Research published in JAMA Psychiatry indicated an association between substance use disorders, particularly cannabis use, and conversion from schizotypal disorder to schizophrenia.

Researchers conducted a prospective cohort study with 2539 participants (57% men) with incident schizotypal disorder. Participants were of a mean age (standard deviation) of 20.9 (4.4) years. Data collection captured conversion to schizophrenia, substance use disorders, and antipsychotic medication use. Cox regression analyses adjusted for parental history of mental disorders, sex, birth year, and calendar year.

The conversion rates (95% CI) in the general cohort after 2 and 20 years of follow-up were 16.3% (14.8%-17.8%) and 33.1% (29.3%-37.3%), respectively. In those with cannabis use disorders, the 20-year conversion rate was 58.2% (44.8%-72.2%). According to fully adjusted models, any substance use disorder (hazard ratio [HR] 1.34; 95% CI, 1.11-1.63), cannabis use disorder (HR 1.30; 95% CI, 1.01-1.68), amphetamine use disorder (HR 1.90; 95% CI, 1.14-3.17), and opioid use disorder (HR 2.74; 95% CI, 1.38-5.45) were associated with an elevated risk for conversion to schizophrenia. Even after adjusting for concurrent use of antipsychotic medications, functional level before incident schizotypal disorder, and parental history of mental disorders, these associations remained significant. Other substance use disorders, including alcohol abuse, were associated with conversion to schizophrenia in the basically adjusted model (HR 1.59; 95% CI, 1.18-2.15), although not in the fully adjusted model. Based on sensitivity analyses, cannabis use disorder with onset prior to incident schizotypal disorder was not associated with conversion (HR 1.00; 95% CI, 0.70-1.41; P =.98).

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Researchers suggested that future studies should incorporate a larger patient cohort and adjust for additional factors, such as tobacco use. These data may be helpful in titrating care for those with schizotypal disorder and comorbid substance abuse disorders to mitigate the risk for conversion to schizophrenia. 


Hjorthøj C, Albert N, Nordentoft M. Association of substance use disorders with conversion from schizotypal disorder to schizophrenia [published online April 25, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.0568