Antinuclear, Cytoskeletal, Antineuronal Antibodies in the Serum Samples of Children with Tic Disorders and Obsessive Compulsive Disorders

Abstract

Objective: As environmental factors, the role of Group A beta hemolytic streptococcus infections in the development of tic and obsessive compulsive disorders (OCD) is controversial. The autoimmune hypothesis states that during infection, formation of autoantibodies leads to an autoimmune disorder, which in turn results in movement disorders, tic disorders and/or OCD. In order to test this hypothesis, we assayed these antibodies in children and adolescents diagnosed with tic disorders and/or OCD. Material and Methods: Children and adolescents who were diagnosed with either tic disorders or OCD according to DSM-IV criteria (n=28), were compared with healthy controls (n=15) having similar age and gender characteristics. Regardless of a streptococcus infection history, serum samples of all patients and controls underwent antinuclear, cytoskeletal, and antineuronal antibody assay using indirect immunofluorescence. Results: The rates of antinuclear antibody positivity were 21% and 20% in the patient and control groups respectively (p>0.05). Antineuronal antibody was positive in 2 (7%) of 28 patients versus in 1 (6%) of 15 controls (p>0.05). Conclusion: These results suggest that such antibodies may not be involved in the pathogenesis of tic disorders/OCD.

Keywords

• Tic disorders, obsessive compulsive disorder, PANDAS, autoimmunity, child

Antinuclear, Cytoskeletal, Antineuronal Antibodies in the Serum Samples of Children with Tic Disorders and Obsessive Compulsive Disorders

Öz

References

1. George MS, Trimble MR, Ring HA, Sallee FR, Robertson MM. Obsessions in OCD with and without Gilles de la Tourette’s Syn- drome. Am J Psychiatry 1993;150:93-7.
2. Leckman JF, Peterson BS, Cohen DJ. Tic Disorders. In: Lewis M (ed). Child and Adolescent Psychiatry. Philadelphia: Lippincott Williams&Wilkins; 2002: 734-44.
3. Leonard HL, Lenane MC, Swedo SE, Rettew DC, Gershon ES, Rapoport JL. Tics and Tourette’s Disorder: A 2 to 7-year fol- low up of 54 obsessive-compulsive children. Am J Psychiatry 1992;149:1244-51.
4. Towbin KE, Riddle MA. Obsessive-Compulsive Disorder. In: Lewis M(ed). Child and Adolescent Psychiatry. Philadelphia: Lippincott Williams & Wilkins; 2002: 834-47.
5. Allen AJ, Leonard HL, Swedo SE. Case study: a new infection- triggered, autoimmune subtype of pediatric OCD and Tourette’s Syndrome. J Am Acad Child Adolesc Psychiatry 1995;34:307-11. [CrossRef]
6. Perlmutter SJ, Garvey MA, Castellanos X, Mittleman BB, Giedd J, Rapoport JL, et al. A case of pediatric autoimmune neuropsy- chiatric disorders associated with streptococcal infections. Am J Psychiatry 1998;155:1592-8.
7. Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perl- mutter S, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998;155:262-71.
8. Swedo SE, Leonard HL, Mittleman BB, Allen AJ, Rapoport JL, Dow SP, et al. Identification of children with pediatric autoim- mune neuropychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. Am J Psy- chiatry 1997;154:110-2.

