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Incidence of anti-brain antibodies in children with obsessive–compulsive disorder

  • Russell C. Dale (a1), Isobel Heyman (a2), Gavin Giovannoni (a3) and Andrew J. Church (a3)
Abstract
Background

Obsessions and compulsions may occur in the post-streptococcal disorders Sydenham's chorea and paediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS). The proposed mediators are anti-basal ganglia antibodies (ABGA)

Aims

We tested the hypothesis that post-streptococcal autoimmunity may have a role in ‘idiopathic’ obsessive–compulsive disorder (OCD)

Method

We examined 50 children with OCD for ABGA using enzyme-linked immunosorbent assay (ELISA) and western immunoblotting. The findings were compared with paediatric autoimmune (n=50), neurological (n=100) and streptococcal (n=40) controls.

Results

The mean ABGA binding on ELISA was elevated in the patient cohort compared with all control groups (P<0.005 in all comparisons). Western immunoblotting revealed positive antibody binding (as seen in Sydenham's chorea) in 42% of the patient cohort compared with 2–10% of control groups (P<0.001 in all comparisons)

Conclusions

Our findings support the hypothesis that central nervous system autoimmunity may have a role in a significant subgroup of cases of OCD. Further study is required to examine whether the antibodies concerned are pathogenic.

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Copyright
Corresponding author
Dr Isobel Heyman, Department of Child and Adolescent Psychiatry, PO Box 085, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. E-mail: I.Heyman@iop.kcl.ac.uk
Footnotes
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Declaration of interest

None. Funding detailed in Acknowledgements.

Footnotes
References
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American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). Washington, DC: APA.
Asbahr, F. R., Ramos, R. T., Negrao, A. B., et al (1999) Case series: increased vulnerability to obsessive–compulsive symptoms with repeated episodes of Sydenham chorea. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 15221525.
Church, A. J., Cardoso, F., Dale, R. C., et al (2002) Anti-basal ganglia antibodies in acute and persistent Sydenham's chorea. Neurology, 59, 227231.
Church, A. J., Dale, R. C., Cardoso, F., et al (2003a) CSF and serum immune parameters in Sydenham's chorea: evidence of an autoimmune syndrome? Journal of Neuroimmunology, 136, 149153.
Church, A. J., Dale, R. C., Lees, A. J., et al (2003b) Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis. Journal of Neurobiology, Neurosurgery and Psychiatry, 74, 602607.
Dale, R. C., Church, A. J., Surtees, R. A., et al (2004) Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. Brain, 127, 2133.
Giedd, J. N., Rapoport, J. L., Kruesi, M. J., et al (1995) Sydenham's chorea: magnetic resonance imaging of the basal ganglia. Neurology, 45, 21992202.
Hallett, J. J., Harling-Berg, C. J., Knopf, P. M., et al (2000) Anti-striatal antibodies in Tourette syndrome cause neuronal dysfunction. Journal of Neuroimmunology, III, 195202.
Hoekstra, P. J., Horst, G., Limburg, P. C., et al (2003) Increased seroreactivity in tic disorder patients to a 60 kDa protein band from a neuronal cell line. Journal of Neuroimmunology, 141, 118124.
Husby, G., van de Rijn, I., Zabriskie, J. B., et al (1976) Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. Journal of Experimental Medicine, 144, 10941110.
Kiessling, L. S., Marcotte, A. C. & Culpepper, L. (1993) Antineuronal antibodies in movement disorders. Pediatrics, 92, 3943.
Kiessling, L. S., Marcotte, A. C. & Culpepper, L. (1994) Antineuronal antibodies: tics and obsessive–compulsive symptoms. Journal of Developmental and Behavioural Pediatrics, 15, 421425.
Kirvan, C. A., Swedo, S. E., Heuser, J. S., et al (2003) Mimicry and autoantibody-mediated neuronal cell signalling in Sydenham chorea. Nature Medicine, 9, 914920.
Kurlan, R. & Kaplan, E. L. (2004) The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive–compulsive symptoms; hypothesis or entity? Practical considerations for the clinician. Pediatrics, 113, 883886.
Mercadante, M. T., Busatto, G. F., Lombroso, P. J., et al (2000) The psychiatric symptoms of rheumatic fever. American Journal of Psychiatry, 157, 20362038.
Murphy, T. K., Goodman, W. K., Fudge, M. W., et al (1997) B lymphocyte antigen D8/I7: a peripheral marker for childhood-onset obsessive–compulsive disorder and Tourette's syndrome? American Journal of Psychiatry, 154, 402407.
Pauls, D. L., Alsobrook, J. P., Goodman, W., et al (1995) A family study of obsessive–compulsive disorder. American Journal of Psychiatry, 152, 7684.
Perlmutter, S. J., Leitman, S. F., Garvey, M. A., et al (1999) Therapeutic plasma exchange and intravenous immunoglobulin for obsessive–compulsive disorder and tic disorders in childhood. Lancet, 354, 11531158.
Scahill, L., Riddle, M. A., McSwiggin-Hardin, M., et al (1997) Children's Yale–Brown Obsessive Compulsive Scale: reliability and validity. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 844852.
Spaun, J., Bentzon, M. W., Olesen Larsen, S., et al (1961) International standard for antistreptolysin O. Bulletin of the World Health Organization, 24, 271279.
Stein, D. J. (2002) Obsessive–compulsive disorder. Lancet, 360, 397405.
Swedo, S. E., Leonard, H. L., Garvey, M., et al (1998) Pediatric autoimmune neuropsychatric disorders associated with streptococcal infections: clinical description of the first 50 cases. American Journal of Psychiatry, 155, 264271.
Swedo, S. E., Leonard, H. L. & Rapoport, J. L. (2004) The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics, 113, 907911.
Von Economo, C. (1931) Encephalitis Lethargica: Its Sequelae and Treatment (transl. Newman, K. O.). Oxford: Oxford University Press.
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Incidence of anti-brain antibodies in children with obsessive–compulsive disorder

  • Russell C. Dale (a1), Isobel Heyman (a2), Gavin Giovannoni (a3) and Andrew J. Church (a3)
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eLetters

Antiphosphatidylethanoline Antibody in a PANDAS-Like Condition

Deborah K. Sokol, Associate Professor; Pediatric Neurologist
12 April 2006

Dear Editor,

We read with great interest the investigation of RC Dale, et al. on the incidence of anti-brain antibodies in children with obsessive-compulsive disorder (1). In this study, high levels of anti-basal gangliaantibodies (ABGA) were found in serum from children with obsessive compulsive disorder (OCD) as compared to control groups of children with streptococcal infection without OCD, pediatric autoimmune disease and neurological disorders (stroke, movement disorders and encephalitis). These investigators concluded that central nervous system autoimmunity mayplay a role in a significant subgroup of children with OCD.

Recently, we found another autoantibody, antiphosphatidylethanolamine(aPE), which may be associated with explosive onset of OCD in a five-year old girl. Six weeks prior to showing OCD symptoms, the girl was diagnosedwith an ear infection, for which she received a full course of antibiotics. She presented at our clinic two months after the onset of OCD symptoms. Past medical history was significant for recurrent ear infection. Physical and neurologic examinations were normal; no tics wereobserved. There was no family history of OCD.

At the index visit, the patient was negative for streptolysin O antibody. Throat cultures were negative for Streptococcus pyogenes and Streptococcus group A antigen. A test for deoxyribonuclease B, a marker for prior streptococcus infection, was negative.

To investigate an autoimmune diathesis, the patient was tested for IgG, IgA and IgM aPE, antiphosphatidylserine (aPS), antiphosphatidylcholine (aPC) and anticardiolipin (aCL) (2). Serial antiphospholipid antibody (aPL) testing revealed persistent presence of IgG aPE antibodies (Table 1). The aPE antibody levels fluctuated coincident with the expression of her OCD symptoms. The index and day 113sera were also positive for IgG aPS. The patient was begun on a low dose of sertraline and her OCD improved.

We believe this patient has a PANDAS-like condition because the criteria, except for evidence of group A streptococcus infection, was met.With a history of repeated ear infections, her OCD symptoms occurred afterthe most recent ear infection. Without documenting the infectious agent, our patient mounted an autoimmune reaction suggested by elevated levels aPE antibody and the development of OCD after another ear infection.

We have found aPE in other neuropsychiatric conditions. We reported the case of an adolescent girl with a basal ganglia stroke who had IgA aPEin her serum and IgG and IgA aPE in her cerebral spinal fluid (CSF). Subsequent to the stroke the patient experienced seizures and depression (2). Further, aPE was the most frequently detected antiphospholipid antibody in the serum of psychotic patients (3). Thirty three percent of CSF collected from this group of psychotic patients contained IgG aPE in the absence of this particular autoantibody reactivity in serum suggestingintrathecal synthesis of the aPE antibody. We propose that aPE may attack the basal ganglia leading to its association with OCD and other disorders of the brain.

Although the finding of aPE antibodies with OCD is in a single patient, we believe, that aPE may be an additional autoimmune marker that should be considered with post-infectious OCD.

We have no interests that would be forwarded by publication of this letter.

References

1.Dale, RC, Heyman, I, Giovannoni, G and Church, AJ. Incidence of anti-brain antibodies in children with obsessive-compulsive disorder. British Journal of Psychiatry, 2005; 187: 314-319.

2.Sokol, DK, McIntyre, JA, Short, RA, Gutt, J., Wagenknecht, DR, Biller, J., Garg, B. Henoch-Schonlein purpura and stroke: antiphosphatidylethanolamine antibody in CSF and serum. Neurology, 2000; 55: 1379-1381.

3.O'Brien, R.S., Sokol, D.K., Wagenknecht, D.R., Rao. T.V. and McIntyre, J.A. Antiphospholipid antibody (APL) in serum and CSF from patients with psychosis. Thromb Research, 2004; 114:629.

4.McIntyre JA, Wagenknecht DR, Waxman DW. Frequencies and specificities of antiphospholipid antibodies (aPL) in volunteer blood donors. Immunobiology 2003;207:59-63
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Conflict of interest: None Declared

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