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Original Investigation
July 2018

Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia

Author Affiliations
  • 1Copenhagen University Hospital, Mental Health Center Copenhagen, Hellerup, Denmark
  • 2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen and Aarhus, Denmark
JAMA Psychiatry. 2018;75(7):733-739. doi:10.1001/jamapsychiatry.2018.0568
Key Points

Question  Are substance use disorders, in particular cannabis use disorders, associated with conversion from schizotypal disorder to schizophrenia?

Findings  In this Danish nationwide, register-based cohort study that identified 2539 participants with incident schizotypal disorder, any substance use disorder was associated with conversion to schizophrenia at a rate of 33.1%; for cannabis use disorders, the conversion rate was 58.2%. Results were statistically significant after controlling for confounders.

Meaning  Universal and substance-targeted prevention efforts are needed to reduce conversion to schizophrenia in individuals with schizotypal disorder.

Abstract

Importance  Understanding the role of substance use disorders in conversion from schizotypal disorder to schizophrenia may provide physicians and psychiatrists with important tools for prevention or early detection of schizophrenia.

Objective  To investigate whether substance use disorders, in particular cannabis use disorder, are associated with conversion to schizophrenia in individuals with schizotypal disorder.

Design, Setting, and Participants  This prospective cohort study included a population-based sample of all individuals born in Denmark from January 1, 1981, through August 10, 2014, with an incident diagnosis of schizotypal disorder and without a previous diagnosis of schizophrenia. Follow-up was completed on August 10, 2014, and data were analyzed from March 10, 2017, through February 15, 2018.

Exposures  Information on substance use disorders combined from 5 different registers.

Main Outcomes and Measures  Cox proportional hazards regression using time-varying information on substance use disorders and receipt of antipsychotics and adjusted for parental history of mental disorders, sex, birth year, and calendar year were used to estimate hazard ratios (HRs) and 95% CIs for conversion to schizophrenia.

Results  A total of 2539 participants with incident schizotypal disorder were identified (1448 men [57.0%] and 1091 women [43.0%]; mean [SD] age, 20.9 [4.4] years). After 2 years, 16.3% (95% CI, 14.8%-17.8%) experienced conversion to schizophrenia. After 20 years, the conversion rate was 33.1% (95% CI, 29.3%-37.3%) overall and 58.2% (95% CI, 44.8%-72.2%) among those with cannabis use disorders. In fully adjusted models, any substance use disorder was associated with conversion to schizophrenia (HR, 1.34; 95% CI, 1.11-1.63). When data were stratified by substance, cannabis use disorders (HR, 1.30; 95% CI, 1.01-1.68), amphetamine use disorders (HR, 1.90; 95% CI, 1.14-3.17), and opioid use disorders (HR, 2.74; 95% CI, 1.38-5.45) were associated with conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders.

Conclusions and Relevance  Substance use disorders, in particular cannabis, amphetamines, and opioids, may be associated with conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.

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