From the Journals

Severe infection tied to substance-induced psychosis, conversion to schizophrenia


Severe infection is linked to an increased risk of substance-induced psychosis and subsequent conversion to schizophrenia, new research suggests.

Results of the large, population-based study showed any infection was associated with a 30% increased risk for substance-induced psychosis. However, with more than a threefold increased risk for substance-induced psychosis, hepatitis was the infection most strongly linked to psychosis and the only infection associated with conversion to schizophrenia.

“Severe infections are associated with an increased risk of developing a substance-induced psychosis. Furthermore, hepatitis following substance-induced psychosis is associated with an increase in the risk of conversion to schizophrenia. Both of these observations support the hypothesis of an immunological component to psychosis,” wrote the investigators, led by Carsten Hjorthøj, PhD, MSc, Copenhagen Research Center for Mental Health, Denmark.

The study was published online Feb. 12 in the American Journal of Psychiatry.

Mechanism still poorly understood

Previous research suggests that infection increases the risk for schizophrenia, but this new study is the first to investigate the association between infection and substance-induced psychosis.

Using Danish national registry data, the researchers analyzed data on all individuals born in Denmark since 1981. Of the 2,256,779 people, the researchers identified 3,618 cases of incident substance-induced psychosis.

Any infection increased the risk for substance-induced psychosis in the fully-adjusted model (hazard ratio = 1.30; 95% confidence interval, 1.22–1.39; P less than .001). The risk was doubled in the first 2 years following a severe infection and stayed elevated for more than 20 years.

Hepatitis was the infection most strongly associated with substance-induced psychosis (HR = 3.42; 95% CI, 2.47–4.74; P less than .001) and only hepatitis predicted conversion to schizophrenia after substance-induced psychosis (HR = 1.87; 95% CI, 1.07–3.26; P = .03).

These results, the investigators note, “mirror previous findings on the association between infections and schizophrenia, including previous observations that the link is particularly strong for hepatitis.”

They also point out that the biological mechanisms through which infections would increase the risk for psychosis, including substance-induced psychosis, remain poorly understood.

“If the exact mechanisms underlying the psychotogenic properties of infections or the immune response can be identified, this is likely to lead to improvements in treatment for psychotic disorders. A further hope is that it may even be possible to use this knowledge for primary prevention of psychosis,” the authors wrote.

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