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

Abstract Background Long-term inflammation caused by central nervous system infections increases severe mental illness (SMI) risk, but we do not know whether shorter-term inflammation due to other acute infections is associated with SMI risk. Our study aimed to investigate relationships between acute infections and SMI diagnosis using UK population-based electronic health records. Methods We conducted a series of matched cohort studies in adults aged 18+years, using Clinical Practice Research Datalink Aurum data, (01-03-2007-31-03-2023). Cohorts of individuals with each infection (sepsis, lower respiratory tract infection (LRTI) gastroenteritis; urinary tract infection (UTI), skin and soft tissue infection (SSTI); encephalitis/meningitis [positive control exposure]) were matched (age, sex, general practice, calendar period) with up to five adults without infection. We used Cox regression, accounted for matching and adjusted for confounders, to estimate hazard ratios (HRs) for incident SMI in those with and without infection. Results Our study cohorts ranged from the largest of 2,367,777 adults (393,968 with SSTI, 1,973,809 without) to the smallest of 109,314 (18,112 with meningitis/encephalitis, 91,202 without). Median age ranged from 43 years (IQR 30,60) in the meningitis/encephalitis cohort to 73 (IQR:60,83) in the sepsis cohort. Median follow-up time ranged from 4.1 years (IQR:1.8,6.8) in the UTI cohort to 6.3 (IQR:2.6,10.9) in the LRTI cohort. In adjusted models, each infection was associated with increased SMI hazards (SSTI, HR 1.15, 95%CI 1.10-1.21; LRTI, 1.18, 1.12-1.24; GE, 1.33, 1.27-1.40; UTI, 1.28, 1.20-1.37; sepsis, 1.65, 1.51-1.79; encephalitis/meningitis, 2.76, 2.29-3.34). Conclusions Our findings suggest SMI risk is higher among adults with acute infections, compared to those without, with higher risk in more severe infections. Providing timely infection treatment, mental health support, and where appropriate offering relevant vaccinations, may limit SMI. Key messages • Acute infections affecting different organ systems are associated with an increased risk of severe mental illness among adults. • Early treatment interventions combined with monitoring mental health during and after an infection, may improve mental health outcomes and limit progression to severe mental illness.