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

It is unclear whether acute infections associated with short-term systemic inflammation influence the risk of severe mental illness (SMI).

To investigate relationships between acute infections and incident SMI using electronic health records from the UK.

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).

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).

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.

Providing timely infection treatment, targeted mental health support following severe infections, and where appropriate offering relevant vaccinations, may limit SMI risk.