Schizophrenia, cancer and obstetric complications in an evolutionary perspective-an empirically based hypothesis

Psychiatry Investigation

Volumn 8, Issue 2, 2011, Pages 77-88

  Preti, Antonio ^a   Wilson, Daniel R ^b  

^a Centro Medico Genneruxi   (Italy)

^b CREIGHTON UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Cancer; Etiology; Evolutionary epidemiology; Immune system; Obstetric complications; Schizophrenia

Indexed keywords

ALCOHOL; APC PROTEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; DYSBINDIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GLUTAMATE RECEPTOR 3; MICRORNA; NEU DIFFERENTIATION FACTOR; NEUROLEPTIC AGENT; NEUROTENSIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ALCOHOL CONSUMPTION; APOPTOSIS; BLADDER CANCER; CANCER INCIDENCE; CANCER INVASION; CANCER RISK; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; COLORECTAL CANCER; DIET; FITNESS; GENE; GENE EXPRESSION; GENE MUTATION; GENETIC ASSOCIATION; HEREDITY; HERITABILITY; HUMAN; HYPERPROLACTINEMIA; HYPOTHESIS; IMMUNOSURVEILLANCE; INFLAMMATION; LUNG CANCER; MEDLINE; MELANOMA; META ANALYSIS; METABOLIC SYNDROME X; MORBIDITY; MORTALITY; NEOPLASM; NERVE CELL DIFFERENTIATION; NONHUMAN; OBESITY; PHARMACOGENETICS; PREGNANCY COMPLICATION; PREVALENCE; PROSTATE CANCER; PSYCHOSIS; REVIEW; RISK REDUCTION; SCHIZOPHRENIA; SIBLING; SIGNAL TRANSDUCTION; SMOKING; SURVIVAL RATE; SYSTEMATIC REVIEW; TREATMENT REFUSAL;

EID: 79960953592     PISSN: 17383684     EISSN: None     Source Type: Journal    
DOI: 10.4306/pi.2011.8.2.77     Document Type: Review

References (206)

1. Joo EJ, Lee KY, Jeong SH, Roh MS, Kim SH, Ahn YM, et al. AKT1 gene polymorphisms and obstetric complications in the patients with schizophrenia. Psychiatry Investig 2009;6:102-107.
2. Kalkman HO. The role of the phosphatidylinositide 3-kinase-protein kinase B pathway in schizophrenia. Pharmacol Ther 2006;110:117-134.
3. Preti A. Reduced risk of cancer in schizophrenia: a role for obstetric complications? Acta Psychiatr Scand 2008;118:251-253; author reply 253.
4. Sacker A, Done DJ, Crow TJ, Golding J. Antecedents of schizophrenia and affective illness. Obstetric complications. Br J Psychiatry 1995; 166:734-741.
5. Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: historical and meta-analytic review. Am J Psychiatry 2002;159:1080-1092.
6. Lichtermann D, Ekelund J, Pukkala E, Tanskanen A, LÖnnqvist J. Incidence of cancer among persons with schizophrenia and their relatives. Arch Gen Psychiatry 2001;58:573-578.
7. Catts VS, Catts SV, O'Toole BI, Frost AD. Cancer incidence in patients with schizophrenia and their first-degree relatives-a meta-analysis. Acta Psychiatr Scand 2008;117:323-336.
8. Wilson DR, Cory AG. The Evolutionary Epidemiology of Mania & Depression. New York, NY: Mellen Press; 2008.
9. Stevens A, Price J. Evolutionary psychiatry. A New Beginning. London and New York: Routledge; 1996.
10. Wilson DR. Evolutionary epidemiology. Acta Biotheor 1992;40:87-89.
11. Harrison G, Hopper K, Craig T, Laska E, Siegel C, Wanderling J, et al. Recovery from psychotic illness: a 15- and 25-year international follow- up study. Br J Psychiatry 2001;178:506-517.
12. Leucht S, Burkard T, Henderson J, Maj M, Sartorius N. Physical illness and schizophrenia: a review of the literature. Acta Psychiatr Scand 2007; 116:317-333.
13. Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 2007;64:1123-1131.
14. Lauber C, Keller C, Eichenberger A, RÖssler W. Family burden during exacerbation of schizophrenia: quantification and determinants of additional costs. Int J Soc Psychiatry 2005;51:259-264.
15. Knapp M, Mangalore R, Simon J. The global costs of schizophrenia. Schizophr Bull 2004;30:279-293.
16. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev 2008;30: 67-76.
17. Sullivan, PF. The genetics of schizophrenia. PLoS Med 2005;2:e212.
18. Tienari P, Wynne LC, Sorri A, Lahti I, Läksy K, Moring J, et al. Genotype- environment interaction in schizophrenia-spectrum disorder. Longterm follow-up study of Finnish adoptees. Br J Psychiatry 2004;184:216-222.
