Carsten Hjorthøj1,2, Nikolai Albert1, Merete Nordentoft1,2; 1Copenhagen University Hospital, Mental Health Center Copenhagen, 2The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
Objective To investigate whether substance use disorders, in particular cannabis use disorder, predict conversion to schizophrenia in people with schizotypal disorder. Methods Prospective cohort study in the nationwide, unselected Danish registers. We identified all people born since 1981 in Denmark with incident diagnosis of schizotypal disorder, without previous diagnosis of schizophrenia (n=2,539). We estimated hazard ratios for conversion to schizophrenia for cannabis and other substance use disorders and antipsychotic medication, and adjusted for parental history of mental disorders, sex, birth year, and calendar year Results After two years, 16.3% (95% CI 14.8%-17.8%) of the people with schizotypal disorder had converted 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%) in those with cannabis use disorders. In fully adjusted models, any substance use disorder predicted conversion to schizophrenia (HR=1.34, 95% CI 1.11-1.63). Dividing by substances, 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) predicted conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotic medication, functional level before incident schizotypal disorder, or parental history of mental disorders. Conclusions and relevance Substance use disorders, in particular cannabis, amphetamines, and opioids, are important predictors of conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for both universal and substance-targeted prevention in people with schizotypal disorder.