9. Mercadante MT, Busatto GF, Lombroso PJ, Prado L, Rosario- Campos MC, DoValle R, et al. The pychiatric symptoms of rheu- matic fever. Am J Psychiatry 2000;157:2036-8. [CrossRef]
10. Swedo SE, Leonard HL, Schapiro MB, Casey BJ, Mannheim GB, Lenane MC, et al. Sydenham Chorea: pysical and psychological symptoms of St Vitus’s Dance. Pediatrics 1993;91:706-13.
11. Husby G, van de Rijn I, Zabriskie JB, Abdin ZH, Williams RC Jr. Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J Exp Med 1976;144:1094-110. [CrossRef]
12. Kiessling LS, Marcotte AC, Culpepper L. Antineuronal antibodies in movement disorders. Pediatrics 1993;92:39-43.
13. Morshed SA, Parveen S, Leckman JF, Mercadante MT, Bitten- court Kiss MH, Miguel EC, et al. Antibodies against neural, nucle- ar, cytoskeletal and streptococcal epitopes in children and adults with Tourette’s Syndrome, Sydenham’s Chorea, and autoimmun disorders. Biol Psychiatry 2001;50:566-77. [CrossRef]
14. Singer HS, Giuliano JD, Hansen BH, Hallet JJ, Laurino JP, Benson M, et al. Antibodies against human putamen in children with To- urette Syndrome. Neurology 1998;50:1618-24.
15. Loiselle CR, Wendlandt JT, Rohde CA, Singer HS. Antistrepto- coccal, Neuronal, and Nuclear Antibodies in Tourette Syndrome. Pediatr Neurol 2003;28:119-25. [CrossRef]
16. Abraham S, O’Gorman M, Shulman ST. Antinuclear antibodies in Sydenham’s Chorea. Adv Exp Med Biol 1997;418:153-6.
17. American Psychiatric Association: Diagnostic and Statistical Man- ual of Mental Disorders, Fourth edition. American Psychiatric As- sociation, Washington DC; 1994.
18. Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Steven- son J, et al The Yale Global Tic Severity Scale: Initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry 1989;28:566-73. [CrossRef]
19. Zaimoğlu S, Rodopman A, Sabuncuoğlu O. Yale Genel Tik Ağırlığını Derecelendirme Ölçeği’nin Güvenirlik Çalışması 5.Ulu- sal Çocuk ve Ergen Psikiyatrisi Kongresi 1995: Ankara, Türkiye.
20. Erkal GY, Arman RA, Topçuoğlu V, Fişek G, Yazgan MY. Çocuklar için Yale-Brown Obsessif Kompulsif Ölçeği Geçerlik Güvenirlik Değerlendirmesi. 12. Ulusal Çocuk ve Ergen Psikiyatri Kongresi 2002: İstanbul, Türkiye.
21. Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Henigner GR, et al. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry 1989;46:1012-6.
22. Singer HS, Loiselle CR, Lee O, Minzer K, Swedo S, Grus FH. Anti-Basal Ganglia Antibodies in PANDAS. Mov Disord 2004; 19:406-15. [CrossRef]
23. Gause C, Morris C, Vernekar S, Pardo-Villamizar C, Grados MA, Singer HS. Antineuronal antibodies in OCD: comparisons in chil- dren with OCD-only, OCD+chronic tics and OCD+PANDAS. J Neuroimmunol 2009;214:118-24. [CrossRef]
24. Müller N, Kroll B, Schwarz MJ, Riedel M, Straube A, Lütticken R, et al. Increased titers of antibodies against streptococcal M 12 and M 19 proteins in patients with Tourette Syndrome. Psychiatry Res 2001;101:187-93. [CrossRef]
25. Kiessling LS, Marcotte AC, Culpepper L. Antineuronal antibod- ies: tics and obsessive-compulsive symptoms. J Dev Behav Pedi- atr 1994;15:421-5.
26. Garvey MA, Perlmutter SJ, Allen AJ, Hamburger S, Lougee L, Leonard HL, et al. A pilot study of penicillin prophylaxis for neu- ropsychiatric exacerbations triggered by streptococcal infec- tions. Biol Psychiatry 1999;45:1564-71. [CrossRef]
27. Peterson BS, Leckman JF, Tucker D, Scahill L, Staib L, Zhang H, at al. Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention defi- cit/hyperactivity disorders. Arch Gen Psychiatry 2000;57:364-72. [CrossRef]
28. Murphy TK, Sajid M, Soto O, Shapira N, Edge P, Yang M, et al. Detecting pediatric autoimmune neuropsychiatric disorders as- sociated with streptococcus in children with obsessive-compul- sive disorder and tics. Biol Psychiatry 2004;55:61-8. [CrossRef]