The Infection Hypothesis of Schizophrenia: A Systematic Review
Alexander M. Scharko
.
DOI: 10.4236/jbbs.2011.12007   PDF    HTML     7,291 Downloads   16,945 Views   Citations

Abstract

Objectives: The objective of this paper is to accomplish a systematic review of the infection hypothesis of schizophrenia. Methods: All English language publications from January 1989 to March 2010 as related to infection and schizophrenia were obtained. Each study selected for analysis must either deal with the direct infection of an individual and schizophrenia or maternal infection during pregnancy and the subsequent development of schizophrenia in the offspring. The primary outcome measure was the calculated odds ratio and 95% confidence interval (CI). Results: Over 300 titles and abstracts were reviewed. Eight retrospective studies regarding in utero exposure were analyzed. Five nested case-controlled studies yielded an overall odds ratio of 3.58 (95% CI: 2.71 - 4.71) with a percent attributable risk of 6.3%. Three Scandinavian populational studies yielded an overall odds ratio of 0.62 (95% CI: 0.49 - 0.79). Twenty-six papers were identified as retrospective studies focused on linking evidence of past infection in individuals with history of schizophrenia. A total of 77 microorganisms were assessed with 18 (23.4%) showing a positive association with schizophrenia. But positive associations in a given trial were negative in other trials. Conclusions: Direct infection of an individual as a cause of schizophrenia is unlikely. Results were mixed regarding maternal infection, in utero exposure, and the later development of schizophrenia in the offspring and likely accounts for a modest proportion of those with schizophrenia, possibly 6%.

Share and Cite:

A. Scharko, "The Infection Hypothesis of Schizophrenia: A Systematic Review," Journal of Behavioral and Brain Science, Vol. 1 No. 2, 2011, pp. 47-56. doi: 10.4236/jbbs.2011.12007.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] R. Noll, “Infectious Insanities, Surgical Solutions: Bayard Taylor Holmes, Dementia Praecox and Laboratory Science in Early 20th-Century America. Part 1,” History of Psychiatry, Vol. 17, No. 2, 2006, pp. 183-204. doi:10.1177/0957154X06059456
[2] R. Noll, “Infec-tious Insanities, Surgical Solutions: Bayard Taylor Holmes, Dementia Praecox and Laboratory Science in Early 20th-Century America. Part 2,” History of Psychiatry, Vol. 17, No. 2, 2006, pp. 299-311. doi:10.1177/0957154X06059446
[3] D. Lewis and P. Levitt, “Schizophrenia as a disorder of neurodevelopment,” Annual Review of Neuroscience, Vol. 25, No. 2, 2002, pp. 409-432. doi:10.1146/annurev.neuro.25.112701.142754
[4] J. Rapoport, A. Addington and S. Frangou S, “The Neuro-developmental Model of Schizophrenia: Update 2005,” Molecular Psychiatry, Vol. 10, No. 5, 2005, pp. 434-449.
[5] A. Brown and E. Susser, “In Utero Infec-tion and Adult Schizophrenia,” Mental Retardation and Developmental Disabilities Research Reviews, Vol. 8, No. 1, 2002, pp. 51-57. doi:10.1002/mrdd.10004
[6] M. Debnath and T. Chaudhuri, “The Role of HLA-G in Cy-tokine Homeostasis during Early Pregnancy Complicated with Maternal Infections: A Novel Etiopathological Ap-proach to the Neurodevelopmental Understanding of Schizophrenia,” Medical Hypotheses, Vol. 66, No. 2, 2006, pp. 286-293.
[7] R. Yolken and E. Torrey, “Are Some Cases of Psychosis Caused by Microbial Agents? A Review of the Evidence,” Molecular Psychiatry, Vol. 13, No. 5, 2008, pp. 470-479.
[8] M. Egger and G. D. Smith, “Principles of and Procedures for Systematic Re-views,” In: M. Egger, G. D. Smith and D. G. Altman, Eds., Systematic Reviews in Health Care: Meta-analysis in Context, British Medical Journal, London, 2001, pp. 23-42. doi:10.1002/9780470693926.ch2
[9] K. Mullis, “The Unusual Origin of the Polymerase Chain Reaction,” Scientific American, Vol. 262, No. 4, 1990, pp. 56-65. doi:10.1038/scientificamerican0490-56
[10] B. Dawson and R. Trapp, “Basic & Clinical Biostatistics,” Lange Medical Books/McGraw-Hill, New York, 2001.
