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Substance abuse may raise schizophrenia risk in individuals with schizotypal disorder

Roshini Claire Anthony
16 May 2018

Individuals with incident schizotypal disorder and substance use disorders, particularly opioid, amphetamine, or cannabis use disorders, have an increased risk of developing schizophrenia, according to a recent study from Denmark.

“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,” said the researchers.

Using the Danish Psychiatric Central Research Register, researchers of this population-based, prospective cohort study identified 2,539 individuals with incident schizotypal disorder (mean age at first diagnosis 20.9 years, 43 percent female).

The overall rate of conversion from schizotypal disorder to schizophrenia at 1 and 2 years was 11.7 and 16.3 percent, respectively, which increased to 33.1 percent at 20 years. The conversion rate at 20 years was especially evident among individuals with cannabis use disorders (58.2 percent) and alcohol use disorders (47.0 percent), compared with those without any substance use disorder (30.6 percent).

Any substance use disorder was associated with an elevated risk of conversion from schizotypal disorder to schizophrenia (hazard ratio [HR], 1.34, 95 percent confidence interval [CI], 1.11–1.63). [JAMA Psychiatry 2018;doi:10.1001/jamapsychiatry.2018.0568]

In terms of specific substances, the risk of conversion to schizophrenia was increased among individuals with opioid use disorders (HR, 2.74, 95 percent CI, 1.38–5.45), amphetamine use disorders (HR, 1.90, 95 percent CI, 1.14–3.17), and cannabis use disorders (HR, 1.30, 95 percent CI, 1.01–1.68).

“Because these substances are rather different, schizophrenia might not be associated with the substances but with the underlying addiction or even a selection mechanism,” said the researchers. “However, this process would not explain why the same results were not observed for the remaining substances,” they said.

Individuals with schizotypal disorder who were being treated with antipsychotic medications also had an increased risk of conversion to schizophrenia (HR, 1.42, 95 percent CI, 1.18–1.70), a finding that researchers put down to confounding due to high likelihood of antipsychotic medication prescriptions in patients with severe schizotypal disorder.

Individuals whose substance use disorders began prior to incident schizotypal disorder were not more likely to undergo conversion to schizophrenia than those whose substance use disorders began after incident schizotypal disorder, with the exception of those with opioid use disorder (HR, 2.59, 95 percent CI, 0.99–6.77; p=0.05).

Alcohol use disorder, low level of functioning, and parental mental illness were not associated with conversion from schizotypal disorder to schizophrenia.

“[A]n increased focus on how to prevent conversion from schizotypal disorder to schizophrenia is required. Preventing or treating substance use disorders, especially cannabis and amphetamine use disorders, may have some efficacy in reducing the additional risk attributable to substance use disorders but probably not below the already high baseline conversion rate,” said the researchers.

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