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This study examines the impact of acute infections on the risk of developing severe mental illness using health records.

May 29, 2026Open Access

Infections and severe mental illness: a population-based matched cohort study

Key Points

This study examines the impact of acute infections on the risk of developing severe mental illness using health records.
Conducted six matched cohort studies using data from the UK Clinical Practice Research Datalink Aurum.
Matched adults with specific infections to those without based on age, sex, and practice using electronic health records.
Estimated hazard ratios for severe mental illness using Cox regression adjusted for potential confounders.
Each infection increased the risk of severe mental illness: SSTI HR 1.16 (95% CI 1.08-1.24), LRTI HR 1.28 (95% CI 1.20-1.38), UTI HR 1.44 (95% CI 1.31-1.58), GE HR 1.53 (95% CI 1.42-1.65).
Sepsis associated with HR 1.69 (95% CI 1.52-1.88); meningitis/encephalitis showed highest risk at HR 3.36 (95% CI 2.61-4.32).
Findings indicate a significant association between various acute infections and an increased risk of severe mental illness.

Abstract

Background It is unclear whether acute infections associated with short-term systemic inflammation influence the risk of severe mental illness (SMI). Objective To investigate relationships between acute infections and incident SMI using electronic health records from the UK. Methods Using data from the Clinical Practice Research Datalink Aurum (1 January 2007 to 15 June 2024), we conducted six matched cohort studies. Adults (≥18 years) with gastroenteritis (GE), lower respiratory tract infection (LRTI), skin and soft tissue infection (SSTI), urinary tract infection (UTI), sepsis and meningitis/encephalitis (positive control exposure) recorded in primary care were matched with up to five individuals without infection on age, sex and practice in calendar date order and followed for incident SMI (schizophrenia, bipolar disorder, other psychoses). We estimated HRs for SMI comparing those with and without each infection using Cox regression, stratified by match set, adjusting for potential confounders (deprivation, Charlson Comorbidity Index, alcohol, smoking, body mass index and ethnicity). Findings Our six study cohorts ranged from 2 089 168 adults (391 773 with SSTI, 1 697 395 without) to 106 155 (17 860 with meningitis/encephalitis, 88 295 without). Median follow-up ranged from 4.1 years (IQR 1.9–6.9) in the sepsis cohort to 5.7 years (IQR 2.6–9.8) in the meningitis/encephalitis cohort. After adjustment, each infection was associated with increased SMI risk: SSTI, HR 1.16 (95% CI 1.08 to 1.24); LRTI, 1.28 (95% CI 1.20 to 1.38); UTI, 1.44 (95% CI 1.31 to 1.58); GE, 1.53 (95% CI 1.42 to 1.65); sepsis, 1.69 (95% CI 1.52 to 1.88); and meningitis/encephalitis, 3.36 (95% CI 2.61 to 4.32). Conclusion Our findings suggest SMI risk is higher among adults with a range of acute infections compared with those without, with higher risks for the more severe infections meningitis/encephalitis and sepsis. Clinical implications Providing timely infection treatment, targeted mental health support following severe infections, and where appropriate offering relevant vaccinations, may limit SMI risk.

Infections and severe mental illness: a population-based matched cohort study

Key Points

Abstract

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