[11] C. Hennekens and S. Maynert, “Epidemiology in Medicine,” Lippincott Williams & Wilkins, Philadelphia, 1987.
[12] V. Babulas, P. Factor-Litvak, R. Goetz, C. Schaefer and A. Brown, “Prenatal Exposure to Maternal Genital and Reproductive Infections and Adult Schi-zophrenia,” American Journal of Psychiatry, Vol. 163, No. 5, 2006, pp. 927-929. doi:10.1176/appi.ajp.163.5.927
[13] A. Brown, M. Begg, S. Gravenstein, C. Schaefer, R. Wyatt, M. Bresnahan, V. Babulas and E. Susser, “Serological Evidence of Prenatal Influenza in the Etiology of Schizophrenia,” Archives of General Psychiatry, Vol. 61, No. 8, 2004, pp. 774-780. doi:10.1001/archpsyc.61.8.774
[14] A. Brown, P. Cohen, S. Greenwald and E. Susser, “Nonaffective Psychosis af-ter Prenatal Exposure to Rubella,” American Journal of Psychiatry, Vol. 157, No. 3, 2000, pp. 438-443.
[15] A. Brown, P. Cohen, J. Harkavy-Friedman, V. Babulas, D. Malaspina, J. Gorman and E. Susser, “Prenatal Rubella, Premorbid Abnormalities, and Adult Schizophrenia,” Bi-ological Psychiatry, Vol. 49, No. 6, 2001, pp. 473-486. doi:10.1016/S0006-3223(01)01068-X
[16] A. Brown, C. Schaefer, C. Quesenberry, V. Babulas and E. Susser, “Maternal Exposure to Toxoplasmosis and Risk of Schi-zophrenia in Adult Offspring,” American Journal of Psychiatry, Vol. 162, No. 4, 2005, pp. 767-773.
[17] A. Brown, C. Schaefer, C. Quesenberry, L. Shen and E. Susser, “No Evidence of Relation between Maternal Ex-posure to Herpes Simplex Virus Type 2 and Risk of Schizophrenia,” American Journal of Psychiatry, Vol. 163, No. 12, 2006, pp. 2178-2180. doi:10.1176/appi.ajp.163.12.2178
[18] A. Brown, C. Schaefer, R. Wyatt, R. Goetz, M. Begg, J. Gorman and E. Susser, “Maternal Exposure to Respiratory Infections and Adult Schizophrenia Spectrum Disorders: A Prospective Birth Cohort Study,” Schizophrenia Bulletin, Vol. 26, No. 2, 2000, pp. 287-295.
[19] S. Buka, M. Tsuang, E. Tor-rey, M. Klebanoff, D. Bernstein and R. Yolken, “Maternal Infections and Subsequent Psychosis among Offspring,” Archives of General Psychiatry, Vol. 58, No. 11, 2001, pp. 1032-1037. doi:10.1001/archpsyc.58.11.1032
[20] M. Clarke, A. Tanskanen, M. Huttunen, J. Whittaker and M. Cannon, “Evidence for an Interaction between Familial Liability and Prenatal Exposure to Infection in the Causation of Schizophrenia,” American Journal of Psychiatry, Vol. 166, No. 9, 2009, pp. 1025-1030.
[21] S. Mednick, M. Huttunen and R. Machon, “Prenatal Influenza Infections and Adult Schizophrenia,” Schizophrenia Bulletin, Vol. 20, No. 2, 1994, pp. 263-267.
[22] P. Mortensen, B. Norgaard-Pedersen, B. Waltoft, T. Sorensen, D. Hougaard, E. Torrey and R. Yolken, “Toxoplasma Gondii as a Risk Factor for Early-onset Schizophrenia: Analysis of Filter Paper Blood Samples Obtained at Birth,” Biological Psychiatry, Vol. 61, No. 5, 2007, pp. 688-693.
