Infections as a Risk Factor for and Prognostic Factor After Substance-Induced Psychoses

Am J Psychiatry. 2020 Apr 1;177(4):335-341. doi: 10.1176/appi.ajp.2019.19101047. Epub 2020 Feb 12.


Objective: Previous studies have suggested that infections increase the risk of schizophrenia. In this study, the authors aimed to investigate 1) whether infections increase the risk of substance-induced psychosis, and 2) whether infections increase the risk of converting from substance-induced psychosis to schizophrenia.

Methods: The study data were drawn from the combined nationwide Danish registers and included all people born in Denmark since 1981. The authors used Cox proportional hazards regression with infections as time-varying covariates, estimating hazard ratios and 95% confidence intervals. Infections were operationalized both as any infection and by the site of infection.

Results: The study included 2,256,779 individuals, for whom 3,618 cases of incident substance-induced psychosis were recorded. Any infection increased the risk of substance-induced psychosis (hazard ratio=1.30, 95% CI=1.22-1.39). For the first 2 years, the risk was doubled. Hepatitis was the infection most strongly associated with substance-induced psychosis (hazard ratio=3.42, 95% CI=2.47-4.74). Different types of infections were linked with different types of substance-induced psychosis. Most associations remained significant after controlling for potential confounders, such as substance use disorders. Only hepatitis predicted conversion to schizophrenia after substance-induced psychosis (hazard ratio=1.87, 95% CI=1.07- 3.26).

Conclusions: The study results support the hypothesis of an immunological component to psychosis.

Keywords: Infection; Risk; Schizophrenia; Substance-Induced Psychosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Central Nervous System Infections / epidemiology
  • Denmark / epidemiology
  • Disease Progression
  • Female
  • Gastroenteritis / epidemiology
  • Hepatitis / epidemiology
  • Humans
  • Incidence
  • Infections / epidemiology*
  • Male
  • Prognosis
  • Proportional Hazards Models
  • Psychoses, Substance-Induced / epidemiology*
  • Reproductive Tract Infections / epidemiology
  • Respiratory Tract Infections / epidemiology
  • Risk Factors
  • Schizophrenia / epidemiology*
  • Sepsis / epidemiology
  • Skin Diseases, Infectious / epidemiology
  • Urinary Tract Infections / epidemiology
  • Young Adult