Skip to main content
NCBI home page
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2008 Jul 11;22(4):314–320. doi: 10.1002/jcla.20261

RNA from Borna disease virus in patients with schizophrenia, schizoaffective patients, and in their biological relatives

Sandra Odebrechet Vargas Nunes 1, Eiko Nakagawa Itano 2, Marla Karine Amarante 3, Edna Maria Vissoci Reiche 4, Helen Cristina Miranda 3, Carlos Eduardo Coral de Oliveira 3, Tiemi Matsuo 5, Heber Odebrechet Vargas 1, Maria Angelica Ehara Watanabe 2,✉
PMCID: PMC6649126  PMID: 18623121

Abstract

Numerous interactions of the immune system with the central nervous system have been described recently. Mood and psychotic disorders, such as severe depression and schizophrenia, are both heterogeneous disorders regarding clinical symptomatology, the acuity of symptoms, the clinical course, the treatment response, and probably also the etiology. Detection of p24 RNA from Borna disease virus (BDV) by the reverse transcriptase polymerase chain reaction in patients with schizophrenia, schizoaffective disorder, and in their biological relatives was evaluated. The subjects were 27 schizophrenic and schizoaffective patients, 27 healthy controls, 20 relatives without psychiatric disease, and 24 relatives with mood disorder, who attended the Psychiatric Ambulatory of Londrina State University, Paraná, Brazil. The subjects were interviewed by structured diagnostic criteria categorized according to the Diagnostic and Statistical Manual of Mental Disorders‐IV, axis I, (SCID‐IV). The mean duration of illness in schizophrenic and schizoaffective patients was 15.341±1.494 years and the median age at onset was 22.4±7.371 years. There were no significant differences in gender (P=0.297), age (P=0.99), albumin (P=0.26), and body mass index (kg/m2) (p=0.28), among patients, controls, and relatives. Patients and biological relatives had significantly higher positive p24 RNA BDV detection than controls (P=0.04); however, the clinical significance of BDV remains to be clarified. J. Clin. Lab. Anal. 22:314–320, 2008. © 2008 Wiley‐Liss, Inc.