[23] P. Sham, C. MacClean and K. Kendler, “Risk of Schizoph-renia and Age Differences with Older Siblings,” The British Journal of Psychiatry, Vol. 163, 1993, pp. 627-633. doi:10.1192/bjp.163.5.627
[24] H. Sorensen, E. Mortensen, J. Reinisch and S. Mednick, “Association between Prenatal Exposure to Bacterial Infection and Risk of Schizophrenia,” Schizophrenia Bulletin, Vol. 35, No. 3, 2009, pp. 631-637. doi:10.1093/schbul/sbn121
[25] R. Alexander, G. Cabirac, T. Lowenkopf, M. Casanova, J. Kleinman, R. Wyatt and D. Kirch, “Search for Evidence of Herpes Simplex Virus, Type 1, or Varicella-zoster Virus Infection in Postmortem Brain Tissue from Schizophrenic Patients,” Acta Psychiatrica Scandinavica, Vol. 86, 1992, pp. 418-420.
[26] R. Alexander, S. Spector, M. Casanova, J. Kleinman, R. Wyatt and D. Kirch, “Search for Cytome-galovirus in the Postmortem Brains of Schizophrenic Pa-tients Using the Polymerase Chain Reaction,” Archives of General Psychiatry, Vol. 49, No. 1, 1992, pp. 47-53.
[27] S. Bachmann, J. Schroder, C. Bottmer, E. Torrey and R. Yolken, “Psychopathology in First-Episode Schizophrenia and Antibodies to Toxoplasma Gondii,” Psychopathology, Vol. 38, No. 2, 2005, pp. 87-90. doi:10.1159/000085349
[28] C. H. Chen, Y. L. Chiu, F. C. Wei, F. J. Koong, H. C. Liu, C. K. Shaw, H. G. Hwu and K. J. Hsiao, “High Seroprevalence of Borna Virus Infection in Schizophrenic Patients, Family Members and Mental Health Workers in Taiwan,” Molecular Psychiatry, Vol. 4, No. 1, 1999, pp. 33-38.
[29] M. Coggiano, R. Alexander, D. Kirch, R. Wyatt and H. Kulaga, “The Con-tinued Search for Evidence of Retroviral Infection in Schizophrenic Patients,” Schizophrenia Research, Vol. 5, 1991, pp. 243-247. doi:10.1016/0920-9964(91)90082-3
[30] C. Coneje-ro-Goldberg, E. Torrey and R. Yolken, “Herpesviruses and Toxoplasma Gondii in Orbital Frontal Cortex of Psychiatric Patients,” Schizophrenia Research, Vol. 60, 2003, pp. 65-69. doi:10.1016/S0920-9964(02)00160-3
[31] F. Dickerson, J. Boronow, C. Stallings, A. Origoni, I. Ruslanova and R. Yolken, “Association of Serum Antibodies to Herpes Simplex Virus 1 with Cognitive Deficits in Individuals with Schizophrenia,” Archives of General Psychiatry, Vol. 60, No. 5, 2003, pp. 466-472. doi:10.1001/archpsyc.60.5.466
[32] F. Dickerson, B. Kirkpatrick, J. Boronow, C. Stallings, A. Origoni and R. Yolken, “Deficit Schizophrenia: Association with Serum Antibodies to Cytomegalovirus,” Schizophrenia Bulletin, Vol. 32, No. 2, 2006, pp. 396-400. doi:10.1093/schbul/sbi054
[33] R. Fukuda, T. Sasaki, H. Kunugi and S. Nanko, “No Changes in Paired Viral An-tibody Titers during the Course of Acute Schizophrenia,” Neuropsychobiology, Vol. 40, No. 2, 1999, pp. 57-62.
