Characterization of Childhood-Onset Obsessive-Compulsive Disorder
Condition: Obsessive-Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Observational

Summary: 
      The purpose of this study is to learn more about Obsessive-compulsive Disorder (OCD) in
      children. OCD usually has a slow onset, and symptoms that may remain at a stable level over
      time. A subset of children with OCD has a sudden onset and symptoms that fluctuate in
      severity over time. This study will also compare healthy children to those with OCD. This is
      an observational study; children who participate will not receive any new or experimental
      therapies.

      OCD affects nearly 1% of the pediatric population. The symptoms of this illness can interrupt
      development, causing significant psychological distress and producing life-long impairments
      in social, academic, and occupational functioning. A subgroup of pediatric OCD has been
      designated by the acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated
      with Streptococcal Infections). This type of OCD is characterized by sudden symptom onset and
      a relapsing-remitting course of illness; exacerbation of symptoms occurs with scarlet fever
      or strep. throat infections. This study will identify factors that distinguish children with
      PANDAS OCD from children with non-PANDAS OCD, and will compare both groups to healthy
      children.

      Children with OCD and their parents are screened with interviews and a review of the child's
      medical records. Participants have an initial evaluation that includes a psychiatric,
      physical and neuromotor exam, neuropsychological testing, psychological interviews, and a
      blood test. Structural magnetic resonance imaging (MRS) scans of the brain are also obtained.
      The MRS scan does not use radiation.

      After the initial evaluation, children with OCD have follow-up visits every 6 weeks for 12 to
      24 months. They are seen yearly for 8 years after the study. If they have a significant
      improvement or worsening of their symptoms, they are asked to make a maximum of two extra
      visits. Parents of OCD patients are called four times a year to discuss any changes in the
      child's condition between yearly visits. All participants have a 1-year follow-up visit upon
      study completion.
    

Detailed description: 
      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.
    

Keywords: Tic Disorders; Neurophyschological; Immunology; Magnetic Resonance Imaging; Basal Ganglia; Obsessive-Compulsive Disorder; Children; Adolescents; Magnetic Resonance Spectroscopy; PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated d; Obsessive Compulsive Disorder; OCD; Healthy Volunteers; HV