Characterization of Childhood-Onset Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) affects nearly 1% of the pediatric population. The intrusive symptoms of this illness can interrupt normative development, causing significant psychological distress and producing life-long impairments in social, academic, and occupational functioning. Current research supports a neurobiologic model for OCD. Converging lines of evidence suggest that a post-infectious autoimmune-mediated process may be associated with the pathogenesis of some pediatric cases. This subgroup has been designated by the acronym, PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The abrupt symptom onset and relapsing-remitting course of illness characteristic of the PANDAS subgroup appears to define a distinct cohort of patients, in whom symptom exacerbations occur synchronously with Group A beta-hemolytic streptococcal (GABHS) infections.

We propose to perform prospective, longitudinal evaluations of a group of 72 children with recent onset OCD and 72 age-/sex-matched healthy volunteers. All children will undergo a comprehensive baseline assessment, including physical, neurological and psychiatric evaluations, neuropsychological testing, structural MRI and MRS scans, and laboratory assays. The children with OCD will be evaluated in the NIMH outpatient clinic at six-week intervals for a 28-month period to obtain prospective ratings of neuropsychiatric symptom severity, physical and neurological assessments, and anti-streptococcal antibody titers. At the end of the observation period, each OCD patient will be placed into a cohort based on the course of his or her symptoms: those displaying an acute onset and episodic course of OCD will be assigned to the "episodic" group, while those children with a gradual onset and stable course will comprise the "persistent" group. We hypothesize that the episodic group will have GABHS infections concurrent with their neuropsychiatric symptoms exacerbations and will meet criteria for the PANDAS subgroup. In contrast, children in the persistent group are not expected to have distinct periods of relapse nor a temporal association between GABHS infections and worsening of their symptoms. We expect that children in the PANDAS subgroup will demonstrate cross-reactive antibodies (antistreptococcal/antineuronal) during symptom exacerbations. At the conclusion of the study, we will perform group comparisons between the episodic OCD and persistent OCD cohorts, as well as between the patients and controls. The purpose of these comparisons is to identify baseline markers of membership in the PANDAS subgroup. The possibilities include distinctive HLA subtypes, quantitative differences in cytokines distribution, unique MRS chemical profiles, or a specific pattern of deficits on neuropsychological tests of basal ganglia function.