[34] D. Hart, R. Heath, F. Sautter, B. Schwartz, R. Grarry, B. Choi, M. Beilke and L. Hart, “Antiretroviral Antibodies: Implications for Schizophrenia, Schizophrenia Spectrum Disorders, and Bipolar Disorder,” Biological Psychiatry, Vol. 45, No. 6, 1999, pp. 704-714. doi:10.1016/S0006-3223(98)00229-7
[35] K. Iwahashi, M. Watanabe, K. Nakamura, H. Suwaki, T. Nakaya, Y. Nakamura, H. Takahashi and K. Ikuta, “Clinical Investi-gation of the Relationship between Borna Disease Virus (BDV) Infection and Schizophrenia in 67 Patients in Ja-pan,” Acta Psychiatrica Scandinavica, Vol. 96, 1997, pp. 412-415. doi:10.1111/j.1600-0447.1997.tb09941.x
[36] K. Iwa-hashi, M. Watanabe, K. Nakamura, H. Suwaki, T. Nakaya, Y. Nakamura, H. Takahashi and K. Ikuta, “Borna Disease Virus Infection and Schizophrenia: Seroprevalence in Schizophrenic Patients,” Canadian Journal of Psychiatry, Vol. 43, No. 2, 1998, p. 197.
[37] K. Iwahashi, M. Watanabe, K. Nakamura, H. Suwaki, T. Nakaya, Y. Nakamura, H. Takahashi and K. Ikuta, “Borna Disease Virus Infection and Negative Syndromes in Japanese Schizophrenia Patients,” Psychiatry and Clinical Neuros-ciences, Vol. 52, No. 1, 1998, p. 119. doi:10.1111/j.1440-1819.1998.tb00984.x
[38] K. Iwa-hashi, M. Watanabe, K. Nakamura, H. Suwaki, T. Nakaya, Y. Nakamura, H. Takahashi and K. Ikuta, “Positive and Negative Syndromes, and Borna Disease Virus Infection in Schizophrenia,” Neuropsychobiology, Vol. 37, No. 2, 1998, pp. 59-64.
[39] F. Leweke, C. Gerth, D. Koethe, J. Klosterkotter, I. Ruslanova, B. Krivogorsky, E. Torrey and R. Yolken, “Antibodies to Infectious Agents in Indi-viduals with Recent Onset Schizophrenia,” European Archives of Psychiatry and Clinical Neuroscience, Vol. 254, No. 1, 2004, pp. 4-8. doi:10.1007/s00406-004-0481-6
[40] E. Lillehoj, G. Ford, S. Bachmann, J. Schroder, E. Torrey and R. Yolken, “Serum Antibodies Reactive with Non-human Primate Retroviruses Identified in Acute Onset Schizophrenia,” Journal of Neurovirology, Vol. 6, 2000, pp. 492-497. doi:10.3109/13550280009091949
[41] D. Niebuhr, A. Millikan, D. Cowan, R. Yolken, Y. Li and N. Weber, “Selected Infectious Agents and Risk of Schizophrenia among US Military Personnel,” American Journal of Psychiatry, Vol. 165, No. 1, 2008, pp. 99-106. doi:10.1176/appi.ajp.2007.06081254
[42] D. Niebuhr, A. Millikan, R. Yolken, Y. Li and N. Weber, “Results from a Hypothesis Generating Case-Controlled Study: Herpes Family Viruses and Schizophrenia among Military Per-sonnel,” Schizophrenia Bulletin, Vol. 34, No. 6, 2008, pp. 1182-1188. doi:10.1093/schbul/sbm139
[43] S. Nunes, E. Itano, M. Amarante, E. Reiche, H. Miranda, C. de Oliveira, T. Matsuo, H. Vargas and M. Watanabe, “RNA from Borna Disease Virus in Patients with Schizophrenia, Schizoaffective Patients, and in Their Biological Rela-tives,” Journal of Clinical Laboratory Analysis, Vol. 22, No. 4, 2008, pp. 314-320. doi:10.1002/jcla.20261
[44] A. Pelonero, A. Pandurangi and V. Calabrese, “Serum IgG Antibody to Herpes Viruses in Schizophrenia,” Psychiatry Research, Vol. 33, No. 1, 1990, pp. 11-17. doi:10.1016/0165-1781(90)90144-T
[45] J. Richt, R. Alexander, S. Herzog, D. Hooper, R. Kean, S. Spitsin, K. Bechter, R. Schuttler, H. Feldmann, A. Heiske, Z. Fu, B. Dietzschyold, R. Rott and H. Koprowski, “Failure to Detect Borna Disease Virus Infection in Peripheral Blood Leukocytes from Humans with Psychiatric Disorders,” Journal of Neurovirology, Vol. 3, 1997, pp. 174-178. doi:10.3109/13550289709015807
[46] A. Sier-ra-Honigmann, K. Carbone and R. Yolken, “Polymerase Chain Reaction (PCR) Search for Viral Nucleic Acid Se-quences in Schizophrenia,” British Journal of Psychiatry, Vol. 166, No. 1, 1995, pp. 55-60. doi:10.1192/bjp.166.1.55
[47] G. Tamer, D. Dundar, I. Yalug, S. Caliskan, S. Yazar and A. Aker, “The Schi-zophreina and Toxoplasma Gondii Connection: Infectious, Immune or Both?” Advances in Therapy, Vol. 25, No. 7, 2008, pp. 703-709.
