Academic Scientific JournalsA critical review of PANDAS research in the context of obsessive compulsive disorder
Keywords:
OCD, immunology, PANDAS, streptococcal bacteria, autoimmune disorderAbstract
The discovery and elaboration of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is emerging from a polemical status and gaining wide recognition. Current research has proposed a specific neurological pathogenesis for the disorder. This paper connects the dominant neurobiological model of obsessive compulsive disorder (OCD) with the proposed pathogenesis and treatment of PANDAS. PANDAS presentation is described and an important early debate regarding anti-neuronal antibodies in the brain of PANDAS patients is outlined. Recent research on a specific immunological trigger for antibodies that cause a blood brain barrier breakdown will be discussed along with treatment for the disorder. Future avenues of research are discussed including a critique of the seminal studies in PANDAS pathology and treatment from the focal point of the dominant OCD model.
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References
Alvarez, J. I., Cayrol, R., & Prat, A. (2011). Disruption of central nervous system barriers in multiple sclerosis. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1812, 252–264. doi: http://dx.doi.org/10.1016/j.bbadis.2010.06.017
Bejar, R., Yasuda, R., Krugers, H., Hood, K., & Mayford, M. (2002). Transgeniccalmodulin-dependent protein kinase II activation: dose-dependent effects onsynaptic plasticity, learning, and memory. The Journal of Neuroscience, 22, 5719–5726. doi: http://dx.doi.org/10.1523/JNEUROSCI.2743-06.2006
Church, A. J., Cardoso, F., Dale, R. C., Lees, A. J., Thompson, E. J., & Giovannoni, G. (2002). Anti-basal ganglia antibodies in acute and persistent Sydenham’s chorea. Neurology, 59, 227–231. doi: http://dx.doi. org/10.1212/WNL.59.2.227
Del Casale, A., Kotzalidis, G. D., Rapinesi, C., Serata, D., Ambrosi, E., Simonetti, A., & Girardi, P. (2010). Functional neuroimaging in obsessive-compulsive disorder. Neuropsychobiology, 64, 61–85. doi: http://dx.doi.org/10.1159/000325223
Dileepan, T., Linehan, J. L., Moon, J. J., Pepper, M., Jenkins, M. K., & Cleary, P. P. (2011). Robust antigen specific th17 T cell response to group A Streptococcus is dependent on IL-6 and intranasal route of infection. PLoS Pathogens, 7. doi: http://dx.doi.org/10.1371/journal.ppat.1002252
Dileepan, T., Smith, E. D., Knowland, D., Hsu, M., Platt, M., Bittner-Eddy, P., & Agalliu, D. (2016). Group A Streptococcus intranasal infection promotes CNS infiltration by streptococcal-specific Th17 cells. The Journal of Clinical Investigation, 126,303–317. doi: http://dx.doi.org/10.1172/JCI80792
Figee, M., Wielaard, I., Mazaheri, A., & Denys, D. (2013). Neurosurgical targets for compulsivity: what can we learn from acquired brain lesions? Neuroscience & Biobehavioral Reviews, 37, 328–339. doi: http://dx.doi.org/10.1016/j.neubiorev.2013.01.005
Freyer, T., Klöppel, S., Tüscher, O., Kordon, A., Zurowski, B., Kuelz, A., ...Voderholzer, U. (2011). Frontostriatal activation in patients with obsessive-compulsive disorder before and after cognitive behavioral therapy. Psychological Medicine, 41, 207–216. doi: https://doi.org/10.1017/S0033291710000309
Giedd, J. N., Rapoport, J. L., Garvey, M. A., Perlmutter, S., & Swedo, S. E. (2000). MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection. American Journal of Psychiatry, 157, 281–283. doi: http://dx.doi.org/10.1176/appi.ajp.157.2.281
Kirvan, C. A., Swedo, S. E., Snider, L. A., & Cunningham, M. W. (2006). Antibody-mediated neuronal cell signaling in behavior and movement disorders. Journal of Neuroimmunology, 179, 173–179. doi: http://dx.doi.org/10.1016/j.jneuroim.2006.06.017
Kumar, A., Williams, M. T., & Chugani, H. T. (2015). Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and Tourette Syndrome: A positron emission tomographic (PET) study using 11C-[R]-PK11195. Journal of Child Neurology, 30, 749–756. doi: http://dx.doi.org/10.1177/0883073814543303
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry, 62, 593–602. doi: http://dx.doi.org/10.1001/archpsyc.62.6.593
Maia, T. V., & Cano-Colino, M. (2015). The role of serotonin in orbitofrontal function and obsessive-compulsive disorder. Clinical Psychological Science, 3, 460–482. doi: http://dx.doi.org/10.1177/2167702614566809
Menzies, L., Chamberlain, S. R., Laird, A. R., Thelen, S. M., Sahakian, B. J., & Bullmore, E. T. (2008). Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: The orbitofronto-striatal model revisited. Neuroscience & Biobehavioral Reviews, 32, 525–549. doi: http://dx.doi.org/10.1016/j.neubiorev.2007.09.005
Morer, A., Lázaro, L., Sabater, L., Massana, J., Castro, J., & Graus, F. (2008). Antineuronal antibodies in a group of children with obsessive–compulsive disorder and Tourette syndrome. Journal of Psychiatric Research, 42, 64–68. doi: http://dx.doi.org/10.1016/j.jpsychires.2006.09.010
Murphy, T. K., Kurlan, R., & Leckman, J. (2010). The immunobiology of Tourette’s disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: A way forward. Journal of Child and Adolescent Psychopharmacology, 20, 317–331. doi: http://dx.doi.org/10.1089/cap.2010.0043
Murphy, T. K., Parker-Athill, E. C., Lewin, A. B., Storch, E. A., & Mutch, P. J. (2015). Cefdinir for recent-onset pediatric neuropsychiatric disorders: A pilot randomized trial. Journal of Child and Adolescent Psychopharmacology, 25, 57–64. doi: http://dx.doi.org/10.1089/cap.2014.0010
Nakao, T., Okada, K., & Kanba, S. (2014). Neurobiological model of obsessive–compulsive disorder: Evidence from recent neuropsychological
and neuroimaging findings. Psychiatry and Clinical Neurosciences, 68, 587–605. doi: http://dx.doi.org/10.1111/pcn.12195
National Institute of Mental Health. (2016). Information About PANDAS. Retrieved from http://www.nimh.nih.gov/news/science-news/2015/hiv-canspread-early-evolve-in-patients-brains.shtml [accessed November 6, 2016].
Oukka, M. (2008). Th17 cells in immunity and autoimmunity. Annals of the rheumatic diseases, 67 (Suppl 3). doi: http://dx.doi.org/10.1155/2013/986789
PANDAS Network. (2012). Pediatric Acute Neuropsychiatric Symptom Scale: Parent Version. Retrieved from http://pandasnetwork.org/wp-content/uploads/2012/11/pandas_pans_scale.pdf
Pavone, P., Bianchini, R., Parano, E., Incorpora, G., Rizzo, R., Mazzone, L., & Trifiletti, R. R. (2004). Antibrain antibodies in PANDAS versus uncomplicated streptococcal infection. Pediatric neurology, 30, 107–110. doi: http://doi.org/10.1016/S0887-8994(03)00413-2
Peterson, B. S., Leckman, J. F., Tucker, D., Scahill, L., Staib, L., Zhang, H., & Lombroso, P. (2000). Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention-deficit/hyperactivity disorders.
Archives of General Psychiatry, 57, 364–372. doi: http://dx.doi.org/10.1001/archpsyc.57.4.364
Piras, F., Piras, F., Chiapponi, C., Girardi, P., Caltagirone, C., & Spalletta, G. (2015). Widespread structural brain changes in OCD: a systematic review of voxel-based morphometry studies. Cortex, 62, 89–108. doi: http://dx.doi.org/10.1016/j.cortex.2013.01.016
Radua, J., & Mataix-Cols, D. (2009). Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder. The British Journal of Psychiatry, 195, 393–402. doi: http://dx.doi.org/10.1192/bjp.bp.108.055046
Root-Bernstein, R. (2014). Rethinking molecular mimicry in rheumatic heart disease and autoimmune myocarditis: laminin, collagen IV, CAR, and B1AR as initial targets of disease. Frontiers in Pediatrics, 2, 85. doi: http://dx.doi.org/10.3389/fped.2014.00085
Rosario-Campos, M. C., Miguel, E. C., Quatrano, S., Chacon, P., Ferrao, Y., Findley, D., & Tolin, D. (2006). The Dimensional Yale–Brown Obsessive–Compulsive Scale (DY-BOCS): an instrument for assessing obsessive–compulsive symptom dimensions. Molecular Psychiatry, 11, 495–504. doi: http://doi:10.1038/sj.mp.4001798
Saxena, S., Gorbis, E., O’Neill, J., Baker, S. K., Mandelkern, M. A., Maidment, K. M., & London, E. D. (2009). Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive disorder. Molecular Psychiatry, 14,
–205. doi: http://doi:10.1038/sj.mp.4002134
Snider, L. A., Lougee, L., Slattery, M., Grant, P., & Swedo, S. E. (2005). Antibiotic prophylaxis with azithromycin or penicillin for childhood-onset neuropsychiatric disorders. Biological Psychiatry, 57, 788–792. doi: http://dx.doi.org/10.1016/j.biopsych.2004.12.035
Swedo, S. E., Leonard, H. L., Garvey, M., Mittleman, B., Allen, A. J., Perlmutter, S., ...Dubbert B. K. (1998). Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. American Journal of Psychiatry, 155, 264–271. doi: http://dx.doi.org/pdf/10.1176/ajp.155.2.264
Swedo, S. E., & Grant, P. J. (2005). Annotation: PANDAS: a model for human autoimmune disease. Journal of Child Psychology and Psychiatry, 46, 227–234. doi: http://dx.doi.org/10.1111/j.1469-7610.2004.00386.x
Swedo, S. E., Seidlitz, J., Kovacevic, M., Latimer, M. E., Hommer, R., Lougee, L., & Grant, P. (2015). Clinical presentation of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in research and community settings. Journal of Child and Adolescent Psychopharmacology, 25, 26–30. doi: http://dx.doi.org/10.1089/cap.2014.0073
Van Toorn, R., Weyers, H. H., & Schoeman, J. F. (2004). Distinguishing PANDAS from Sydenham’s chorea: case report and review of the literature. European Journal of Paediatric Neurology, 8, 211–216. doi: http://dx.doi.org/10.1016/j.ejpn.2004.03.005
Williams, K. A., Swedo, S. E., Farmer, C. A., Grantz, H., Grant, P. J., D’Souza, P., …Leckman, J. F. (2016). Randomized, controlled trial of intravenous immunoglobulin for pediatric autoimmune neuropsychiatric disorders associated with streptococcal iInfections. Journal of the American Academy of Child & Adolescent Psychiatry, 55, 860–867. doi: http://dx.doi.org/10.1016/j.jaac.2016.06.017
Windfuhr, J. P. (2016). Tonsillektomie bei PANDAS?. Laryngo-Rhino-Otologie, 95, S110-S115. doi: http://dx.doi.org/10.1055/s-0041-109592
Wong, P. H., & White, K. M. (2015). Impact of immunoglobulin therapy in pediatric disease: a review of immune mechanisms. Clinical Reviews in Allergy & Immunology, 1–12. doi: http://dx.doi.org/10.1007/s12016-015-8499-2
Wooley, J., Heyman, I., Brammer, M., Frampton, I., McGuire, P. K., & Rubia, K. (2008). Brain activation in paediatric obsessive–compulsive disorder during tasks of inhibitory control. The British Journal of Psychiatry, 192, 25–31. doi: http://dx.doi.org/10.1192/bjp.bp.107.036558
Yoo, S. Y., Roh, M. S., Choi, J. S., Kang, D. H., Ha, T. H., Lee, J. M., …Kwon, J. S. (2008). Voxel-based morphometry study of gray matter abnormalities in obsessive compulsive disorder. Journal of Korean Medical Science, 23. doi: http://dx.doi.org/10.3346/jkms.2008.23.1.24
Zurowski, B., Kordon, A., Weber-Fahr, W., Voderholzer, U., Kuelz, A. K., Freyer, T., & Hohagen, F. (2012). Relevance of orbitofrontal neurochemistry for the outcome of cognitive-behavioural therapy in patients with obsessive–compulsive disorder. European Archives of Psychiatry and Clinical Neuroscience, 262, 617–624. doi: http://10.1007/s00406-012-0304-0