19. Cannon TD, Kaprio J, LÖnnqvist J, Huttunen M, Koskenvuo M. The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. Arch Gen Psychiatry 1998;55:67-74.
20. Cardno AG, Gottesman II. Twin studies of schizophrenia: from bowand- arrow concordances to star wars Mx and functional genomics. Am J Med Genet 2000;97:12-17.
21. Gottesman II, Erlenmeyer-Kimling L. Family and twin strategies as a head start in defining prodromes and endophenotypes for hypothetical early-interventions in schizophrenia. Schizophr Res 2001;51:93-102.
22. Kendler KS, McGuire M, Gruenberg AM, O'Hare A, Spellman M, Walsh D. The Roscommon Family Study. I. Methods, diagnosis of probands, and risk of schizophrenia in relatives. Arch Gen Psychiatry 1993; 50:527-540.
23. Mortensen PB, Pedersen CB, Westergaard T, Wohlfahrt J, Ewald H, Mors O, 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.
24. Tienari P, Wynne LC, Läksy K, Moring J, Nieminen P, Sorri A, et al. Genetic boundaries of the schizophrenia spectrum: evidence from the Finnish Adoptive Family Study of Schizophrenia. Am J Psychiatry 2003; 160:1587-1594.
25. Keshavan MS, Tandon R, Boutros NN, Nasrallah HA. Schizophrenia, "just the facts": what we know in 2008 Part 3: neurobiology. Schizophr Res 2008;106:89-107.
26. Boyle M. Schizophrenia: A Scientific Delusion? 2 edition (first published in 1990). New York: Routledge; 2002.
27. Craddock N, Owen MJ. The beginning of the end for the Kraepelinian dichotomy. Br J Psychiatry 2005;186:364-366.
28. Peralta V, Cuesta MJ. A dimensional and categorical architecture for the classification of psychotic disorders. World Psychiatry 2007;6:100-101.
29. Crow TJ. Craddock & Owen vs Kraepelin: 85 years late, mesmerised by "polygenes". Schizophr Res 2008;103:156-160.
30. Jablensky A. Subtyping schizophrenia: implications for genetic research. Mol Psychiatry 2006;11:815-836.
31. Hiroeh U, Kapur N, Webb R, Dunn G, Mortensen PB, Appleby L. Deaths from natural causes in people with mental illness: a cohort study. J Psychosom Res 2008;64:275-283.
32. Harris EC, Barraclough B. Excess mortality of mental disorder. Br J Psychiatry 1998;173:11-53.
33. Palmer BA, Pankratz VS, Bostwick JM. The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry 2005;62:247-253.
34. Cividini A, Pistorio A, Regazzetti A, Cerino A, Tinelli C, Mancuso A, et al. Hepatitis C virus infection among institutionalised psychiatric patients: a regression analysis of indicators of risk. J Hepatol 1997;27:455-463.
35. Ohta Y, Nakane Y, Mine M, Nakama I, Michitsuji S, Araki K, et al. The epidemiological study of physical morbidity in schizophrenics--2. Association between schizophrenia and incidence of tuberculosis. Jpn J Psychiatry Neurol 1988;42:41-47.
36. Wainberg ML, Cournos F, McKinnon K, Berkman A. HIV and hepatitis C in patients with schizophrenia. In: Meyer JM, Nasrallah HA, eds. Medical illness and schizophrenia. Washington, DC: American Psychiatric Publishing Inc, 2003, p.115-140.
37. Filik R, Sipos A, Kehoe PG, Burns T, Cooper SJ, Stevens H, et al. The cardiovascular and respiratory health of people with schizophrenia. Acta Psychiatr Scand 2006;113:298-305.
38. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999;156:1686-1696.
39. Heiskanen T, Niskanen L, Lyytikäinen R, Saarinen PI, Hintikka J. Metabolic syndrome in patients with schizophrenia. J Clin Psychiatry 2003; 64:575-579.
40. Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, et al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry 2002;59:337-345.
41. Goff DC, Sullivan LM, McEvoy JP, Meyer JM, Nasrallah HA, Daumit GL, et al. A comparison of ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls. Schizophr Res 2005;80:45-53.
42. McDermott S, Moran R, Platt T, Isaac T, Wood H, Dasari S. Heart disease, schizophrenia, and affective psychoses: epidemiology of risk in primary care. Community Ment Health J 2005;41:747-755.
43. Friedlander AH, Marder SR. The psychopathology, medical management and dental implications of schizophrenia. J Am Dent Assoc 2002; 133:603-610; quiz 624-625.