[48] H. Terayama, Y. Nishino, M. Kishi, K. Ikuta, M. Itoh and K. Iwahashi, “Detection of Anti-Borna Disease Virus (BDV) Antibodies from Pa-tients with Schizophrenia and Mood Disorders in Japan,” Psychiatry Research, Vol. 120, No. 2, 2003, pp. 201-206.
[49] R. Waltrip II, R. Buchanan, A. Summerfelt, A. Breier, W. Carpenter, N. Bryant, S. Rubin and K. Carbone, “Borna Disease Virus and Schizophrenia,” Psychiatry Research, Vol. 56, No. 1, 1995, pp. 33-44. doi:10.1016/0165-1781(94)02600-N
[50] R. Yolken, S. Bachmann, I. Rouslanova, E. Lillehoj, G. Ford, E. Torrey and J. Schroeder, “Antibodies to Toxoplasma Gondii in Individuals with First-Episode Schizophrenia,” Clinical Infectious Diseases, Vol. 32, No. 5, 2001, pp. 842-844. doi:10.1086/319221
[51] C. Dalman, P. Allebeck, D. Gunnell, G. Harrison, K. Kristensson, G. Lewis, S. Lofv-ing, F. Rasmussen, S. Wicks and H. Karlsson, “Infections in the CNS during Childhood and the Risk of Subsequent Psychotic Illness: A Cohort Study of More than One Mil-lion Swedish Subjects,” American Journal of Psychiatry, Vol. 165, No. 1, 2008, pp. 59-65. doi:10.1176/appi.ajp.2007.07050740
[52] H. Koponen, P. Rantakallio, J. Veijola, P. Jones, J. Jokelainen and M. Isohanni, “Childhood Central Nervous System Infections and Risk for Schizophrenia,” European Archives of Psy-chiatry and Clinical Neurosciences, Vol. 254, 2004, pp. 9-13.
[53] S. Leask, D. Done and T. Crow, “Adult Psy-chosis, Common Childhood Infections and Neurological Soft Signs in a National Birth Cohort,” British Journal Psychiatry, Vol. 181, No. 5, 2002, pp. 387-392. doi:10.1192/bjp.181.5.387
[54] P. Rantakallio, P. Jones, J. Moring and L. von Wendt, “Association between Central Nervous System Infections during Childhood and Adult Onset Schizophrenia and Other Psychosis: A 28-Year Follow-Up,” International Journal of Epidemiology, Vol. 26, No. 4, 1997, pp. 837-843. doi:10.1093/ije/26.4.837
[55] J. Veijola, P. Jones, T. Makikyro, J. Moring, P. Rantakallio and M. Isohanni, “Early Associations of Schizophrenia in the 1966 North Finland General Population Birth Cohort,” International Journal of Mental Health, Vol. 29, 2001, pp. 84-90.
[56] E. Goodall, “The Exciting Cause of Certain States, at Present Classified under Schizophrenia by Psy-chiatrists, may be Infection,” Journal of Mental Science, Vol. 78, 1932, pp. 746-755.
[57] E. Torrey, J. Miller, R. Rawlings and R. Yolken, “Seasonality of Births in Schi-zophrenia and Bipolar Disorder: A Review of the Litera-ture,” Schizophrenia Research, Vol. 28, No. 1, 1997, pp. 1-38. doi:10.1016/S0920-9964(97)00092-3
[58] W. Adams, R. Kendell, E. Hare and P. Munk-Jorgensen, “Epidemiolog-ical Evidence that Maternal Influenza Contributes to the Aetiology of Schizophrenia,” British Journal of Psychiatry, Vol. 163, 1993, pp. 522-534. doi:10.1192/bjp.163.4.522
[59] C. Barr, S. Mednick and P. Munk-Jorgensen, “Exposure to Influenza Epidemics during Gestation and Adult Schizophrenia,” Archives of General Psychiatry, Vol. 47, No. 9, 1990, pp. 869-874.
