Childhood-onset Obsessive-compulsive disorder (OCD) and tic disorders appear to arise, in some cases, as sequelae of common childhood infections, including Group A beta-hemolytic streptococcal (GABHS) infections. Children whose symptoms onset or exacerbate following GABHS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The subgroup shares several common clinical characteristics in common, and also may share a common pathophysiology for their symptoms. Investigations of the nature and treatment of this novel subgroup are ongoing. In addition, studies of Sydenhams chorea (the neurological manifestation of rheumatic fever) are continuing to determine the nature of the post-streptococcal autoimmunity, as well as to identify more effective treatment strategies. During this reporting period, a paper was published in Lancet describing the efficacy of two immunomodulatory treatments - therapeutic plasma exchange and intravenous immunoglobulin (IVIG) for children with acute, severe OCD and tics. Both IVIG and plasma exchange were strikingly and significantly superior to placebo, with the average improvement exceeding 50% on some measures at one-month follow-up. Improvements were sustained at one year follow-up evaluations, as well. The mechanism of action of therapeutic plasma exchange is currently under investigation in the PANDAS cohort. We also published the results of an eight month long double-blind crossover trial of penicillin prophylaxis (vs. placebo) for prevention of symptom exacerbations in children with PANDAS. Fourteen children had GABHS infections during the penicillin phase, which contributed to a failure to demonstrate superiority of the active treatment. Not only did this confirm that neuropsychiatric symptom exacerbations can be triggered by GABHS infections, but it also raises the larger question of the utility of oral penicillin prophylaxis (for rheumatic fever.) A study is currently underway to determine whether a more effective oral agent might be successful in preventing post-streptococcal symptom exacerbations. Other investigations include a longitudinal, school-based assessment of tic and GABHS frequencies, and a placebo-controlled trial of amoxicillin therapy. - Obsessive Compulsive Disorder, Tic disorders, Tourette syndrome, Anxiety Disorders, Pediatric psychopathology, PANDAS - Human Subjects

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002666-07
Application #
6290561
Study Section
Special Emphasis Panel (PDN)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1999
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
Snider, Lisa A; Lougee, Lorraine; Slattery, Marcia et al. (2005) Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry 57:788-92
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

Showing the most recent 10 out of 34 publications