title: Marijuana use in the immediate 5-year premorbid period is associated with increased risk of onset of schizophrenia and related psychotic disorders.
abstract: OBJECTIVE
  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 5years 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.
authors.affiliation: Rollins School of Public Health of Emory University, Department of Biostatistics and Bioinformatics, Atlanta, GA, United States.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Kelley
authors.affiliation: Tufts University School of Medicine, Physician Assistant Program, Boston, MA, United States.
authors.forename: Claire Ramsay
authors.initials: CR
authors.lastname: Wan
authors.affiliation: Lenox Hill Hospital, Department of Psychiatry, New York, NY, United States.
authors.forename: Beth
authors.initials: B
authors.lastname: Broussard
authors.affiliation: The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Crisafio
authors.affiliation: Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cristofaro
authors.affiliation: Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Johnson
authors.affiliation: The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Reed
authors.affiliation: Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Amar
authors.affiliation: Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, United States.
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: Kaslow
authors.affiliation: Emory University College of Arts and Sciences, Department of Psychology, Atlanta, GA, United States.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Walker
authors.affiliation: Lenox Hill Hospital, Department of Psychiatry, New York, NY, United States; Hofstra Northwell School of Medicine, Hempstead, NY, United States. Electronic address: mcompton@northwell.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Compton
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D002189:Marijuana Abuse / Q000453:epidemiology*; D062706:Prodromal Symptoms; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000453:epidemiology*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000453:epidemiology*; D016019:Survival Analysis; D055815:Young Adult
keywords: Age at onset; Cannabis; First-episode psychosis; Marijuana; Schizophrenia