Skip to main content
SpringerLink
Log in

Schizophrenia Spectrum Disorders and Risk for Cancer Morbidity and Mortality

  • Chapter
  • First Online:
Handbook of Schizophrenia Spectrum Disorders, Volume II

Abstract

This chapter reviews recent epidemiological studies on the relationship between schizophrenia spectrum disorders and cancer morbidity and mortality. Three sorts of findings are discussed: (1) reduced risk for cancer morbidity and mortality among patients diagnosed with schizophrenia and their first-degree relatives; (2) enhanced risk for cancer morbidity among patients with bipolar spectrum disorders, and (3) no increased risk for cancer morbidity among patients suffering from schizoaffective disorders. The genetic hypothesis suggests that the presence of genes with the dual effect of reducing the cancer risk and disrupting neurodevelopment is a plausible explanation for this association in schizophrenia patients. The environmental contributors to malignancy include health behavior, psychotropic medications, and metabolic syndrome, are suggested to explain the increased cancer risk among bipolar patients. The identification of risk and protective genes that mediate the development of malignant processes in some major psychiatric disorders is a new challenge in the field of psycho-oncology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

APC:

Adenomatous polyposis coli

CYP:

Cytochrome P450

MET:

MET proto-Oncogene

MspI:

A four base cutter (C decrease CGG) restriction endonuclease

MRS:

31p Nuclear magnetic resonance spectroscopy

PDK1:

3-Phosphoinositol-dependent kinase 1

PI3K:

Phosphatidylinositide 3-kinase

PKB:

Protein kinase B

PtIns3,4,5P3:

Phosphatidyl Inositol 3,4,5 triphosphate

NQO1:

NAD(P)H: Quinone oxidoreductase 1

SMR:

Standardized mortality ratio

SIR:

Standardized incidence ratio

PTEN:

Tumorsuppressor phosphatase with tensin homology

SOD:

Superoxide dismutase

SSRI:

Selective serotonin reuptake inhibitor

TGFBR2:

Transforming growth factor-B receptor

References

  1. Tandon R, Nasrallah HA, Keshavan MS (2009) Schizophrenia, “just the facts” 4. Clinical features and conceptualization. Schizophr Res 110:1–23

    PubMed  Google Scholar 

  2. Mueser KT, McGurk SR (2004) Schizophrenia. Lancet 363:2063–2072

    PubMed  Google Scholar 

  3. Crow TJ (1980) Positive and negative schizophrenic symptoms and the role of dopamine. Br J Psychiatry 137:383–386

    CAS  PubMed  Google Scholar 

  4. Andreasen NC, Olsen S (1982) Negative versus positive schizophrenia: definition and validation. Arch Gen Psychiatry 39:789–794

    CAS  PubMed  Google Scholar 

  5. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bul 13:261–276

    CAS  Google Scholar 

  6. Schultz SK, Andreasen NC (1999) Schizophrenia. Lancet 353:1425–1430

    CAS  PubMed  Google Scholar 

  7. Maki P, Veijola J, Jones PB et al (2005) Predictors of schizophrenia–a review. Br Med Bull 73:1–15

    PubMed  Google Scholar 

  8. Kendrick T (1996) Cardiovascular and respiratory risk factors and symptoms among general practice patients with long-term mental illness. Br J Psychiatry 169:733–739

    CAS  PubMed  Google Scholar 

  9. Brown S, Birtwistle J, Roe L, Thompson C (1999) The unhealthy lifestyle of people with schizophrenia. Psychol Med 29:697–701

    CAS  PubMed  Google Scholar 

  10. Dalack GW, Healy DJ, Meador-Woodruff JH (1998) Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings. Am J Psychiatry 155:1490–1501

    CAS  PubMed  Google Scholar 

  11. McCreadie RG, Kelly C (2000) Patients with schizophrenia who smoke. Private disaster, public resource [editorials]. Br J Psychiatry 176:109

    CAS  PubMed  Google Scholar 

  12. Kelly DL, McMahon RP, Wehring HJ et al (2009) Cigarette Smoking and Mortality Risk in People With Schizophrenia. Schizophr Bull Dec 17 [Epub ahead of print] doi: 10.1093/schbul/sbp152

    Google Scholar 

  13. Kavanagh DJ, McGrath J, Saunders JB et al (2002) Substance misuse in patients with schizophrenia: epidemiology and management. Drugs 62:743–755

    PubMed  Google Scholar 

  14. Batki SL, Meszaros ZS, Strutynski K et al (2009) Medical comorbidity in patients with schizophrenia and alcohol dependence. Schizophr Res 107:139–146

    PubMed  Google Scholar 

  15. Band PR, Le ND, MacArthur AC et al (2005) Identification of occupational cancer risks in British Columbia: a population-based case–control study of 1129 cases of bladder cancer. J Occup Environ Med 47:854–858

    CAS  PubMed  Google Scholar 

  16. Bender S, Grohmann R, Engel RR et al (2004) Severe adverse drug reactions in psychiatric inpatients treated with neuroleptics. Pharmacopsychiatry 37(1, suppl):46–53

    Google Scholar 

  17. Henderson DC (2007) Weight gain with atypical antipsychotics: evidence and insights. J Clin Psychiatry 68(12, suppl):18–26

    CAS  PubMed  Google Scholar 

  18. Kurzthaler I, Fleischhacker WW (2001) The clinical implications of weight gain in schizophrenia. J Clin Psychiatry 62(7, suppl):32–37

    CAS  PubMed  Google Scholar 

  19. Mortensen PB (1992) Neuroleptic medication and reduced risk of prostate cancer in schizophrenic patients. Acta Psychiatr Scand 85:390–393

    CAS  PubMed  Google Scholar 

  20. Bromley E (2007) Barriers to the appropriate clinical use of medications that improve the cognitive deficits of schizophrenia. Psychiatr Serv 58:475–481

    PubMed  Google Scholar 

  21. McCabe MP, Leas L (2008) A qualitative study of primary health care access, barriers and satisfaction among people with mental illness. Psychol Health Med 13:303–312

    PubMed  Google Scholar 

  22. Kerwin R (2009) Connecting patient needs with treatment management. Acta Psychiatr Scand 438(suppl):33–39

    Google Scholar 

  23. Koran LM, Sox HC Jr, Marton KI et al (1989) Medical evaluation of psychiatric patients. I. Results in a state mental health system. Arch Gen Psychiatry 46:733–740

    CAS  PubMed  Google Scholar 

  24. Felker B, Yazel JJ, Short D (1996) Mortality and medical comorbidity among psychiatric patients: a review. Psychiatr Serv 47:1356–1363

    CAS  PubMed  Google Scholar 

  25. Phelan M, Stradins L, Morrison S (2001) Physical health of people with severe mental illness. BMJ 322:443–444

    CAS  PubMed  Google Scholar 

  26. Jeste DV, Gladsjo JA, Lindamer LA, Lacro JP (1996) Medical comorbidity in schizophrenia. Schizophr Bull 22:413–430

    CAS  PubMed  Google Scholar 

  27. Grinshpoon A, Ponizovsky AM (2008) The relationships between need profiles, clinical symptoms, functioning and the well-being of inpatients with severe mental disorders. J Eval Clin Pract 14:218–225

    PubMed  Google Scholar 

  28. Awad AG, Voruganti LN (2008) The burden of schizophrenia on caregivers: a review. Pharmacoeconomics 26:149–162

    PubMed  Google Scholar 

  29. de Hert M, Schreurs V, Vancampfort D et al (2009) Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 8:15–22

    Google Scholar 

  30. McIntyre RS (2009) Understanding needs, interactions, treatment, and expectations among individuals affected by bipolar disorder or schizophrenia: the UNITE global survey. J Clin Psychiatry 70(3, suppl):5–11

    PubMed  Google Scholar 

  31. Levav I, Grinshpoon A (2004) Mental health services in Israel. Int Psychiatry 4:10–14

    Google Scholar 

  32. Cradock-O’Leary J, Young AS, Yano EM et al (2002) Use of general medical services by VA patients with psychiatric disorders. Psychiatr Serv 53:874–878

    PubMed  Google Scholar 

  33. Lindamer LA, Wear E, Sadler GR (2006) Mammography stages of change in middle-aged women with schizophrenia: an exploratory analysis. BMC Psychiatry 6:49–56

    PubMed  Google Scholar 

  34. Martens PJ, Chochinov HM, Prior HJ et al (2009) Are cervical cancer screening rates different for women with schizophrenia? A Manitoba population-based study. Schizophr Res 113:101–106

    PubMed  Google Scholar 

  35. Harris EC, Barraclough B (1998) Excess mortality of mental disorder. Br J Psychiatry 173:11–53

    CAS  PubMed  Google Scholar 

  36. Rantanen H, Koivisto AM, Salokangas RK et al (2009) Five-year mortality of Finnish schizophrenia patients in the era of deinstitutionalization. Soc Psychiatry Psychiatr Epidemiol 44:135–142

    PubMed  Google Scholar 

  37. Fox BH (1978) Cancer death risk in hospitalized mental patients. Science 201:966–968

    CAS  PubMed  Google Scholar 

  38. Iacovides A, Siamouli M (2008) Comorbid mental and somatic disorders: an epidemiological perspective. Curr Opin Psychiatry 21:417–421

    PubMed  Google Scholar 

  39. Carney CP, Woolson RF, Jones L et al (2007) Occurrence of cancer among people with mental health claims in an insured population. J Clin Psychiatry 68:917–923

    Google Scholar 

  40. Grinshpoon A, Barchana M, Ponizovsky A et al (2005) Cancer in schizophrenia: is the risk higher or lower?. Schizophr Res 73:333–341

    PubMed  Google Scholar 

  41. Gulbinat W, Dupont A, Jablensky A et al (1992) Cancer incidence of schizophrenic patients. Results of record linkage studies in three countries. Br J Psychiatry 161(18, suppl):75–83

    Google Scholar 

  42. Mortensen PB (1994) The occurrence of cancer in first admitted schizophrenic patients. Schizophr Res 12:185–194

    CAS  PubMed  Google Scholar 

  43. Lawrence D, Holman CD, Jablensky AV et al (2000) Excess cancer mortality in Western Australian psychiatric patients due to higher case fatality rates. Acta Psychiatr Scand 101:382–388

    CAS  PubMed  Google Scholar 

  44. Lichtermann D, Ekelund J, Pukkala E et al (2001) Incidence of cancer among persons with schizophrenia and their relatives. Arch Gen Psychiatry 58:573–578

    CAS  PubMed  Google Scholar 

  45. Cohen M, Dembling B, Schorling J (2002) The association between schizophrenia and cancer: a population-based mortality study. Schizophr Res 57:139–146

    PubMed  Google Scholar 

  46. Oksbjerg Dalton S, Munk Laursen T, Mellemkjaer L et al (2003) Schizophrenia and the risk for breast cancer. Schizophr Res 62:89–92

    PubMed  Google Scholar 

  47. Bushe CJ, Bradley AJ, Wildgust HJ et al (2009) Schizophrenia and breast cancer incidence: a systematic review of clinical studies. Schizophr Res 114:6–16

    PubMed  Google Scholar 

  48. Dupont A, Moller Jensen O, Stromgren E et al (1986) Incidence of cancer in patients diagnosed as schizophrenic in Denmark. In: Ten Horn GHMM, Giel R, Gulbinat WH, Henderson JH, eds. Psychiatric Case Registers in Public Health, Elsevier, Oxford, 229–239

    Google Scholar 

  49. Nakane Y, Ohta Y (1986) The example of a linkage with a cancer register. In: Ten Horn GHMM, Giel R, Gulbinat WH, Henderson JH, eds. Psychiatric Case Registers in Public Health, Elsevier, Oxford, 240–245

    Google Scholar 

  50. Mortensen PB (1989) The incidence of cancer in schizophrenic patients. J Epidemiol Commun Health 43:43–47

    CAS  Google Scholar 

  51. Barak Y, Achiron A, Mandel M et al (2005) Reduced cancer incidence among patients with schizophrenia. Cancer 104:2817–2821

    PubMed  Google Scholar 

  52. Dalton SO, Mellemkjaer L, Thomassen L et al (2005) Risk for cancer in a cohort of patients hospitalized for schizophrenia in Denmark, 1969-1993. Schizophr Res 75:315–324

    PubMed  Google Scholar 

  53. Goldacre MJ, Kurina LM, Wotton CJ et al (2005) Schizophrenia and cancer: an epidemiological study. Br J Psychiatry 187:334–338

    PubMed  Google Scholar 

  54. Hippisley-Cox J, Vinogradova Y, Coupland C et al (2007) Risk of malignancy in patients with schizophrenia or bipolar disorder: nested case-control study. Arch Gen Psychiatry 64:1368–1376

    PubMed  Google Scholar 

  55. Barak Y, Levy T, Achiron A et al (2008) Breast cancer in women suffering from serious mental illness. Schizophr Res 102:249–253

    PubMed  Google Scholar 

  56. Kelsey JL (1993) Breast cancer epidemiology. Epidemiol Rev 15:256–263

    CAS  PubMed  Google Scholar 

  57. Krieger N (1990) Social class and the black/white cross-over in the age-specific incidence of breast cancer: a study linking census-derived data to population based registry records. Am J Epidemiol 131:804–814

    CAS  PubMed  Google Scholar 

  58. Bodian CA (1993) Benign breast diseases, carcinoma in situ, and breast cancer risk. Epidemiol Rev 15:177–187

    CAS  PubMed  Google Scholar 

  59. Hunter DJ, Willett WC (1993) Diet, body size and breast cancer. Epidemiol Rev 15:110–132

    CAS  PubMed  Google Scholar 

  60. Horn-Ross PL (1993) Multiple primary cancers involving the breast. Epidemiol Rev 15:169–176

    CAS  PubMed  Google Scholar 

  61. Torrey EF (2006) Prostate cancer and schizophrenia. Urology 68:1280–1283

    PubMed  Google Scholar 

  62. Bhui K, Puffet A, Strathdee G (1997) Sexual and relationship problems amongst patients with severe chronic psychoses. Soc Psychiatry Psychiatr Epidemiol 32:459–467

    CAS  PubMed  Google Scholar 

  63. Fortier P, Mottard J-P, Trudel G et al (2003) Study of sexuality-related characteristics in young adults with schizophrenia treated with novel neuroleptics and in a comparison group of young adults. Schizophr Bull 29:559–572

    PubMed  Google Scholar 

  64. Levav I, Lipshitz I, Novikov I et al (2007) Cancer risk among parents and siblings of patients with schizophrenia. Br J Psychiatry 190:156–161

    CAS  PubMed  Google Scholar 

  65. Catts VS, Catts SV, O_Toole BI et al (2008) Cancer incidence in patients with schizophrenia and their first-degree relatives – a metaanalysis. Acta Psychiatr Scand 117:323–336

    CAS  PubMed  Google Scholar 

  66. Preti A (2008) Reduced risk of cancer in schizophrenia: a role for obstetric complications? [letter]. Acta Psychiatr Scand 118:251–253

    PubMed  Google Scholar 

  67. Catts VS, Catts SV (2000) Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene?. Schizophr Res 41:405–415

    CAS  PubMed  Google Scholar 

  68. Jablensky A, Lawrence D (2001) Schizophrenia and cancer: is there a need to invoke a protective gene?. Arch Gen Psychiatry 58:579–580

    CAS  PubMed  Google Scholar 

  69. Carney CP, Jones LE (2006) Medical comorbidity in women and men with bipolar disorders: A population-based controlled study. Psychosom Med 68:684–691

    PubMed  Google Scholar 

  70. Barchana M, Levav I, Lipshitz I et al (2008) Enhanced cancer risk among patients with bipolar disorder. J Affect Disord 108:43–48

    PubMed  Google Scholar 

  71. Levav I, Kohn R, Barchana M et al (2009) The risk for cancer among patients with schizoaffective disorders. J Affect Disord 114:316–320

    PubMed  Google Scholar 

  72. Kroenke CH, Bennett GG, Fuchs C et al (2005) Depressive symptoms and prospective incidence of colorectal cancer in women. Am J Epidemiol 162:839–848

    PubMed  Google Scholar 

  73. Nyklícek I, Louwman WJ, Van Nierop PW et al (2003) Depression and the lower risk for breast cancer development in middle-aged women: a prospective study. Psychol Med 33:1111–1117

    PubMed  Google Scholar 

  74. