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Causal associations between severe mental illness and sepsis: a Mendelian randomization study

Ruhao Yang1, Hongyu Xiang2, Ting Zheng3

  • 1Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, China.

Frontiers in Psychiatry
|March 27, 2024
PubMed
Abstract

Insights

Severe mental illness (SMI) may increase sepsis risk. Mendelian randomization found a suggestive link between major depression and higher sepsis risk, but not schizophrenia. No causal link was found for sepsis mortality.

Area of Science:

  • Genetics and Epidemiology
  • Infectious Disease Research

Background:

  • Observational studies suggest severe mental illness (SMI) is a risk factor for sepsis.
  • The causal relationship between SMI and sepsis remains unconfirmed.

Purpose of the Study:

  • To investigate the causal association between SMI and sepsis risk.
  • To examine the causal link between SMI and sepsis mortality using Mendelian randomization.

Main Methods:

  • Genome-wide association study (GWAS) data for major depression and schizophrenia (exposures) and sepsis/sepsis mortality (outcomes).
  • Selection of genetic variants (SNPs) associated with exposures as instrumental variables.
  • Inverse-variance weighted (IVW) method, with heterogeneity and pleiotropy tests (Cochrane's Q, MR-Egger).

Main Results:

  • Genetically predicted major depression showed a suggestive association with increased sepsis risk (OR=1.13, P=0.023).
  • No significant association was found between schizophrenia and sepsis risk (OR=1.00, P=0.811).
  • No causal evidence linked genetically predicted SMI to sepsis mortality; no heterogeneity or pleiotropy detected.

Conclusions:

  • Genetically predicted major depression is suggestively associated with elevated sepsis risk in European ancestry populations.
  • Clinicians should consider sepsis risk in patients with depression to potentially reduce incidence.
Keywords:
Mendelian randomizationcausal relationshipmajor depressionschizophreniasepsis

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