Substance use linked to conversion to schizophrenia

People with schizotypal disorder who use cannabis, amphetamines, and opioids might be more likely to convert to schizophrenia, according to a prospective cohort study.

The study, published online April 25 by JAMA Psychiatry, involved 2,539 Danish individuals with incident schizotypal disorder – but without a diagnosis of schizophrenia – who had been followed from birth.

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After 20 years of follow-up, about one-third (33.1%) of the total cohort had converted to schizophrenia. Among individuals without any substance use disorder, the conversion rate was 30.6%, while among individuals with cannabis use disorders, the conversion rate was 58.2%. Meanwhile, those with alcohol use disorder had a conversion rate of 47%, reported Carsten Hjorthøj, PhD, of Copenhagen University Hospital, Mental Health Center Copenhagen, and coauthors.

Participants with any substance use disorder had a 34% higher risk of converting to schizophrenia, but the risk was more than twofold higher with opioid use disorder (hazard ratio, 2.74; 95% confidence interval, 1.38-5.45), 30% higher with cannabis use disorder, and 90% higher with amphetamine use disorder.

Patients who had been prescribed antipsychotics also showed a higher risk of converting to schizophrenia (HR, 1.42; 95% CI, 1.18-1.70), which the authors suggested might reflect the fact that these patients were likely to be the most severely ill.

These associations were found even after adjustment for factors such as sex, birth year, all other individual types of substance use disorders, and parental mental disorders.

Dr. Hjorthøj and coauthors said the association between cannabis use and conversion to schizophrenia might be causal. “First, the association appears to be dose-dependent; second, the association is stronger for more potent types of cannabis; third, cannabis use is associated with earlier onset of psychosis; and fourth, age at onset of cannabis use is associated with age at onset of schizophrenia,” they wrote.

However, they also acknowledged that schizophrenia itself might increase the risk of individuals starting to use cannabis and other substances – a theory supported by the wide range of substances associated with conversion to schizophrenia.

“In our study, the first registered date of substance use disorder came before the first registered date of schizophrenia, but delays in diagnoses may have caused schizophrenia or its preclinical symptoms to predate substance use.”

The association between alcohol use disorder and conversion to schizophrenia was seen only in sensitivity analyses that ignored the birth year of the cohort, which the authors suggested may have been the result of increased power in this analysis.

Among the limitations cited by the authors was their inability to validate the schizotypal disorder diagnoses. Also, they wrote, the participants’ diagnoses were based on ICD-8 and ICD-10 criteria, and it was unclear whether the study results are generalizable to DSM-5 diagnoses.

The Lundbeck Foundation supported the study. No conflicts of interest were declared.

SOURCE: Hjorthøj C et al. JAMA Psychiatry. 2018 Apr 25. doi: 10.1001/jamapsychiatry.2018.0568.

People with schizotypal disorder who use cannabis, amphetamines, and opioids might be more likely to convert to schizophrenia, according to a prospective cohort study.

The study, published online April 25 by JAMA Psychiatry, involved 2,539 Danish individuals with incident schizotypal disorder – but without a diagnosis of schizophrenia – who had been followed from birth.

sdominick/iStock/Getty Images

After 20 years of follow-up, about one-third (33.1%) of the total cohort had converted to schizophrenia. Among individuals without any substance use disorder, the conversion rate was 30.6%, while among individuals with cannabis use disorders, the conversion rate was 58.2%. Meanwhile, those with alcohol use disorder had a conversion rate of 47%, reported Carsten Hjorthøj, PhD, of Copenhagen University Hospital, Mental Health Center Copenhagen, and coauthors.

Participants with any substance use disorder had a 34% higher risk of converting to schizophrenia, but the risk was more than twofold higher with opioid use disorder (hazard ratio, 2.74; 95% confidence interval, 1.38-5.45), 30% higher with cannabis use disorder, and 90% higher with amphetamine use disorder.

Patients who had been prescribed antipsychotics also showed a higher risk of converting to schizophrenia (HR, 1.42; 95% CI, 1.18-1.70), which the authors suggested might reflect the fact that these patients were likely to be the most severely ill.

These associations were found even after adjustment for factors such as sex, birth year, all other individual types of substance use disorders, and parental mental disorders.

Dr. Hjorthøj and coauthors said the association between cannabis use and conversion to schizophrenia might be causal. “First, the association appears to be dose-dependent; second, the association is stronger for more potent types of cannabis; third, cannabis use is associated with earlier onset of psychosis; and fourth, age at onset of cannabis use is associated with age at onset of schizophrenia,” they wrote.

However, they also acknowledged that schizophrenia itself might increase the risk of individuals starting to use cannabis and other substances – a theory supported by the wide range of substances associated with conversion to schizophrenia.

“In our study, the first registered date of substance use disorder came before the first registered date of schizophrenia, but delays in diagnoses may have caused schizophrenia or its preclinical symptoms to predate substance use.”

The association between alcohol use disorder and conversion to schizophrenia was seen only in sensitivity analyses that ignored the birth year of the cohort, which the authors suggested may have been the result of increased power in this analysis.

Among the limitations cited by the authors was their inability to validate the schizotypal disorder diagnoses. Also, they wrote, the participants’ diagnoses were based on ICD-8 and ICD-10 criteria, and it was unclear whether the study results are generalizable to DSM-5 diagnoses.

The Lundbeck Foundation supported the study. No conflicts of interest were declared.

SOURCE: Hjorthøj C et al. JAMA Psychiatry. 2018 Apr 25. doi: 10.1001/jamapsychiatry.2018.0568.

People with schizotypal disorder who use cannabis, amphetamines, and opioids might be more likely to convert to schizophrenia, according to a prospective cohort study.

The study, published online April 25 by JAMA Psychiatry, involved 2,539 Danish individuals with incident schizotypal disorder – but without a diagnosis of schizophrenia – who had been followed from birth.

sdominick/iStock/Getty Images

After 20 years of follow-up, about one-third (33.1%) of the total cohort had converted to schizophrenia. Among individuals without any substance use disorder, the conversion rate was 30.6%, while among individuals with cannabis use disorders, the conversion rate was 58.2%. Meanwhile, those with alcohol use disorder had a conversion rate of 47%, reported Carsten Hjorthøj, PhD, of Copenhagen University Hospital, Mental Health Center Copenhagen, and coauthors.

Participants with any substance use disorder had a 34% higher risk of converting to schizophrenia, but the risk was more than twofold higher with opioid use disorder (hazard ratio, 2.74; 95% confidence interval, 1.38-5.45), 30% higher with cannabis use disorder, and 90% higher with amphetamine use disorder.

Patients who had been prescribed antipsychotics also showed a higher risk of converting to schizophrenia (HR, 1.42; 95% CI, 1.18-1.70), which the authors suggested might reflect the fact that these patients were likely to be the most severely ill.

These associations were found even after adjustment for factors such as sex, birth year, all other individual types of substance use disorders, and parental mental disorders.

Dr. Hjorthøj and coauthors said the association between cannabis use and conversion to schizophrenia might be causal. “First, the association appears to be dose-dependent; second, the association is stronger for more potent types of cannabis; third, cannabis use is associated with earlier onset of psychosis; and fourth, age at onset of cannabis use is associated with age at onset of schizophrenia,” they wrote.

However, they also acknowledged that schizophrenia itself might increase the risk of individuals starting to use cannabis and other substances – a theory supported by the wide range of substances associated with conversion to schizophrenia.

“In our study, the first registered date of substance use disorder came before the first registered date of schizophrenia, but delays in diagnoses may have caused schizophrenia or its preclinical symptoms to predate substance use.”

The association between alcohol use disorder and conversion to schizophrenia was seen only in sensitivity analyses that ignored the birth year of the cohort, which the authors suggested may have been the result of increased power in this analysis.

Among the limitations cited by the authors was their inability to validate the schizotypal disorder diagnoses. Also, they wrote, the participants’ diagnoses were based on ICD-8 and ICD-10 criteria, and it was unclear whether the study results are generalizable to DSM-5 diagnoses.

The Lundbeck Foundation supported the study. No conflicts of interest were declared.

SOURCE: Hjorthøj C et al. JAMA Psychiatry. 2018 Apr 25. doi: 10.1001/jamapsychiatry.2018.0568.