Immune-Related Comorbidities in Childhood-Onset Obsessive Compulsive Disorder: Lifetime Prevalence in the Obsessive Compulsive Disorder Collaborative Genetics Association Study

Abstract

Objective: To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives.Methods: Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Genetics Association Study. Lifetime prevalence of immune-related diseases was compared with the highest available population estimate and reported as a point estimate with 95% adjusted Wald interval. Worst-episode OCD severity and symptom dimensions were assessed with the Yale–Brown Obsessive Compulsive Scale (YBOCS) and Symptom Checklist (YBOCS-CL).Results: Probands reported higher-than-expected prevalence of scarlet fever (4.0 [3.1–5.2]% vs. 1.0%–2.0%, z = 1.491, p < 0.001, n = 1389), encephalitis or meningitis (1.4 [0.9–2.1]% vs. 0.1%–0.4%, z = 5.913, p < 0.001, n = 1393), rheumatoid arthritis (1.1 [0.6–2.0]% vs. 0.2%–0.4%, z = 3.416, p < 0.001, n = 949) and rheumatic fever (0.6 [0.3–1.2]% vs. 0.1%–0.2%, z = 3.338, p < 0.001, n = 1390), but not systemic lupus erythematosus, diabetes, asthma, multiple sclerosis, psoriasis, or inflammatory bowel disease. First-degree relatives reported similarly elevated rates of scarlet fever, rheumatic fever, and encephalitis or meningitis independent of OCD status. There was no association between worst-episode severity and immune-related comorbidities, although probands reporting frequent ear or throat infections had increased severity of cleaning-/contamination-related symptoms (mean factor score 2.5 ± 0.9 vs. 2.3 ± 1.0, t = 3.183, p = 0.002, n = 822).Conclusion: These data suggest high rates of streptococcal-related and other immune-mediated diseases in patients with childhood-onset OCD and are consistent with epidemiological studies in adults noting familial clustering. Limitations include potential reporting bias and absence of a control group, underscoring the need for further prospective studies characterizing medical and psychiatric disease clusters and their interactions in children. Such studies may ultimately improve our understanding of OCD pathogenesis and aid in the development of adjunctive immune-modulating therapeutic strategies.

Familial Clustering of Immune-Mediated Diseases in Children with Abrupt-Onset Obsessive Compulsive Disorder

“…Epidemiologic studies from Sweden and North America have consistently shown familial clustering of immune-mediated diseases in patients with OCD and tic disorders (Murphy et al 2010;Mataix-Cols et al 2018;Westwell-Roper et al 2019). Our findings of an increased risk of having immune-mediated disorders in firstdegree relatives of our patients with early abrupt-onset OCD are in line with those of Westwell-Roper et al (2019) in the general OCD population. When seeing patients with both abrupt-onset OCD and idiopathic OCD, clinicians should carefully evaluate families for immune disorders.…”

“…To the Editor: W e read with interest your June 2019 publication regarding the multi-site questionnaire study by Westwell-Roper et al (2019). The authors reported increased rates of immunemediated comorbidities among first-degree relatives of patients with obsessive compulsive disorder (OCD).…”

What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders?

“…There is also limited knowledge on whether the characteristics of tics and OCS may differ depending on prior/current exposure to infections. A recent report showed that young OCD patients with higher frequency of self-reported ear or throat infections have increased severity of cleaning/contamination-related symptoms ( 72 ), although an altered perception of their medical history and subsequent over-reporting might also explain this finding.…”

“…A potential limitation of this work is the likely under-representation of OCD patients who do not seek medical help. In relation to this, Westwell-Roper et al ( 72 ) published the largest to date clinic-based survey that estimated the lifetime prevalence of immune-related diseases using self-report medical questionnaires from 1,401 youth with OCD and 1,045 of their first-degree relatives enrolled in the OCD Collaborative Genetics Association Study. This descriptive study was limited by the lack of a control population, reliance on retrospective self-report and post-hoc evaluation of questionnaires that did not screen for all autoimmune comorbidities.…”

Obsessive-Compulsive Disorder With Rheumatological and Inflammatory Diseases: A Systematic Review

“…In the pediatric population, OCD has been linked to some antibodies for streptococcal infections, which can cross-react with other epitopes found on the neurons of the basal ganglia. Most commonly, this cross-reaction results in pediatric acute-onset neuropsychiatric syndrome (PANS) as well as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) [ 7 , 8 ].…”