Can We Determine High Risk Groups in Schizophrenia? A Hypothesis

Abstract

Neurodevelopmental hypothesis suggested that schizophrenia is a disorder of early brain development, in which the brain structural abnormalities are present. The causes of the abnormal processes remains unclear however, Genetics vulnerability, obstetric complications and viral infections have been shown to play a role in this disorder. Several studies have shown a greater incidence of winter or spring births in patients. Prenatal and perinatal infections, especially in the second trimester of pregnancy, have been considered a plausible risk factor for schizophrenia. Maternal exposure to influenza, herpes viruses, varicella zoster virus, Epstein-Barr virus, cytomegalovirus and rarely rubella virus infections confers an increased risk of schizophrenia to the developing offspring. As clinicians, we observed that our patients with psychotic disorder were not exposed to the viral infections even during epidemic. We hypothesized that perinatal viral infections have been associated with lifelong immunity to this infectious diseases which on the other hand cause an increased risk of developing schizophrenia. If we could determine antibodies against these viruses among patients with schizophrenia, perhaps we will be able to identify accurate markers heralding psychotic illness as well as can use these markers in a large population-based sample.

Keywords

• Schizophrenia, viral infections, biological marker

Şizofrenide Yüksek Risk Gruplarını Belirleyebilir miyiz? Bir Hipotez

Öz

Nörogelişimsel varsayım şizofreninin beynin gelişimi sırasında oluşmaya başlayan bir bozukluk olduğunu ileri sürer. Şizofreniye neden olan hatalı gelişime ilişkin etiyolojik faktörler tam olarak bilinmemekle beraber kanıtlar genetik yatkınlık, viral enfeksiyonlar, gebelik ve doğum komplikasyonlarının önemli bir rol oynadığını göstermektedir. Bazı çalışmalarda geç kış ya da bahar aylarında doğanlarda daha fazla şizofreni hastalığı olduğu bildirilmiştir. Merkezi sinir sistemine etkisi olan virüslerin özellikle ikinci trimesterde geçirildiklerinde şizofreni etiyolojisinde rol oynadıkları düşünülmektedir. Klinisyenler olarak biz psikotik hastalarımızda epidemi zamanlarında bile viral kökenli enfeksiyon hastalıklarına yakalanmadıklarını gözlemledik. Perinatal dönemde geçirilen bu viral enfeksiyonların bir yandan kişiyi bağışık hale getirirken diğer yadan da şizofreniye yatkın hale getirdiği hipotezini savunmaktayız. Eğer genel olarak viral patojenlere karşı gelişen antikorları şizofreni hastalarında ele alıp değerlendirebilirsek, belki de hastalığın habercisi olan bir biyolojik belirteç bulabilir ve bunu geniş örneklem gruplarında kullanabiliriz.

Anahtar Kelimeler

• Şizofreni, viral enfeksiyonlar, biyolojik belirteç

References

1. Baldi BF, Hoyer C, Novère N. Schizophrenic: forever young? Genome Med 2010; 2:32.
2. Hariri AG, Özer GU, Ceylan ME, Ceylan N, Yazan B, Önal O. Şizofreni etyolojisinde nörogelişimsel hipotez. Klinik Psikofarmakoloji Bülteni 1999; 9:99- 103.
3. Sadock BJ, Sadock VA, Ruiz P. Comprehensive Textbook of Psychiatry, 9th edition. Philadelphia, Lippincott Williams & Wilkins, 2009.
4. Pantelis C, Yucel M, Wood SJ, Velakoulis D, Sun D, Berger G et al. Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia. Schizophr Bull 2005; 31 :672-696.
5. Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull 2009; 35:528-548.
6. Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44:660-669.
7. Murray RM, Lewis SW. Is schizophrenia a neurodevelopmental disorder? BMJ (Clin Res Ed) 1987; 295:681-682.
8. Owen MJ, O'Donovan MC, Thapar A, Craddock N. Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 2011; 198:173-175.