[60] I. Jones and D. Frei, “Seasonal Births in Schizophrenia,” Acta Psychiatrica Scandinavica, Vol. 59, 1979, pp. 164-172. doi:10.1111/j.1600-0447.1979.tb06958.x
[61] R. Kendell and W. Adams, “Unexplained Fluctuations in the Risk for Schizophrenia by Month and Year of Birth,” British Journal of Psychiatry, Vol. 158, 1991, pp. 758-763.
[62] H. Kunugi, S. Nanko, N. Takei, K. Saito, N. Hayashi and H. Kazamatsuri, “Schizophrenia Follow-ing in utero Exposure to the 1957 Influenza Epidemics in Japan,” American Journal of Psychiatry, Vol. 152, No. 3, 1995, pp. 450-452.
[63] F. Limosin, F. Rouillon, C. Payan, J. M. Cohen and N. Strub, “Prenatal Exposure to Influenza as a Risk Factor for Adult Schizophrenia,” Acta Psychiatrica Scandinavica, Vol. 107, 2003, pp. 331-335. doi:10.1034/j.1600-0447.2003.00052.x
[64] J. McGrath and D. Castle, “Does Influenza Cause Schizophrenia? A Five Year Review,” Australian and New Zealand Journal of Psychiatry, Vol. 29, No. 1, 1995, pp. 23-31. doi:10.3109/00048679509075888
[65] S. Mednick, R. Machon and M. Huttunen, “An Update on the Helsinki In-fluenza Project,” Archives of General Psychiatry, Vol. 47, No. 3, 1990, p. 292.
[66] V. Morgan, D. Castle, A. Page, S. Fazio, L. Gurrin, P. Burton, P. Montgomery and A. Jablensky, “Influenza Epidemics and Incidence of Schi-zophrenia, Affective Disorders and Mental Retardation in Western Australia: No Evidence of a Major Effect,” Schizophrenia Research, Vol. 26, No. 1, 1997, pp. 25-39.
[67] E. O’Callaghan, T. Gibson, H. Colohan, D. Walshe, P. Buckley, C. Larking and J. Waddington, “Season of Birth in Schizophrenia,” British Journal of Psychiatry, Vol. 158, 1991, pp. 764-769.
[68] J. Suvi-saari, J. Haukka, A. Tanskanen, T. Hovi and J. Lonnqvist, “Association between Prenatal Exposure to Poliovirus Infection and Adult Schizophrenia,” American Journal of Psychiatry, Vol. 156, No. 7, 1999, pp. 1100-1102.
[69] N. Takei and R. Murray, “Prenatal Influenza and Schi-zophrenia,” British Journal of Psychiatry, Vol. 165, 1994, p. 833. doi:10.1192/bjp.165.6.833
[70] Y. Battle, B. Martin, J. Dorfman and L. Miller, “Seasonality and Infectious Disease in Schizophrenia: The Birth Hypothesis Revisited,” Journal of Psychiatric Practice, Vol. 33, 1999, pp. 501-509.
[71] M. Cahill, D. Chant, J. Welham and J. McGrath, “No Significance Association between Prenatal Exposure to Poliovirus and Psychosis,” Australian and New Zealand Journal of Psychiatry, Vol. 36, 2002, pp. 373-375.
[72] L. Erlenmeyer-Kimling, Z. Folnegovic, V. Hrabak-Zer- javic, B. Borcic, V. Folnegovic-Smalc and E. Susser, “Schizophrenia and Prenatal Exposure to the 1957 A2 Influenza Epidemic in Croatia,” American Journal of Psychiatry, Vol. 151, No. 10, 1994, pp. 1496-1498.
