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Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2020, Number 4

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Salud Mental 2020; 43 (4)

Association of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci

Genis-Mendoza AD, Nicolini H, Manrique V, López-Canovas L, Cabrera-Mendoza B, Bobes MA, Lanzagorta N, Santana D

Language: English
References: 35
Page: 181-187
PDF size: 384.18 Kb.


ABSTRACT

Introduction. It has been hypothesized that pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) etiology results from an abnormal immune response to streptococcal infection. There is evidence that the serotonergic system is involved in both obsessive-compulsive disorder (OCD) physiopathology and immunological processes. In the 5’ promoter region of 5-HTT, gene encoding for the serotonin transporter we can find the 5-HTTLPR polymorphism that has been associated with OCD. Being PANDAS a disorder with OCD symptoms and likely immune abnormalities, 5-HTT polymorphisms may be particularly relevant for this disorder. Objective. This study aimed to test the association between the 5-HT genotypes and the presence of serum antibodies in patients with PANDAS. Method. We compared the genotype frequencies and serum anti-streptococcal, anti-neural, and anti-enolase antibodies titers between 56 patients with PANDAS and 20 healthy controls from Mexico and Cuba. Results. Antibody titers were higher (anti-enolase, anti-streptococcal) in PANDAS patients compared to healthy controls. No differences in anti-neural antibody levels between both groups were detected. The anti-enolase and anti-neural antibody titer increased according to the polymorphism of the PANDAS patients as follows: LL ›SL ›SS. Discussion and conclusion. This is the first study evaluating the association between the 5-HTTLPR genotypes and antibody titers in PANDAS patients. Associations between polymorphisms in serotonergic genes and immune response could provide valuable information about the interaction between both systems. Our results suggest an association between the S allele and elevated antibody levels in PANDAS patients.


REFERENCES

  1. Ahern, G. P. (2011). 5-HT and the immune system. Current Opinion in Pharmacology, 11(1), 29-33. doi: 10.1016/j.coph.2011.02.004

  2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®). Washington, DC: American Psychiatric Publishing, Inc.

  3. Bastani, B., Arora, R. C., & Meltzer, H. Y. (1991). Serotonin uptake and imipramine binding in the blood platelets of obsessive-compulsive disorder patients. Biological Psychiatry, 30(2), 131-139. doi: 10.1016/0006-3223(91)90166-J

  4. Bengel, D., Greenberg, B. D., Corá-Locatelli, G., Altemus, M., Heils, A., Li, Q., & Murphy, D. L. (1999). Association of the serotonin transporter promoter regulatory region polymorphism and obsessive-compulsive disorder. Molecular Psychiatry, 4(5), 463-466. doi: 10.1038/sj.mp.4000550

  5. Billett, E. A., Richter, M. A., King, N., Heils, A., Lesch, K. P., & Kennedy, J. L. (1997). Obsessive compulsive disorder, response to serotonin reuptake inhibitors and the serotonin transporter gene. Molecular Psychiatry, 2(5), 403- 406. doi: 10.1038/sj.mp.4000257

  6. Cabrera-Mendoza, B., Genis-Mendoza, A. D., & Nicolini, H. (2019). Diagnosis in PANDAS: An update. Current Psychiatry Research and Reviews, 15(4), 237- 247. doi: 10.2174/2666082215666190917161514

  7. Camarena, B., Rinetti, G., Cruz, C., Hernández, S., de la Fuente, J. R., & Nicolini, H. (2001). Association study of the serotonin transporter gene polymorphism in obsessive–compulsive disorder. International Journal of Neuropsychopharmacology, 4(3), 269-272. doi: 10.1017/S1461145701002516

  8. Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., ... Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT Gene. Science, 301(5631), 386-389. doi: 10.1126/ science.1083968

  9. Caspi, A., Vishne, T., Sasson, Y., Gross, R., Livne, A., & Zohar, J. (2008). Relationship between childhood sexual abuse and obsessive-compulsive disorder: Case control study. Israel Journal of Psychiatry and Related Sciences, 45(3), 177- 182.

  10. Contreras, J., Hernández, S., Quezada, P., Dassori, A., Walss-Bass, C., Escamilla, M., & Raventos, H. (2010). Association of serotonin transporter promoter gene polymorphism (5-HTTLPR) with depression in Costa Rican schizophrenic patients. Journal of Neurogenetics, 24(2), 83-89. doi: 10.3109/01677060903583994

  11. Gudayol-Ferré, E., Herrera-Guzmán, I., Camarena, B., Cortés-Penagos, C., Herrera- Abarca, J. E., Martínez-Medina, P., … Guàrdia-Olmos, J. (2010). The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder. Journal of Affective Disorders, 127(1-3), 343-351. doi: 10.1016/j.jad.2010.06.002

  12. Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., & Lesch, K. P. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66(6), 2621-2624. doi: 10.1046/j.1471- 4159.1996.66062621.x

  13. Hu, X., Lipsky, R. H., Zhu, G., Akhtar, L. A., Taubman, J., Greenberg, B. D., … Goldman, D. (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. The American Journal of Human Genetics, 78(5), 815-826. doi: 10.1086/503850

  14. Jaiswal, P., Mohanakumar, K. P., & Rajamma, U. (2015). Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders. Neuroscience & Biobehavioral Reviews, 55, 413-431. doi: 10.1016/j.neubiorev.2015.05.013

  15. Lin, P. (2007). Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive–compulsive disorder. Progress in Neuro- Psychopharmacology and Biological Psychiatry, 31(3), 683-689. doi: 10.1016/j.pnpbp.2006.12.024

