Community-based infections and its association with mental disorder onset: a nationwide matched cohort study

Most studies assessing the association between infection accumulation and mental disorders focus on hospitalization-based severe infections. However, most infections are more common, and community acquired. This study aimed to evaluate the effects of community-based infection accumulation on risk to develop a mental disorder, and risk factors modulating this association. A nationwide population-based matched cohort study was conducted, utilizing the registries of Clalit Health Services, the largest healthcare organization in Israel. Individuals born between the years 1995–2005 with history of specific infections (n = 35 020) were propensity score matched to an unexposed group with no such history (n = 35 020). These individuals were followed up until 2024 for a mental disorder onset. Serology, nasal and saliva-based tests for cytomegalovirus, herpesviruses, hepatitis, influenza, or toxoplasma gondii starting from birth were identified, and patients were followed for onset of anxiety, depression schizophrenia and bipolar disorders. Individuals with history of infection accumulation demonstrated higher risk to develop a mental disorder, with risk gradually increasing after one (HR, 1.08, 95%CI, 1.01–1.17, p = 0.036), two (HR, 1.19, 95%CI, 1.09–1.30, p < 0.001) and three or more infections (HR, 1.81, 95%CI, 1.32–2.48, p < 0.001) up to first five years post-infection. These associations were stronger in females, individuals of older age and individuals with larger families. The findings suggest that community-based immune challenges might shape vulnerability for mental disorders, and stress the need to consider infection history in future efforts to develop patient-tailored prevention and intervention strategies.