Keywords: Borna disease virus, schizophrenic, schizoaffective disorder

REFERENCES

  • 1. Lewis DA, Lieberman JA. Catching up on schizophrenia: Natural history and neurobiology. Neuron 2000;28:325–334. [DOI] [PubMed] [Google Scholar]
  • 2. Mortensen PB, Pedersen CB, Westergaard T, et al. Effects of family history and place and season of birth on the risk of schizophrenia. N Engl J Med 1999;340:603–608. [DOI] [PubMed] [Google Scholar]
  • 3. Torrey EF, Yolken RH. Could schizophrenia be a viral zoonosis transmitted from house cats? Schizophr Bull 1995;21:167–171. [DOI] [PubMed] [Google Scholar]
  • 4. Torrey EF, Miller J, Rawlings R, et al. The seasonality of births in schizophrenia and bipolar disorder: A review of the literature. Schizophr Res 1997;28:1–38. [DOI] [PubMed] [Google Scholar]
  • 5. Torrey EF, Yolken RH. At issue: Is household crowding a risk factor for schizophrenia and bipolar disorder. Schizophr Bull 1998;24:321–324. [DOI] [PubMed] [Google Scholar]
  • 6. Yolken RH, Karlsson H, Yee F, Yolken RH. Endogenous retroviruses and schizophrenia. Brain Res Rev 2000;31:193–199. [DOI] [PubMed] [Google Scholar]
  • 7. Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP. Developmental neurobiology of childhood stress and trauma. Psychiatr Clin N Am 2002;25:397–426. [DOI] [PubMed] [Google Scholar]
  • 8. Spector DH. Potential host range expansion of the retroviruses. Dev Biol Stand 1992;76:153–164. [PubMed] [Google Scholar]
  • 9. Suvissari J, Mautemps N, Haukka J, Hovi T, Lönnqvist J. Childhood central nervous system viral infections and adult schizophrenia. Am J Psychiatr 2003;160:1183–1185. [DOI] [PubMed] [Google Scholar]
  • 10. Karlsson H, Bachmann S, Schroder J, McArthur J, Torrey EF, Yolken RH. Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Proc Natl Acad Sci USA 2001;98:4634–4639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. O'Reilly RL, Singh SM. Retroviruses and schizophrenia revisited. Am J Med Genet 1996;67:19–24. [DOI] [PubMed] [Google Scholar]
  • 12. Yolken R. Viruses and schizophrenia: A focus on herpes simplex virus. Herpes 2004;11:83A–88A. [PubMed] [Google Scholar]
  • 13. Albright AV, Soldan SS, Gonzalez‐Scarano F. Pathogenesis of human immunodeficiency virus‐induced neurological disease. J Neurovirol 2003;9:222–227. [DOI] [PubMed] [Google Scholar]
  • 14. Frank O, Giehl M, Zheng C, et al. Endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders. J Virol 2005;79:10890–10901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Amsterdam JD, Winokur A, Dyson W, et al. Borna Disease Virus: A possible etiologic factor in human affective disorders? Arch Gen Psychiatr 1985;42:1093–1096. [DOI] [PubMed] [Google Scholar]
  • 16. Horning M, Lipkin I. Infectious and immune factors in the pathogenesis of neurodevelopmental disorders: Epidemiology, hypotheses and animal models. Ment Retard Dev Disabil Res Rev 2001;7:200–210. [DOI] [PubMed] [Google Scholar]
  • 17. Werner‐Keišs N, Garten W, Richt JA, et al. Restricted expression of Borna disease virus glycoprotein in brains of experimentally infected Lewis rats. Neuropathol Appl Neurobiol February 14 [Epub ahead of print], 2008. [DOI] [PubMed]
  • 18. Pletnikov MV, Rubin SA, Carbone KM, Moran TH, Schwartz GJ. Neonatal Borna disease virus infection (BDV)‐induced damage to the cerebellum is associated with sensorimotor deficits in developing Lewis rats. Brain Res Dev Brain Res 2001;126: 1–12. [DOI] [PubMed] [Google Scholar]
  • 19. Dittrich W, Bode L, Ludwig H, Kao M, Schneider K. Learning deficiencies in Borna disease virus‐infected but clinically healthy rats. Biol Psychiatry 1989;26:818–828. [DOI] [PubMed] [Google Scholar]
  • 20. Tomonaga K. Virus‐induced neurobehavioral disorders: Mechanisms and implications. Trends Mol Med 2004;10:71–77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Schneider U, Schwemmle M, Staeheli P. Genome trimming: A unique strategy for replication control employed by Borna disease virus. Proc Natl Acad Sci USA 2005;102:3441–3446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Bode L, Ferszt R, Czech G. Borna disease virus infection and affective disorders in man. Arch Virol Suppl 1993;7:159–167. [DOI] [PubMed] [Google Scholar]
  • 23. Bode L, Zimmermann W, Ferszt R, Steinbach F, Ludwig H. Borna disease virus genome transcribed and expressed in psychiatric patients. Nat Med 1995;1:232–236. [DOI] [PubMed] [Google Scholar]
  • 24. Bode L, Ludwig H. Borna disease virus infection, a Human mental‐health risk. Clinic Microb Rev 2003;16:534–545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Flower R, Ludwig H. Presence of Borna disease virus (BDV)‐specific structural components in human blood plasma. J Clin Virol 2006;36:312–313. [DOI] [PubMed] [Google Scholar]
  • 26. Wolff T, Heins G, Pauli G, Burger R, Kurth R. Failure to detect Borna disease virus antigen and RNA in human blood. J Clin Virol 2006;36:309–311. [DOI] [PubMed] [Google Scholar]
  • 27. De la Torre JC. Bornavirus and the brain. J Infect Dis 2002;1;186:S241–S247. [DOI] [PubMed] [Google Scholar]
  • 28. Nakamura Y, Takahashi H, Shoya Y, et al. Isolation of Borna disease virus from human brain tissue. J Virol 2000;74: 4601–4611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. Chen CH, Chiu YL, Shaw CK, Tsai MT, Hwang AL, Hsiao KJ. Detection of Borna disease virus RNA from peripheral blood cells in schizophrenic patients and mental health workers. Mol Psychiatr 1999;4:566–571. [DOI] [PubMed] [Google Scholar]
  • 30. Taieb O, Baleyte JM, Mazet P, Fillet AM. Borna disease virus and psychiatry. Eur Psychiatry 2001;16:3–10. [DOI] [PubMed] [Google Scholar]
  • 31. Bode L, Reckwald P, Severus WE, et al. Borna disease virus–specific circulating immune complexes antigenemia, and free antibodies—the key marker triplet determining infection and prevailing in severe mood disorders. Mol Psychiatry 2001;6:481–491. [DOI] [PubMed] [Google Scholar]
  • 32. Miranda HC, Nunes SO, Calvo ES, Suzart S, Itano EN, Watanabe MA. Detection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients. J Affect Dis 2006;90:43–47. [DOI] [PubMed] [Google Scholar]
  • 33. Rothermundt M, Arolt V, Bayer T. Review of immunological and immunopathological findings in schizophrenia. Brain Behav Immun 2001;15:319–339. [DOI] [PubMed] [Google Scholar]
  • 34. Terayama H, Nishino Y, Kishi M, Ikuta K, Itoh M, Iwahashi K. Detection of anti‐Borna disease virus (BDV) antibodies from patients with schizophrenia and mood disorders in Japan. Psychiatry Res 2003;120:201–206. [DOI] [PubMed] [Google Scholar]
  • 35. Rott R, Herzog S, Fleischer B, et al. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 1985;228:755–756. [DOI] [PubMed] [Google Scholar]
  • 36. Iwahashi K Watanabe M, Nakamura K, et al. Positive and negative syndromes and Borna disease virus infection in schizophrenia. Neuropsychobiology 1998;37:59–64. [DOI] [PubMed] [Google Scholar]
  • 37. Marx CE, Jarskog LF, Lauder JM, Lieberman JA, Gilmore JH. Cytokine effects on cortical neuron MAP‐2 immunoreactivity: Implications for schizophrenia. Biol Psychiatr 2001;50:743–749. [DOI] [PubMed] [Google Scholar]
  • 38. Del‐Ben CM, Vilela JA, Crippa JAS, Hallak JEC, Labate CM, Zuardi AW. Confiabilidade da “entrevista clínica estruturada para o D.S.M.‐IV”. Rev Bras Psiquiatr 2001;23:156–159. [Google Scholar]
  • 39. Kishi M, Arimura Y, Ikuta K, Shoya Y, Lai PK, Kakinuma M. Sequence variability of Borna disease virus open reading frame II found in human peripheral blood mononuclear cells. J Virol 1996;70:635–640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Andreasen NC, Black DW. Introductory textbook of psychiatry, third edition Arlington: American Psychiatric Publishing; 2001. [Google Scholar]
  • 41. Zwick W. Handbuch der Viruskrankheiten, Vol. 2 In: Gildemeister E, Haagen E. Waldmann, O , editors. Germany: Fischer, Jena, 1939. p 254–354. [Google Scholar]
  • 42. Waelchli RO, Ehrensperger F, Metzler A, Winder C. Borna disease in a sheep. Vet Rec 1985;117:499–500. [DOI] [PubMed] [Google Scholar]
  • 43. Lundgren AL, Czech G, Bode L, Ludwig H. Natural Borna disease in domestic animals others than horses and sheep. Zentralbl Veterinarmed B 1993;40:298–303. [DOI] [PubMed] [Google Scholar]
  • 44. Malkinson M, Weisman Y, Ashash E, Bode L, Ludwig H. Borna disease in ostriches.Vet Rec 1993;133:304. [DOI] [PubMed] [Google Scholar]
  • 45. Sprankel H, Richarz K, Ludwig H, Rott R. Behavior alterations in tree shrews (Tupaia glis, Diard 1820) induced by Borna disease virus. Med Microbiol Immunol 1978;165:1–18. [DOI] [PubMed] [Google Scholar]
  • 46. Stitz L, Krey H, Ludwig H. Borna disease in rhesus monkeys as a model for uveo‐cerebral symptoms. J Med Virol 1981;6: 333–340. [DOI] [PubMed] [Google Scholar]
  • 47. Fu ZF, Amsterdam JD, Kao M, Shankar V, Koprowski H, Dietzschold B. Detection of Borna disease virus‐reactive antibodies from patients with affective disorders by western immunoblot technique. J Affect Disord 1993;27:61–68. [DOI] [PubMed] [Google Scholar]
  • 48. Briese T, Schneemann A, Lewis AJ, et al. Genomic organization of Borna disease virus. Proc Natl Acad Sci USA 1994;91: 4362–4366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Porombka D, Baumgärtner W, Herden C. A rapid method for gene expression analysis of Borna disease virus in neurons and astrocytes using laser microdissection and real‐time RT‐PCR. J Virol Methods 2008;148:58–65. [DOI] [PubMed] [Google Scholar]
  • 50. Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: On the matter of their convergence. Molec Psych 2005;10:40–68. [DOI] [PubMed] [Google Scholar]
  • 51. Andreasen NC. Brave New Brain. Oxford: Oxford University Press, 2001. p 35–36. [Google Scholar]
  • 52. Nunes SO, Borelli SD, Matsuo T, Watanabe MA, Itano EN. The association of the HLA in patients with schizophrenia, schizoaffective disorder, and in their biological relatives. Schizophr Res 2005;76:195–198. [DOI] [PubMed] [Google Scholar]
  • 53. Nunes SO, Matsuo T, Kaminami MS, Watanabe MA, Reiche EM, Itano EN. An autoimmune or an inflammatory process in patients with schizophrenia, schizoaffective disorder, and in their biological relatives. Schizophr Res 2006;84:180–182. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES