Prenatal and Early Childhood Infections and Subsequent Risk of Obsessive-Compulsive Disorder and Tic Disorders: A Nationwide, Sibling-Controlled Study

Postinfectious autoimmune processes are hypothesized to be causally related to both obsessive-compulsive disorder (OCD) and tic disorders, but current evidence is conflicting. This study examined whether prenatal maternal (and paternal, as an internal control) infections and early childhood infections in the offspring (i.e., during the first 3 years of life) were associated with a subsequent risk of OCD and Tourette syndrome or chronic tic disorder (TS/CTD).Individuals exposed to any prenatal maternal infection (n = 16,743) and early childhood infection (n = 264,346) were identified from a population-based birth cohort consisting of 2,949,080 singletons born in Sweden between 1973 and 2003 and were followed through 2013. Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Sibling analyses were performed to control for familial confounding.At the population level, and after adjusting for parental psychiatric history and autoimmune diseases, a significantly increased risk of OCD and TS/CTD was found in individuals exposed to prenatal maternal (but not paternal) infections (OCD: HR, 1.33; 95% CI, 1.12-1.57; TS/CTD: HR, 1.60; 95% CI, 1.23-2.09) and early childhood infections (OCD: HR, 1.19; 95% CI, 1.14-1.25; TS/CTD: HR, 1.34; 95% CI, 1.24-1.44). However, these associations were no longer significant in the sibling analyses.The results do not support the hypothesis that prenatal maternal or early-life infections play a direct causal role in the etiology of either OCD or TS/CTD. Instead, familial factors (e.g., genetic pleiotropy) may explain both the propensity to infections and the liability to OCD and TS/CTD.