44. McCreadie RG, Stevens H, Henderson J, Hall D, McCaul R, Filik R, et al. The dental health of people with schizophrenia. Acta Psychiatr Scand 2004;110:306-310.
45. McCreadie RG; Scottish Schizophrenia Lifestyle Group. Diet, smoking and cardiovascular risk in people with schizophrenia: descriptive study. Br J Psychiatry 2003;183:534-539.
46. Nosé M, Barbui C, Tansella M. How often do patients with psychosis fail to adhere to treatment programmes? A systematic review. Psychol Med 2003;33:1149-1160.
47. Newcomer JW. Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry 2007;68 Suppl 4:8-13.
48. Østbye T, Curtis LH, Masselink LE, Hutchison S, Wright A, Dans PE, et al. Atypical antipsychotic drugs and diabetes mellitus in a large outpatient population: a retrospective cohort study. Pharmacoepidemiol Drug Saf 2005;14:407-415.
49. Fontaine KR, Heo M, Harrigan EP, Shear CL, Lakshminarayanan M, Casey DE, et al. Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate. Psychiatry Res 2001;101:277-288.
50. Barak Y, Achiron A, Mandel M, Mirecki I, Aizenberg D. Reduced cancer incidence among patients with schizophrenia. Cancer 2005;104: 2817-2821.
51. Cohen M, Dembling B, Schorling J. The association between schizophrenia and cancer: a population-based mortality study. Schizophr Res 2002; 57:139-146.
52. Dalton SO, Mellemkjaer L, Thomassen L, Mortensen PB, Johansen C. Risk for cancer in a cohort of patients hospitalized for schizophrenia in Denmark, 1969-1993. Schizophr Res 2005;75:315-324.
53. Grinshpoon A, Barchana M, Ponizovsky A, Lipshitz I, Nahon D, Tal O, et al. Cancer in schizophrenia: is the risk higher or lower? Schizophr Res 2005;73:333-341.
54. Hamilton WD. The evolution of altruistic behaviour. Am Nat 1963;97: 354-356.
55. Hamilton WD. The genetical evolution of social behaviour. J Theor Biol 1964;7:1-52.
56. Lane A, Byrne M, Mulvany F, Kinsella A, Waddington JL, Walsh D, et al. Reproductive behaviour in schizophrenia relative to other mental disorders: evidence for increased fertility in men despite decreased marital rate. Acta Psychiatr Scand 1995;91:222-228.
57. Srinivasan TN, Padmavati R. Fertility and schizophrenia: evidence for increased fertility in the relatives of schizophrenic patients. Acta Psychiatr Scand 1997;96:260-264.
58. Erlenmeyer-Kimling L, Nicol S, Rainer JD, Deming E. Changes in fertility rates of schizophrenic patients in New York. Am J Psychiatry 1969; 125:916-927.
59. Howard LM, Kumar C, Leese M, Thornicroft G. The general fertility rate in women with psychotic disorders. Am J Psychiatry 2002;159: 991-997.
60. Sullivan RJ, Allen JS. Natural selection and schizophrenia. Behav Brain Sci 2004;27:865-866.
61. Haukka J, Suvisaari J, LÖnnqvist J. Fertility of patients with schizophrenia, their siblings, and the general population: a cohort study from 1950 to 1959 in Finland. Am J Psychiatry 2003;160:460-463.
62. Svensson AC, Lichtenstein P, Sandin S, Hultman CM. Fertility of firstdegree relatives of patients with schizophrenia: a three generation perspective. Schizophr Res 2007;91:238-245.
63. de Girolamo G, Bassi M, Neri G, Ruggeri M, Santone G, Picardi A. The current state of mental health care in Italy: problems, perspectives, and lessons to learn. Eur Arch Psychiatry Clin Neurosci 2007;257:83-91.
64. Huxley J, Mayr E, Osmond H, Hoffer A. Schizophrenia as a genetic morphism. Nature 1964;204:220-221.
65. Odegaard F. Mortality in Norwegian mental hospitals from 1916 to 1933. Acta Psychiatr Scand 1936;11:323-356.
66. Commissioners in Lunacy for England and Wales. Annual Report. London: HMSO; 1909.
67. Jablensky A, Lawrence D. Schizophrenia and cancer: is there a need to invoke a protective gene? Arch Gen Psychiatry 2001;58:579-580.
68. Gulbinat W, Dupont A, Jablensky A, Jensen OM, Marsella A, Nakane Y, et al. Cancer incidence of schizophrenic patients. Results of record linkage studies in three countries. Br J Psychiatry Suppl 1992;18:75-83.
69. de Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res 2005;76:135-157.