9. Lipska BK, Weinberger DR. A neurodevelopmental model of schizophrenia: neonatal disconnection of the hippocampus. Neurotox Res. 2002; 4:469-475.
10. Van Os J, Kapur S. Schizophrenia. Lancet 2009; 374: 635-645.
11. Balım EÖ. Erken başlangıçlı şizofreni. Klinik Psikiyatri Dergisi 2001; 4:60-70.
12. Niemi LT, Suvisaari JM, Tuulio-Henriksson A, Lonnqvist JK. Childhood developmental abnormalities in schizophrenia:evidence from high-risk studies. Schizophr Res 2003; 60: 239-258.
13. Barkus E, Stirling J, Hopkins R, Lewis S. The presence of neurological soft signs along the psychosis proneness continuum. Schizophr Bull 2006; 32:573-577.
14. Brown AS, Vinogradov S, Kremen WS, Poole JH, Deicken RF, Justin D et al. Prenatal infectıon and executive dysfunction ın adult schizophrenia. Am J Psychiatry 2009; 166:683-690.
15. Keshavan MS. Development, disease and degeneration in schizophrenia: a unitary pathophysiological model. J Psychiatr Res 1999; 33:513-521.
16. Keshavan MS, Hogarty GE. Brain maturational processes and delayed onset in schizophrenia. Dev Psychopathol 1999;11:525-543.
17. Rapoport JL, Addington AM, Frangou S, Psych MR. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry. 2005; 10:434-449.
18. Lieberman AJ. Textbook of Schizophrenia. Washington DC, American Psychiatric Publishing, 2006.
19. Uhlhaas PJ, Singer W. Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 2010; 11:100-113.
20. Davies Q, Welham J, Chant D, Torrey EF, McQrath J. A systematic review and meta-analysis of northern hemisphere season of birth studies in schizophrenia. Schizophr Bull 2003; 29:587-593.
21. Brown AS, Cohen P, Greenwald S, Susser E. Nonaffective psychosis after prenatal exposure to rubella. Am J Psychiatry 2000; 157:438-443.
22. Hart DJ, Heath RG, Sautter FJ. Antiretroviral antibodies: implications for schizophrenia, schizophrenic disorders and bipolar disorder. Biol Psychiatry 1999; 45:704-714.
23. Suvisaari JM, Haukka JK, Lonnqvist JK. Season of birth among patients with schizophrenia and their siblings; evidence for the procreational habits hypothesis. Am J Psychiatry 2001; 158:519-525.
24. Harrison, G. Searching for causes of schizophrenia: The role of migrant studies. Schizophr Bull 1990; 16:663-671.
25. Goodall E. The exciting cause of certain states, at present classified under schizophrenia by psychiatrists, may be infection. J Ment Sci 1932; 78:746-755.
26. Yolken RH, Torrey EF. Viruses, schizophrenia, and bipolar disorder. Clin Microbiol Rev 1995; 8:131-145.
27. Selten JP, Frissen A, Lensvelt-Mulders G, Morgan VA Schizophrenia and 1957 pandemic of influenza: meta-analysis. Schizophr Bull 2010; 36:219-228.
28. Brüne M, Schöbel A, Karau R, Faustmann PM, Dermietzel R, Juckel G et al. Neuroanatomical correlates of suicide in psychosis: the possible role of von Economo neurons. PLoS One 2011; 6:e20936.
29. Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry 2010; 167:261–280.
30. Manjunatha N.The current swine flu pandemic may provide some opportunity for future research of schizophrenia. Indian J Med Res 2010; 132:108-109.
31. Lewis, G, David A, Andreasson S, Allebeck P. Schizophrenia and city life. Lancet 1992; 340:137-140.
32. Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 2004; 61:774-780.
33. Dora İ, Önal O, Ceylan ME, Kenar J, Kılınç E. Şizofreni ve doğum mevsimi ilişkisi. Düşünen Adam 2004;17:5-20.
34. Pan W, Xiang S, Tu H, Kastin A. Cytokines interact with the bloodbrain barrier. In Blood-Brain Barriers: From Ontogeny to Artificial Interfaces (Eds R Derietzel, , M Nedergaard):247-264. Weinheim,Wiley-VCH, 2006.
35. Herz MI, Marder SR. Schizophrenia; Comprehensive Treatment and Management. Baltimore, Lippincott Williams and Wilkins, 2002.
36. Patterson PH. Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav Brain Res 2009; 204:313-321.
37. Fatemi SH, Reutiman TJ, Folsom TD. Maternal infection leads to abnormal gene regulation and brain atrophy inmouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res 2008; 99:56-70.
38. Wintera C, Reutimanb TJ, Folsomb TD, Sohrc R, Wolfd RJ, Fatemi SH et al. Dopamine and serotonin levels following prenatal viral infection in mouse - implications for psychiatric disorders such as schizophrenia and autism. Eur Neuropsychopharmacol 2008;18:712-716.
39. Sotelo J, Corona T. Multiple varicella zoster virus and relapsing remitting multiple sclerosis. Mult Scler Int 2011; 2011:214763.
40. Boyd JH, Pulver AE, Stewart W. Season of birth: schizophrenia and bipolar disorder. Schizophr Bull 1986; 12:173-185.
41. Short SJ, Lubach GR, Karasin AI, Olsen CW, Styner M, Rebecca C et al. Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey. Biol Psychiatry 2010; 67:965-973.
42. Gotlieb- Stematsky T, Zonis J, Arlazorof A, Mozes T, Sigal M, Szekely AG. Antibodies to Epstein-Barr virus, herpes simpleks type 1, cytomegalovirus and measles virus in psychiatric patients. Arch Virol 1981; 67:333-339.
43. Torrey EF, Yolken RH, Winfrey CJ. Cytomegalovirus antibody in cerebrospinal fluid of schizophrenic patients detected by enzyme immunoassay. Science 1982; 216:892- 893.
44. Özcankaya R, Mumcu N,İstanbullu HO. Şizofrenili hastalarda herpes simpleks ve sitomegalovirus antikor düzeyleri : kontrollü bir çalışma. Klinik Psikofarmokoloji Bülteni 2000; 10:201-204.
45. Gordon YJ, Araullo-Cruz TP, Romanovski E, Ruziczka L, Balouris C, Oren J, et al. The development of on improved murine iontophoresis reactivation model for the study of H5V-1 Latency. Invest Ophthalmol Vis Sci 1986 ; 27:1230-1234.
46. Myles ME, Azcuy AM, Nguyen NT, Reisch ER, Barker SA, Thompson HW et al. Bupropion (Zyban, Wellbutrin) inhibits nicotine-induced viral reactivation in herpes simplex virus type 1 latent rabbits. J Pharmacol Exp Ther 2004; 311:640-644.
47. Solbrig MV, Koob GF, Fallon JH, Reid S, Lipkin WI. Prefrontal cortex dysfunction in Borna disease virus (BDV) infected rats. Biol Psychiatry 1996; 40: 629-636.
48. Rees S, Inder T. Fetal and neonatal origins of altered brain development. Early Hum Dev 2005; 81:753-761.
49. Bülent Demirbek, Uzm.Dr., Adana Ruh Sağlığı ve Hastalıkları Hastanesi, Adana; Osman Özdemir, Uzm.Dr.,
50. İpekyolu Develt Hastanesi, Van