Certain childhood neuropsychiatric disorders, including Sydenham's chorea Obsessive Compulsive Disorder (OCD) and Tourette's disorder, appear to be mediated (for a subgroup of these patients) through antibodies produced against Group A beta-hemolytic streptococcal infections which cross-react with neurons within the basal ganglia and other regions. This has led to the identification of a clear subtype of patients with OCD and Tourette's Disorder, who appear to distinguishable from other forms of OCD and movement disorders. This subtype is identified by acronym: PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptoccal infections). Volumetric MRI Examinations confirm basal ganglia involvement in Sydenham's chorea, while the preliminary success of immunomodulatory treatments, such as plasma exchange and intravenous immunoglobulin, suggest that the antibodies play an etiologic role. Ongoing treatment studies for this include immunomodulatory interventions (i.e. plasmapheresis, intravenous immunoglobulins) for Sydenham's Chorea and """"""""antineuronal mediated"""""""" OCD and tic disorders. Additionally, a double-blind controlled trial of penicillin versus placebo is underway in a group of children with OCD ( or tic disorders) to determine if they have fewer and less severe exacerbations during the penicillin treatment. Examinations of CSF obtained at follow-up of children wit OCD who had participated in the clomipramine/desipramine crossover investigation have shown """"""""normalization"""""""" of monoamines and neuroendocrine measures during clomopramine maintenance therapy. Of particular interest, somatostatin concentrations decreased and the growth rate of the affected children appeared to have increased. Longitudinal data are currently being examined from a subgroup of these children. Further, post-treatment PET scans were obtained from a cohort of patients with OCD to determine changes in patterns of cerebral blood flow following treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002666-03
Application #
5203810
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kalra, Simran K; Swedo, Susan E (2009) Children with obsessive-compulsive disorder: are they just ""little adults""? J Clin Invest 119:737-46
Murphy, Tanya K; Snider, Lisa A; Mutch, P Jane et al. (2007) Relationship of movements and behaviors to Group A Streptococcus infections in elementary school children. Biol Psychiatry 61:279-84
Grant, Paul; Lougee, Lorraine; Hirschtritt, Matthew et al. (2007) An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder. J Child Adolesc Psychopharmacol 17:761-7
Kirvan, Christine A; Cox, Carol J; Swedo, Susan E et al. (2007) Tubulin is a neuronal target of autoantibodies in Sydenham's chorea. J Immunol 178:7412-21
Stein, Dan J; Arya, Monisha; Pietrini, Pietro et al. (2006) Neurocircuitry of disgust and anxiety in obsessive-compulsive disorder: a positron emission tomography study. Metab Brain Dis 21:267-77
Kirvan, Christine A; Swedo, Susan E; Kurahara, David et al. (2006) Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea. Autoimmunity 39:21-9
Kirvan, Christine A; Swedo, Susan E; Snider, Lisa A et al. (2006) Antibody-mediated neuronal cell signaling in behavior and movement disorders. J Neuroimmunol 179:173-9
Swedo, Susan E; Grant, Paul J (2005) Annotation: PANDAS: a model for human autoimmune disease. J Child Psychol Psychiatry 46:227-34
Asbahr, Fernando R; Garvey, Marjorie A; Snider, Lisa A et al. (2005) Obsessive-compulsive symptoms among patients with Sydenham chorea. Biol Psychiatry 57:1073-6
Garvey, Marjorie A; Snider, Lisa A; Leitman, Susan F et al. (2005) Treatment of Sydenham's chorea with intravenous immunoglobulin, plasma exchange, or prednisone. J Child Neurol 20:424-9

Showing the most recent 10 out of 34 publications