70. Lohr JB, Flynn K. Smoking and schizophrenia. Schizophr Res 1992;8:93-102.
71. Harris JE, Thun MJ, Mondul AM, Calle EE. Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8. BMJ 2004;328:72.
72. Brown S, Birtwistle J, Roe L, Thompson C. The unhealthy lifestyle of people with schizophrenia. Psychol Med 1999;29:697-701.
73. Cargiulo T. Understanding the health impact of alcohol dependence. Am J Health Syst Pharm 2007;64:S5-S11.
74. Cradock-O'Leary J, Young AS, Yano EM, Wang M, Lee ML. Use of general medical services by VA patients with psychiatric disorders. Psychiatr Serv 2002;53:874-878.
75. Band PR, Le ND, Fang R, Deschamps M, Gallagher RP, Yang P. Identification of occupational cancer risks in British Columbia. A population- based case-control study of 995 incident breast cancer cases by menopausal status, controlling for confounding factors. J Occup Environ Med 2000;42:284-310.
76. Band PR, Le ND, MacArthur AC, Fang R, Gallagher RP. Identification of occupational cancer risks in British Columbia: a population-based case-control study of 1129 cases of bladder cancer. J Occup Environ Med 2005;47:854-858.
77. Csatary LK. Chlorpromazines and cancer. Lancet 1972;2:338-339.
78. Driscoll JS, Melnick NR, Quinn FR, Lomax N, Davignon JP, Ing R, et al. Psychotropic drugs as potential antitumor agents: a selective screening study. Cancer Treat Rep 1978;62:45-74.
79. Dalton SO, Johansen C, Poulsen AH, Nørgaard M, Sørensen HT, McLaughlin JK, et al. Cancer risk among users of neuroleptic medication: a population-based cohort study. Br J Cancer 2006;95:934-939.
80. Mothlagh PB, Henriksson R, Grankvist K. Chlorpromazine enhancement of epirubicin cytotoxicity in vitro: effects on plasma membrane and DNA damage. Drug Metabol Drug Interact 1992;10:169-176.
81. Torrey EF. Prostate cancer and schizophrenia. Urology 2006;68:1280-1283.
82. Steiner MS, Raghow S, Neubauer BL. Selective estrogen receptor modulators for the chemoprevention of prostate cancer. Urology 2001;57:68-72.
83. Mortimer AM. Relationship between estrogen and schizophrenia. Expert Rev Neurother 2007;7:45-55.
84. Halbreich U, Kinon BJ, Gilmore JA, Kahn LS. Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects. Psychoneuroendocrinology 2003;28:53-67.
85. Jeste DV, Gladsjo JA, Lindamer LA, Lacro JP. Medical comorbidity in schizophrenia. Schizophr Bull 1996;22:413-430.
86. Levav I, Lipshitz I, Novikov I, Pugachova I, Kohn R, Barchana M, et al. Cancer risk among parents and siblings of patients with schizophrenia. Br J Psychiatry 2007;190:156-161.
87. Dalton SO, Laursen TM, Mellemkjaer L, Johansen C, Mortensen PB. Risk for cancer in parents of patients with schizophrenia. Am J Psychiatry 2004;161:903-908.
88. Dong C, Hemminki K. Modification of cancer risks in offspring by sibling and parental cancers from 2,112,616 nuclear families. Int J Cancer 2001;92:144-150.
89. Imsland AK, Eldon BJ, Arinbjarnarson S, Egilsson V, Tulinius H, TryggvadÓttir L, et al. Genetic epidemiologic aspects of gastric cancer in Iceland. J Am Coll Surg 2002;195:181-186; discussion 186-187.
90. Matikaine MP, Pukkala E, Schleutker J, Tammela TL, Koivisto P, Sankila R, et al. Relatives of prostate cancer patients have an increased risk of prostate and stomach cancers: a population-based, cancer registry study in Finland. Cancer Causes Control 2001;12:223-230.
91. Kerber RA, O'Brien E. A cohort study of cancer risk in relation to family histories of cancer in the Utah population database. Cancer 2005; 103:1906-1915.
92. Li X, Hemminki K. Inherited predisposition to early onset lung cancer according to histological type. Int J Cancer 2004;112:451-457.
93. Lynch HT, de la Chapelle A. Genetic susceptibility to non-polyposis colorectal cancer. J Med Genet 1999;36:801-818.
94. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003;348:919-932.
95. Lewis DA, Levitt P. Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 2002;25:409-432.
96. Portin P, Alanen YO. A critical review of genetic studies of schizophrenia. I. Epidemiological and brain studies. Acta Psychiatr Scand 1997; 95:1-5.
97. Abel KM, Allin MP, Jirtle RL. Schizophrenia, cancer and imprinting: early nutritional influences. Br J Psychiatry 2006;188:394.
