Skip to main content Accessibility help
×
×
Home

Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study

  • Timothy R. J. Nicholson (a1), Sumudu Ferdinando (a2), Ravikumar B. Krishnaiah (a3), Sophie Anhoury (a1), Belinda R. Lennox (a4), David Mataix-Cols (a1), Anthony Cleare (a1), David M. Veale (a1), Lynne M. Drummond (a2), Naomi A. Fineberg (a3), Andrew J. Church (a5), Gavin Giovannoni (a6) and Isobel Heyman (a7)...

Abstract

Background

Symptoms of obsessive–compulsive disorder (OCD) have been described in neuropsychiatric syndromes associated with streptococcal infections. It is proposed that antibodies raised against streptococcal proteins cross-react with neuronal proteins (antigens) in the brain, particularly in the basal ganglia, which is a brain region implicated in OCD pathogenesis.

Aims

To test the hypothesis that post-streptococcal autoimmunity, directed against neuronal antigens, may contribute to the pathogenesis of OCD in adults.

Method

Ninety-six participants with OCD were tested for the presence of anti-streptolysin-O titres (ASOT) and the presence of anti-basal ganglia antibodies (ABGA) in a cross-sectional study. The ABGA were tested for with western blots using three recombinant antigens; aldolase C, enolase and pyruvate kinase. The findings were compared with those in a control group of individuals with depression (n = 33) and schizophrenia (n = 17).

Results

Positivity for ABGA was observed in 19/96 (19.8%) participants with OCD compared with 2/50 (4%) of controls (Fisher's exact test P = 0.012). The majority of positive OCD sera (13/19) had antibodies against the enolase antigen. No clinical variables were associated with ABGA positivity. Positivity for ASOT was not associated with ABGA positivity nor found at an increased incidence in participants with OCD compared with controls.

Conclusions

These findings support the hypothesis that central nervous system autoimmunity may have an aetiological role in some adults with OCD. Further study is required to examine whether the antibodies concerned are pathogenic and whether exposure to streptococcal infection in vulnerable individuals is a risk factor for the development of OCD.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study
      Available formats
      ×

Copyright

Corresponding author

Tim Nicholson, Section of Cognitive Neuropsychiatry, Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF. Email: timothy.nicholson@kcl.ac.uk

Footnotes

Hide All

See editorial, pp. 353–355, this issue.

The South London & Maudsley NHS Foundation Trust, the Institute of Psychiatry, London, and the Department of Neuroinflammation, Institute of Neurology, London.

Declaration of interest

None.

Footnotes

References

Hide All
1 Radua, J, Mataix-Cols, D. Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder. Br J Psychiatry 2009; 195: 393402.
2 de Koning, PP, Figee, M, van den Munckhof, P, Schuurman, PR, Denys, D. Current status of deep brain stimulation for obsessive-compulsive disorder: a clinical review of different targets. Curr Psychiatry Rep 2011; 13: 274–82.
3 Guehl, D, Benazzouz, A, Aouizerate, B, Cuny, E, Rotge, JY, Rougier, A, et al. Neuronal correlates of obsessions in the caudate nucleus. Biol Psychiatry 2008; 63: 557–62.
4 Cavedini, P, Gorini, A, Bellodi, L. Understanding obsessive-compulsive disorder: focus on decision making. Neuropsychol Rev 2006; 16: 315.
5 Stein, DJ, Fineberg, NA, Bienvenu, OJ, Denys, D, Lochner, C, Nestadt, G, et al. Should OCD be classified as an anxiety disorder in DSM-V? Depress Anxiety 2010; 27: 495506.
6 Asbahr, FR, Negrao, AB, Gentil, V, Zanetta, DM, da Paz, JA, Marques-Dias, MJ, et al. Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study. Am J Psychiatry 1998; 155: 1122–4.
7 Martino, D, Giovannoni, G. Antibasal ganglia antibodies and their relevance to movement disorders. Curr Opin Neurol 2004; 17: 425–32.
8 Church, AJ, Cardoso, F, Dale, RC, Lees, AJ, Thompson, EJ, Giovannoni, G. Anti-basal ganglia antibodies in acute and persistent Sydenham's chorea. Neurology 2002; 59: 227–31.
9 Edwards, MJ, Trikouli, E, Martino, D, Bozi, M, Dale, RC, Church, AJ, et al. Anti-basal ganglia antibodies in patients with atypical dystonia and tics: a prospective study. Neurology 2004; 63: 156–8.
10 Church, AJ, Dale, RC, Lees, AJ, Giovannoni, G, Robertson, MM. Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry 2003; 74: 602–7.
11 Dale, RC, Church, AJ, Surtees, RA, Lees, AJ, Adcock, JE, Harding, B, et al. Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. Brain 2004; 127: 2133.
12 Swedo, SE, Leonard, HL, Garvey, M, Mittleman, B, Allen, AJ, Perlmutter, S, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998; 155: 264–71.
13 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). APA, 1994.
14 Dale, RC, Heyman, I, Giovannoni, G, Church, AWJ. Incidence of anti-brain antibodies in children with obsessive–compulsive disorder. Br J Psychiatry 2005; 187: 314–9.
15 Foa, EB, Huppert, JD, Leiberg, S, Langner, R, Kichic, R, Hajcak, G, et al. The Obsessive-Compulsive Inventory: development and validation of a short version. Psychol Assess 2002; 14: 485–96.
16 Goodman, WK, Price, LH, Rasmussen, SA, Mazure, C, Fleischmann, RL, Hill, CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 1989; 46: 1006–11.
17 Montgomery, SA, Åsberg, M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–9.
18 Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59 (suppl 20): 2233.
19 Dale, RC, Candler, PM, Church, AJ, Wait, R, Pocock, JM, Giovannoni, G. Neuronal surface glycolytic enzymes are autoantigen targets in post-streptococcal autoimmune CNS disease. J Neuroimmunol 2006; 172: 187–97.
20 Leckman, JF, Grice, DE, Boardman, J, Zhang, H, Vitale, A, Bondi, C, et al. Symptoms of obsessive-compulsive disorder. Am J Psychiatry 1997; 154: 911–7.
21 Bloch, MH, Landeros-Weisenberger, A, Rosario, MC, Pittenger, C, Leckman, JF. Meta-analysis of the symptom structure of obsessive-compulsive disorder. Am J Psychiatry 2008; 165: 1532–42.
22 Morer, A, Lazaro, L, Sabater, L, Massana, J, Castro, J, Graus, F. Antineuronal antibodies in a group of children with obsessive-compulsive disorder and Tourette syndrome. J Psychiatr Res 2008; 42: 64–8.
23 Gause, C, Morris, C, Vernekar, S, Pardo-Villamizar, C, Grados, MA, Singer, HS. Antineuronal antibodies in OCD: comparisons in children with OCD-only, OCD+chronic tics and OCD+PANDAS. J Neuroimmunol 2009; 214: 118–24.
24 Maina, G, Albert, U, Bogetto, F, Borghese, C, Berro, AC, Mutani, R, et al. Anti-brain antibodies in adult patients with obsessive-compulsive disorder. J Affect Disord 2009; 116: 192200.
25 Bhattacharyya, S, Khanna, S, Chakrabarty, K, Mahadevan, A, Christopher, R, Shankar, SK. Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder. Neuropsychopharmacology 2009; 34: 2489–96.
26 Kirvan, CA, Swedo, SE, Kurahara, D, Cunningham, MW. Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham's chorea. Autoimmunity 2006; 39: 21–9.
27 Kansy, JW, Katsovich, L, McIver, KS, Pick, J, Zabriskie, JB, Lombroso, PJ, et al. Identification of pyruvate kinase as an antigen associated with Tourette syndrome. J Neuroimmunol 2006; 181: 165–76.
28 Murphy, TK, Kurlan, R, Leckman, J. The immunobiology of Tourette's disorder, pediatric autoimmune neuropsychiatric disorders associated with streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol 2010; 20: 317–31.
29 Martino, D, Church, A, Giovannoni, G. Are antibasal ganglia antibodies important, and clinically useful? Pract Neurol 2007; 7: 3241.
30 Atassi, MZ, Casali, P. Molecular mechanisms of autoimmunity. Autoimmunity 2008; 41: 123–32.
31 Westenberg, HG, Fineberg, NA, Denys, D. Neurobiology of obsessive-compulsive disorder: serotonin and beyond. CNS Spectr 2007; 12 (suppl 3): 1427.
32 Yaddanapudi, K, Hornig, M, Serge, R, De Miranda, J, Baghban, A, Villar, G, et al. Passive transfer of streptococcus-induced antibodies reproduces behavioral disturbances in a mouse model of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Mol Psychiatry 2010; 15: 712–26.
33 Johnson, DR, Kurlan, R, Leckman, J, Kaplan, EL. The human immune response to streptococcal extracellular antigens: clinical, diagnostic, and potential pathogenetic implications. Clin Infect Dis 2010; 50: 481–90.
34 Perlmutter, SJ, Leitman, SF, Garvey, MA, Hamburger, S, Feldman, E, Leonard, HL, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet 1999; 354: 1153–8.
35 Snider, LA, Lougee, L, Slattery, M, Grant, P, Swedo, SE. Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biol Psychiatry 2005; 57: 788–92.
36 Garvey, MA, Perlmutter, SJ, Allen, AJ, Hamburger, S, Lougee, L, Leonard, HL, et al. A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections. Biol Psychiatry 1999; 45: 1564–71.
37 Storch, EA, Murphy, TK, Geffken, GR, Mann, G, Adkins, J, Merlo, LJ, et al. Cognitive-behavioral therapy for PANDAS-related obsessive-compulsive disorder: findings from a preliminary waitlist controlled open trial. J Am Acad Child Adolesc Psychiatry 2006; 45: 1171–8.
38 de Oliveira, SK, Pelajo, CF. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS): a controversial diagnosis. Curr Infect Dis Rep 2010; 12: 103–9.
39 Zandi, MS, Irani, SR, Lang, B, Waters, P, Jones, PB, McKenna, P, et al. Disease-relevant autoantibodies in first episode schizophrenia. J Neurol 2011; 258: 686–8.
40 Brilot, F, Merheb, V, Ding, A, Murphy, T, Dale, RC. Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome. Neurology 2011; 76: 1508–13.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study

  • Timothy R. J. Nicholson (a1), Sumudu Ferdinando (a2), Ravikumar B. Krishnaiah (a3), Sophie Anhoury (a1), Belinda R. Lennox (a4), David Mataix-Cols (a1), Anthony Cleare (a1), David M. Veale (a1), Lynne M. Drummond (a2), Naomi A. Fineberg (a3), Andrew J. Church (a5), Gavin Giovannoni (a6) and Isobel Heyman (a7)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *