a month, once a week, couple times per week, to every day). Altogether, these findings are consistent with a recent study evaluating the different patterns of change in cannabis use on subsequent psychosis onset (Kelley et al., ). The authors reported that (a) the steeper the growth in cannabis use in the few years before conversion to psychosis, the higher the risk of conversion, and (b) those with an early onset of cannabis use who follow a decreasing trajectory of use have a similar risk of psychosis onset to nonusers (Kelley et al., ).…”

Personality domains, duration of untreated psychosis, functioning, and symptom severity in first-episode psychosis

“…As part of a larger project examining the effects of premorbid marijuana use on early-course psychosis (Kelley et al, 2015), 104 patients (recruited and assessed between August 2008 and March 2011) had available data on the key variables of interest in this analysis. Participants were recruited from the inpatient psychiatric units ( n =82) or psychiatric emergency service ( n =5) of a large, urban, university-affiliated, public sector hospital and from a suburban county psychiatric crisis center ( n =17), both in Atlanta, Georgia, and both of which serve a predominantly African American population.…”

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.…”