98. Tsankova N, Renthal W, Kumar A, Nestler EJ. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 2007;8:355-367.
99. Owen MJ, Craddock N, O'Donovan MC. Schizophrenia: genes at last? Trends Genet 2005;21:518-525.
100. DeLisi L, Shaw SH, Crow TJ, Shields G, Smith AB, Larach VW, et al. A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizophrenia or schizoaffective disorder. Am J Psychiatry 2002;159:803-812.
101. Maier W, Zobel A, Kühn KU. Clinical impact of recently detected susceptibility genes for schizophrenia. Dialogues Clin Neurosci 2006;8: 79-84.
102. Foster HD, Hoffer A. Schizophrenia and cancer: the adrenochrome balanced morphism. Med Hypotheses 2004;62:415-419.
103. Keller MC, Miller G. Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best? Behav Brain Sci 2006;29:385-404; discussion 405-452.
104. Mittal VA, Ellman LM, Cannon TD. Gene-environment interaction and covariation in schizophrenia: the role of obstetric complications. Schizophr Bull 2008;34:1083-1094.
105. Preti A, Miotto P. Genetics, perinatal insult, and schizophrenia: the mechanism underlying an increased prevalence of perinatal complications among individuals with a diagnosis of schizophrenia? Curr Psychiatry Rev 2005;1:139-150.
106. Boksa P, El-Khodor BF. Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders. Neurosci Biobehav Rev 2003;27: 91-101.
107. Engel SA, Erichsen HC, Savitz DA, Thorp J, Chanock SJ, Olshan AF. Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms. Epidemiology 2005;16:469-477.
108. Fatemi SH, Emamian ES, Kist D, Sidwell RW, Nakajima K, Akhter P, et al. Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. Mol Psychiatry 1999;4:145-154.
109. Geddes JR, Verdoux H, Takei N, Lawrie SM, Bovet P, Eagles JM, et al. Schizophrenia and complications of pregnancy and labor: an individual patient data meta-analysis. Schizophr Bull 1999;25:413-423.
110. Kipnis J, Yoles E, Schori H, Hauben E, Shaked I, Schwartz M. Neuronal survival after CNS insult is determined by a genetically encoded autoimmune response. J Neurosci 2001;21:4564-4571.
111. Friedman EA, Neff RK. Labor and Delivery Impact on Offspring. Littleton, MA: PSG Publication; 1987.
112. Paneth N, Stark RI. Cerebral palsy and mental retardation in relation to indicators of perinatal asphyxia. An epidemiologic overview. Am J Obstet Gynecol 1983;147:960-966.
113. Clarke MC, Harley M, Cannon M. The role of obstetric events in schizophrenia. Schizophr Bull 2006;32:3-8.
114. Isohanni M, Miettunen J, Mäki P, Murray GK, Ridler K, Lauronen E, et al. Risk factors for schizophrenia. Follow-up data from the Northern Finland 1966 Birth Cohort Study. World Psychiatry 2006;5:168-171.
115. Hollister JM, Laing P, Mednick SA. Rhesus incompatibility as a risk factor for schizophrenia in male adults. Arch Gen Psychiatry 1996;53: 19-24.
116. Palmer CG, Turunen JA, Sinsheimer JS, Minassian S, Paunio T, LÖnnqvist J, et al. RHD maternal-fetal genotype incompatibility increases schizophrenia susceptibility. Am J Hum Genet 2002;71:1312-1319.
117. Walshe M, McDonald C, Taylor M, Zhao J, Sham P, Grech A, et al. Obstetric complications in patients with schizophrenia and their unaffected siblings. Eur Psychiatry 2005;20:28-34.
118. Preti A, Cardascia L, Zen T, Marchetti M, Favaretto G, Miotto P. Risk for obstetric complications and schizophrenia. Psychiatry Res 2000;96: 127-139.
119. Ohara K, Tanabu S, Yoshida K, Sato Y, Shibuya H. Obstetric complications in siblings of Japanese schizophrenics: data from the Maternal and Child Health Handbook. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:617-620.
120. Preti A, Miotto P, Zen T. Perinatal complications, genetic risk and schizophrenia. Acta Psychiatr Scand 1998;97:381-383.
121. McNeil TF, Cantor-Graae E, Torrey EF, Sjöström K, Bowler A, Taylor E, et al. Obstetric complications in histories of monozygotic twins discordant and concordant for schizophrenia. Acta Psychiatr Scand 1994;89: 196-204.
122. Feinberg I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res 1982;17:319-334.
123. Walker E, Bollini AM. Pubertal neurodevelopment and the emergence of psychotic symptoms. Schizophr Res 2002;54:17-23.
124. Catts VS, Catts SV. Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene? Schizophr Res 2000; 41:405-415.
125. Park JK, Lee HJ, Kim JW, Park YH, Lee SS, Chang HI, et al. Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients. Schizophr Res 2004;67:71-74.
126. Cui DH, Jiang KD, Jiang SD, Xu YF, Yao H. The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia. Mol Psychiatry 2005;10:669-677.
127. Morelli C, Karayianni E, Magnanini C, Mungall AJ, Thorland E, Negrini M, et al. Cloning and characterization of the common fragile site FRA6F harboring a replicative senescence gene and frequently deleted in human tumors. Oncogene 2002;21:7266-7276.
128. Britsch S. The neuregulin-I/ErbB signaling system in development and disease. Adv Anat Embryol Cell Biol 2007;190:1-65.
129. Falls DL. Neuregulins: functions, forms, and signaling strategies. Exp Cell Res 2003;284:14-30.
130. Bjarnadottir M, Misner DL, Haverfield-Gross S, Bruun S, Helgason VG, Stefansson H, et al. Neuregulin1 (NRG1) signaling through Fyn modulates NMDA receptor phosphorylation: differential synaptic function in NRG1+/- knock-outs compared with wild-type mice. J Neurosci 2007; 27:4519-4529.
131. Roesler R, Henriques JA, Schwartsmann G. Gastrin-releasing peptide receptor as a molecular target for psychiatric and neurological disorders. CNS Neurol Disord Drug Targets 2006;5:197-204.
132. Olincy A, Leonard S, Young DA, Sullivan B, Freedman R. Decreased bombesin peptide response to cigarette smoking in schizophrenia. Neuropsychopharmacology 1999;20:52-59.
133. Kinkead B, Nemeroff CB. Neurotensin, schizophrenia, and antipsychotic drug action. Int Rev Neurobiol 2004;59:327-349.
134. Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA, et al. microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 2007;8: R27.
135. Riley DE, Krieger JN. Short tandem repeat (STR) replacements in UTRs and introns suggest an important role for certain STRs in gene expression and disease. Gene 2005;344:203-211.
136. Juvonen H, Reunanen A, Haukka J, Muhonen M, Suvisaari J, Arajärvi R, et al. Incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes mellitus. Arch Gen Psychiatry 2007;64:894-899.
137. Mors O, Mortensen PB, Ewald H. A population-based register study of the association between schizophrenia and rheumatoid arthritis. Schizophr Res 1999;40:67-74.
138. Torrey EF, Yolken RH. The schizophrenia-rheumatoid arthritis connection: infectious, immune, or both? Brain Behav Immun 2001;15:401-410.
139. Klimkeit EI, Bradshaw JL. Anomalous lateralisation in neurodevelopmental disorders. Cortex 2006;42:113-116.
140. Preti A, Sardu C, Piga A. Mixed-handedness is associated with the reporting of psychotic-like beliefs in a non-clinical Italian sample. Schizophr Res 2007;92:15-23.
141. Preti A, Lai A, Serra M, Zurrida GG. Mixed handedness prevails among children and adolescents with infantile asthma and diabetes. Pediatr Allergy Immunol 2008;19:769-772.
142. Strous RD, Shoenfeld Y. Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. J Autoimmun 2006;27:71-80.
143. Yovel G, Sirota P, Mazeh D, Shakhar G, Rosenne E, Ben-Eliyahu S. Higher natural killer cell activity in schizophrenic patients: the impact of serum factors, medication, and smoking. Brain Behav Immun 2000;14:153-169.
144. Peebles KA, Lee JM, Mao JT, Hazra S, Reckamp KL, Krysan K, et al. Inflammation and lung carcinogenesis: applying findings in prevention and treatment. Expert Rev Anticancer Ther 2007;7:1405-1421.
145. Rasmussen HB, Timm S, Wang AG, Søeby K, Lublin H, Fenger M, et al. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia. Am J Psychiatry 2006;163:507-511.
146. St-Gelais F, Jomphe C, Trudeau LE. The role of neurotensin in central nervous system pathophysiology: what is the evidence? J Psychiatry Neurosci 2006;31:229-245.
147. Geroldi D, Emanuele E, Martinelli V, Pesenti S. Schizophrenia and cancer risk: can the CCR5-delta 32 chemokine receptor gene mutation play a role? Med Hypotheses 2006;67:427-428.
148. Lasky JL, Wu H. Notch signaling, brain development, and human disease. Pediatr Res 2005;57:104R-109R.
149. Teunis MA, Kavelaars A, Voest E, Bakker JM, Ellenbroek BA, Cools AR, et al. Reduced tumor growth, experimental metastasis formation, and angiogenesis in rats with a hyperreactive dopaminergic system. FASEB J 2002;16:1465-1457.
150. Hashimoto K, Ishiwata K. Sigma receptor ligands: possible application as therapeutic drugs and as radiopharmaceuticals. Curr Pharm Des 2006; 12:3857-3876.
151. Nicodemus KK, Marenco S, Batten AJ, Vakkalanka R, Egan MF, Straub RE, et al. Serious obstetric complications interact with hypoxia-regulated/ vascular-expression genes to influence schizophrenia risk. Mol Psychiatry 2008;13:873-877.
152. Schmidt-Kastner R, van Os J, W M Steinbusch H, Schmitz C. Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia. Schizophr Res 2006;84:253-271.
153. Williams GC. Pleiotropy, natural selection, and the evolution of senescence. Evolution 1957;11:398-411.
154. Crespi B, Summers K, Dorus S. Adaptive evolution of genes underlying schizophrenia. Proc Biol Sci 2007;274:2801-2810.
155. Shi J, Gershon ES, Liu C. Genetic associations with schizophrenia: meta- analyses of 12 candidate genes. Schizophr Res 2008;104:96-107.
156. Jones RE, Lopez KH. Human Reproductive Biology. Burlington, MA: Academic Press; 2006.
157. Crow TJ. The 'big bang' theory of the origin of psychosis and the faculty of language. Schizophr Res 2008;102:31-52.
158. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, et al. Psychological functioning and health-related quality of life in adulthood after preterm birth. Dev Med Child Neurol 2007;49:597-602.
159. Obel C, Hedegaard M, Henriksen TB, Secher NJ, Olsen J. Psychological factors in pregnancy and mixed-handedness in the offspring. Dev Med Child Neurol 2003;45:557-561.
160. O'Callaghan MJ, Burn YR, Mohay HA, Rogers Y, Tudehope DI. The prevalence and origins of left hand preference in high risk infants, and its implications for intellectual, motor and behavioural performance at four and six years. Cortex 1993;29:617-627.
161. Dragovic M, Hammond G. Handedness in schizophrenia: a quantitative review of evidence. Acta Psychiatr Scand 2005;111:410-419.
162. Sommer I, Ramsey N, Kahn R, Aleman A, Bouma A. Handedness, language lateralisation and anatomical asymmetry in schizophrenia: meta-analysis. Br J Psychiatry 2001;178:344-351.
163. Panksepp J, Panksepp JB. The seven sins of evolutionary psychology. Evolution Cognition 2000;6:108-131.
164. Burdick KE, DeRosse P, Kane JM, Lencz T, Malhotra AK. Association of genetic variation in the MET proto-oncogene with schizophrenia and general cognitive ability. Am J Psychiatry 2010;167:436-443.
165. Rybakowski JK. Matrix metalloproteinase-9 (MMP9)-a mediating enzyme in cardiovascular disease, cancer, and neuropsychiatric disorders. Cardiovasc Psychiatry Neurol 2009;2009:904836.
166. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 2008;320: 539-543.
167. Sun J, Jia P, Fanous AH, van den Oord E, Chen X, Riley BP, et al. Schizophrenia gene networks and pathways and their applications for novel candidate gene selection. PLoS One 2010;5:e11351.
168. Lewis G, David A, Andréasson S, Allebeck P. Schizophrenia and city life. Lancet 1992;340:137-140.
169. Pedersen CB, Mortensen PB. Evidence of a dose-response relationship between urbanicity during upbringing and schizophrenia risk. Arch Gen Psychiatry 2001;58:1039-1046.
170. Kirkbride JB, Fearon P, Morgan C, Dazzan P, Morgan K, Tarrant J, et al. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study. Arch Gen Psychiatry 2006;63:250-258.
171. Boydell J, van Os J, McKenzie K, Allardyce J, Goel R, McCreadie RG, et al. Incidence of schizophrenia in ethnic minorities in London: ecological study into interactions with environment. BMJ 2001;323:1336-1338.
172. Cantor-Graae E, Selten JP. Schizophrenia and migration: a meta-analysis and review. Am J Psychiatry 2005;162:12-24.
173. Fearon P, Kirkbride JB, Morgan C, Dazzan P, Morgan K, Lloyd T, et al. Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP study. Incidence of Psychol Med 2006;36:1541-1550.
174. McGrath JJ, Welham JL. Season of birth and schizophrenia: a systematic review and meta-analysis of data from the Southern Hemisphere. Schizophr Res 1999;35:237-242.
175. Davies G, Welham J, Chant D, Torrey EF, McGrath J. A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophr Bull 2003;29:587-593.
176. Mednick SA, Machon RA, Huttunen MO, Bonett D. Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 1988;45:189-192.
177. Bagalkote H, Pang D, Jones P. Maternal influenza and schizophrenia in the offspring. Int J Ment Health 2001;29:3-21.
178. Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 2004;61:774-780.
179. Brown AS, Cohen P, Greenwald S, Susser E. Nonaffective psychosis after prenatal exposure to rubella. Am J Psychiatry 2000;157:438-443.