[73] J. Selten, J. Slaets and R. Kahn, “Pre-natal Exposure to Influenza and Schizophrenia in Suri-namese and Dutch Antillean Immigrants to the Nether-lands,” Schizophrenia Research, Vol. 30, No. 1, 1998, pp. 101-103. doi:10.1016/S0920-9964(97)00105-9
[74] E. Susser, S. Lin, A. Brown, L. Lumey and L. Erlenmeyer-Kimling, “No Relation between Risk of Schizophrenia and Prenatal Exposure to Influenza in Holland,” American Journal of Psychiatry, Vol. 151, No. 6, 1994, pp. 922-924.
[75] T. Westergaard, P. Mortensen, C. Pedersen, J. Wohlfahrt and M. Melbye, “Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia,” Archives of General Psychiatry, Vol. 56, No. 11, 1999, pp. 993-998. doi:10.1001/archpsyc.56.11.993
[76] A. Brown and E. Derkits, “Prenatal Infection and Schizophrenia: A Review of Epidemiologic and Translational Studies,” American Journal of Psychiatry, Vol. 167, No. 3, 2010, pp. 261-280.
[77] A. Hess, J. Buchmann, U. Zettl, S. Hen-schel, D. Schlaefke, G. Grau and R. Benecke, “Borrelia Burgdorferi Central Nervous System Infection Presenting as an Organic Schizophrenialike Disorder,” Biological Psychiatry, Vol. 45, No. 6, 1999, p. 795.
[78] M. Stoler, J. Zoldan and P. Sirota, “Schizophreniform Episode Fol-lowing Measles Infection,” British Journal of Psychiatry, Vol. 150, 1987, pp. 861-862. doi:10.1192/bjp.150.6.861
[79] A. Mitchell and D. Ma-lone, “Physical Health and Schizophrenia,” Current Opi-nion in Psychiatry, Vol. 19, No. 4, 2006, pp. 432-437.
[80] C. Carter, “Schizophrenia Susceptibility Genes Directly Implicated in the Life Cycles of Pathogens: Cytomegalovirus, Influenza, Herpes Simplex, Rubella, and Toxoplasma Gondii,” Schizophrenia Bulletin, Vol. 35, No. 6, 2009, pp. 1163-1182.
[81] D. Vercelli, “Mechanisms of the Hygiene Hypothesis - Molecular and Otherwise,” Current Opinion in Immunology, Vol. 18, 2006, pp. 733-737. doi:10.1016/j.coi.2006.09.002
[82] S. Dower, “Cytokines, Virokines and the Evolution of Immunity,” Nature Immunology, Vol. 1, No. 5, 2000, pp. 367-368.
[83] N. Nathanson and G. McFadden, “Viral Virulence,” In: N. Nathanson, Ed., Viral Pathogenesis, Lippincott-Raven, Philadelphia, 1997, pp. 85-108.
[84] J. Gilmore and L. Jarskog, “Exposure to Infection and Brain Development: Cytokines in the Pathogenesis of Schizophrenia,” Schi-zophrenia Research, Vol. 24, 1997, pp. 365-367.
[85] J. Gilmore and L. Jarskog, “Maternal Infection, Cytokines, and Risk for Schizophrenia,” In: S. Fatemi, Ed., Neurop-sychiatric Disorders and Infection, Taylor & Francis, London, 2005, pp. 96-106.
[86] S. Zammit, P. Allebeck, C. Dalman, I. Lundberg, T. Hemmingson, M. Owen and G. Lewis, “Paternal Age and Risk for Schizophrenia,” British Journal of Psychiatry, Vol. 183, No. 5, 2003, pp. 405-408. doi:10.1192/bjp.183.5.405
[87] D. Morens, G. Folkers and A. Fauci, “The Challenge of Emerging and Re-emerging Infectious Diseases,” Nature, Vol. 430, No. 6996, 2004, pp. 242-249. doi:10.1038/nature02759
[88] S. Saha, D. Chant, J. Welham and J. McGrath, “A Systematic Review of the Prevalence of Schizophrenia,” PLoS Medicine, Vol. 2, No. 5, 2005, p. e141. doi:10.1371/journal.pmed.0020141
[89] T. Y. Zhang and M. Meaney, “Epigenetics and the Environmental Regula-tion of the Genome and Its Function,” Annual Review of Psychology, Vol. 61, 2010, pp. 439-466. doi:10.1146/annurev.psych.60.110707.163625

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.