Infections—a Risk Factor for Developing Substance-Induced Psychosis

This electron micrograph shows numerous hepatitis virions, strain unknown, which are etiologic agents for viral hepatitis. In the United States, viral hepatitis is an important public health problem because it causes serious illness, it affects millions, and it has a close connection with HIV. There are five identified types of viral hepatitis and each one is caused by a different virus. In the United States, hepatitis A, hepatitis B and hepatitis C are the most common types. Date: XXXX Content credits: / xxxxx Photo credit: Xxxxxxxxxx Image storage: VEC/ GHO storage Support File: CD_124_DH/ 003 URL: URL Title: CDC – National Center for Infectious Diseases – Viral Hepatitis
Infections raised the risk for substance-induced psychosis, with the risk doubled for the first 2 years. The largest increase in risk was observed for hepatitis.

Severe infections are associated with an increase in the risk of developing substance-induced psychosis, according to a recent study published in the American Journal of Psychiatry. No studies have previously investigated whether substance-induced psychosis has an immune-related component, and little is known about factors that predispose individuals to developing schizophrenia after substance-induced psychosis.

Researchers examined data from nationwide Danish registers, including longitudinal information on diagnosed infections and substance-induced psychosis. The study included 2,256,779 individuals and 3618 recorded cases of substance-induced psychosis. The researchers studied the role of infections in the development of substance-induced psychosis, as well as conversion from substance-induced psychosis, using Cox proportional hazards regression.

Infections raised the risk for substance-induced psychosis (hazard ratio [HR], 1.30; 95% CI, 1.22-1.39), with the risk doubled for the first 2 years. The largest increase in risk was observed for hepatitis (HR, 3.42; 95% CI, 2.47-4.74), with cocaine and amphetamine being the main drivers of psychosis. Typically, infections elevated the risk for all types of substance-induced psychosis except hallucinogen-induced psychosis. There was a 50% or more increased risk for substance-induced psychosis with sepsis (HR, 1.66; 95% CI, 1.32-2.09), skin infections (HR, 1.69; 95% CI, 1.52-1.87), and urogenital infections (HR, 2.30; 95% CI, 1.91-2.76).

Only hepatitis predicted conversion to schizophrenia after substance-induced psychosis in all adjusted models (HR, 1.87; 95% CI, 1.07-3.26).

Limitations included the reliance on treatment registers of the secondary health care sector for infections, substance-induced psychosis, and conversions to schizophrenia. In addition, only the most severe infections were identified, as many infections do not require hospitalization, and the results may not be generalized to people getting severe infections in their 40s and beyond. However, the study authors concluded that the study findings strongly support the hypothesis of “an immunological component to psychosis,” which can potentially be used for primary preventative efforts.

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“Since hepatitis is also linked to injection drug use, there may also be an argument for reducing the infection rate in substance users by supplying injection drug users with clean syringes,” the investigators concluded, “The positive health impacts of such an intervention would naturally go far beyond those related to substance induced psychosis.”


Hjorthok C, Kejsr Starzer MS, Benros ME, Nordentoft M. Infections as a risk factor for and prognostic factor after substance-induced psychoses [published online February 12, 2020]. Am J Psychiatry. doi:10.1176/appi.ajp.2019.19101047