180. Suvisaari J, Haukka J, Tanskanen A, Hovi T, Lönnqvist J. Association between prenatal exposure to poliovirus infection and adult schizophrenia. Am J Psychiatry 1999;156:1100-1102.
181. Brown AS, Schaefer CA, Quesenberry CP Jr, Liu L, Babulas VP, Susser ES. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Am J Psychiatry 2005;162:767-773.
182. Torrey EF, Bartko JJ, Lun ZR, Yolken RH. Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull 2007;33:729-736.
183. Koponen H, Rantakallio P, Veijola J, Jones P, Jokelainen J, Isohanni M. Childhood central nervous system infections and risk for schizophrenia. Eur Arch Psychiatry Clin Neurosci 2004;254:9-13.
184. Dalman C, Allebeck P, Gunnell D, Harrison G, Kristensson K, Lewis G, et al. Infections in the CNS during childhood and the risk of subsequent psychotic illness: a cohort study of more than one million Swedish subjects. Am J Psychiatry 2008;165:59-65.
185. Susser ES, Lin SP. Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944-1945. Arch Gen Psychiatry 1992;49:983-988.
186. St Clair D, Xu M, Wang P, Yu Y, Fang Y, Zhang F, et al. Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959-1961. JAMA 2005;294:557-562.
187. Brown AS, Susser ES. Prenatal nutritional deficiency and risk of adult schizophrenia. Schizophr Bull 2008;34:1054-1063.
188. Selten JP, van der Graaf Y, van Duursen R, Gispen-de Wied CC, Kahn RS. Psychotic illness after prenatal exposure to the 1953 Dutch Flood Disaster. Schizophr Res 1999;35:243-245.
189. Mäki P, Veijola J, Rantakallio P, Jokelainen J, Jones PB, Isohanni M. Schizophrenia in the offspring of antenatally depressed mothers: a 31-year follow- up of the Northern Finland 1966 Birth Cohort. Schizophr Res 2004; 66:79-81.
190. Myhrman A, Rantakallio P, Isohanni M, Jones P, Partanen U. Unwantedness of a pregnancy and schizophrenia in the child. Br J Psychiatry 1996;169:637-640.
191. van Os J, Selten JP. Prenatal exposure to maternal stress and subsequent schizophrenia. The May 1940 invasion of The Netherlands. Br J Psychiatry 1998;172:324-326.
192. Beydoun H, Saftlas AF. Physical and mental health outcomes of prenatal maternal stress in human and animal studies: a review of recent evidence. Paediatr Perinat Epidemiol 2008;22:438-466.
193. Rosso IM, Cannon TD, Huttunen T, Huttunen MO, Lönnqvist J, Gasperoni TL. Obstetric risk factors for early-onset schizophrenia in a Finnish birth cohort. Am J Psychiatry 2000;157:801-807.
194. Zornberg GL, Buka SL, Tsuang MT. Hypoxic-ischemia-related fetal/ neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study. Am J Psychiatry 2000;157: 196-202.
195. Rifkin L, Lewis S, Jones P, Toone B, Murray R. Low birth weight and schizophrenia. Br J Psychiatry 1994;165:357-362.
196. Dalman C, Thomas HV, David AS, Gentz J, Lewis G, Allebeck P. Signs of asphyxia at birth and risk of schizophrenia. Population-based casecontrol study. Br J Psychiatry 2001;179:403-408.
197. Wahlbeck K, Forsén T, Osmond C, Barker DJ, Eriksson JG. Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood. Arch Gen Psychiatry 2001; 58:48-52.
198. Buka SL, Tsuang MT, Lipsitt LP. Pregnancy/delivery complications and psychiatric diagnosis. A prospective study. Arch Gen Psychiatry 1993;50: 151-156.
199. Dalman C, Allebeck P, Cullberg J, Grunewald C, Köster M. Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort. Arch Gen Psychiatry 1999;56:234-240.
200. Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ, et al. Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry 1999;56:162-168.
201. Kringlen E. Twin studies in schizophrenia with special emphasis on concordance figures. Am J Med Genet 2000;97:4-11.
202. Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991;148:1474-1486.
203. Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry 2003;160:13-23.
204. Gracie A, Freeman D, Green S, Garety PA, Kuipers E, Hardy A, et al. The association between traumatic experience, paranoia and hallucinations: a test of the predictions of psychological models. Acta Psychiatr Scand 2007;116:280-289.
205. Scott J, Chant D, Andrews G, Martin G, McGrath J. Association between trauma exposure and delusional experiences in a large community- based sample. Br J Psychiatry 2007;190:339-343.
206. D'Souza DC. Cannabinoids and psychosis. Int Rev Neurobiol 2007;78: 289-326.