  16. Mak, L., Streiner, D. L., & Steiner, M. (2015). Is serotonin transporter polymorphism (5-HTTLPR) allele status a predictor for obsessive-compulsive disorder? A meta-analysis. Archives of Women’s Mental Health, 18(3), 435-445. doi: 10.1007/s00737-015-0526-z

  17. Marazziti, D., Mucci, F., & Fontenelle, L. F. (2018). Immune system and obsessivecompulsive disorder. Psychoneuroendocrinology, 93, 39-44. doi: 10.1016/j. psyneuen.2018.04.013

  18. Margoob, M. A., & Mushtaq, D. (2011). Serotonin transporter gene polymorphism and psychiatric disorders: Is there a link? Indian Journal of Psychiatry, 53(4), 289-299. doi: 10.4103/0019-5545.91901

  19. Matsunaga, H., Maebayashi, K., & Kiriike, N. (2008). A review of the researches focusing on the heterogeneity of obsessive-compulsive disorder and its potential subtypes. Seishin Shinkeigaku Zasshi = Psychiatria Et Neurologia Japonica, 110(3), 161-174.

  20. Mössner, R., & Lesch, K. P. (1998). Role of serotonin in the immune system and in neuroimmune interactions. Brain, Behavior, and Immunity, 12(4), 249-271. doi: 10.1006/brbi.1998.0532

  21. Moya, P. R., Wendland, J. R., Rubenstein, L. M., Timpano, K. R., Heiman, G. A., Tischfield, J. A., … Murphy, D. L. (2013). Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette’s disorder. Movement Disorders, 28(9), 1263-1270. doi: 10.1002/mds.25460

  22. Nicholson, T. R. J., Ferdinando, S., Krishnaiah, R. B., Anhoury, S., Lennox, B. R., Mataix-Cols, D., … Heyman, I. (2012). Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: Cross-sectional study. British Journal of Psychiatry, 200(5), 381-386. doi: 10.1192/bjp.bp.111.092007

  23. Nicolini, H., Cruz, C., Camarena, B., Páez, F., & de la Fuente, J. R. (1999). Understanding the genetic basis of obsessive-compulsive disorder. CNS Spectrums, 4(5), 32-34. doi: 10.1017/S1092852900011706

  24. Nicolini, H., Herrera, K., Páez, F., de Carmona, M. S., Orozco, B., Lodeiro, G., & de la Fuente, J. R. (1996). Traducción al español y confiabilidad de la Escala Yale-Brown para el trastorno obsesivo-compulsivo. Salud Mental, 19(3), 13-16.

  25. Nicolini, H., López, Y., Genis-Mendoza, A. D., Manrique, V., Lopez-Canovas, L., Niubo, E., … Santana, D. (2015). Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders. Actas Españolas de Psiquiatria, 43(2), 35-41.

  26. O’Connell, P. J., Wang, X., Leon-Ponte, M., Griffiths, C., Pingle, S. C., & Ahern, G. P. (2006). A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells. Blood, 107(3), 1010-1017. doi: 10.1182/blood-2005-07-2903

  27. Orefici, G., Cardona, F., Cox, C. J., & Cunningham, M. W. (2016). Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). In: Ferretti J. J, Stevens D. L, Fischetti V. A, (Ed.). Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]. Oklahoma City (OK): University of Oklahoma Health Sciences Center.

  28. Perez, M., Brown, J. S., Vrshek-Schallhorn, S., Johnson, F., & Joiner Jr, T. E. (2006). Differentiation of obsessive-compulsive-, panic-, obsessive-compulsive personality-, and non-disordered individuals by variation in the promoter region of the serotonin transporter gene. Journal of Anxiety Disorders, 20(6), 794-806. doi: 10.1016/j.janxdis.2005.09.001

  29. Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. C. (1998). The Mini-International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry, 59(Suppl 20), 22-33.

  30. Sheehan, D. V., Sheehan, K. H., Shytle, R. D., Janavs, J., Bannon, Y., Rogers, J. E., … Wilkinson, B. (2010). Reliability and validity of the mini international neuropsychiatric interview for children and adolescents (MINI-KID). The Journal of Clinical Psychiatry, 71(03), 313-326. doi: 10.4088/JCP.09m05305whi

  31. Singer, H. S., Mascaro-Blanco, A., Alvarez, K., Morris-Berry, C., Kawikova, I., Ben-Pazi, H., … Cunningham, M. W. (2015). Neuronal antibody biomarkers for Sydenham’s chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection. PloS One, 10(3), e0120499. doi: 10.1371/ journal.pone.0120499

  32. Sinopoli, V. M., Burton, C. L., Kronenberg, S., & Arnold, P. D. (2017). A review of the role of serotonin system genes in obsessive-compulsive disorder. Neuroscience & Biobehavioral Reviews, 80, 372-381. doi: 10.1016/j.neubiorev.2017.05.029

  33. 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(4), 907-911. doi: 10.1542/peds.113.4.907

  34. Ulloa, R. E., De la Peña, F., Higuera, F., Palacios, L., Nicolini, H., & Ávila, J. (2004). Estudio de validez y confiabilidad de la versión en español de la Escala Yale- Brown del trastorno obsesivo-compulsivo para niños y adolescentes. Actas Españolas de Psiquiatría, 32(4), 216-221.

  35. Zhang, Y. W., Gesmonde, J., Ramamoorthy, S., & Rudnick, G. (2007). Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder. Journal of Neuroscience, 27(40), 10878-10886. doi: 10.1523/JNEUROSCI.0034-07.2007




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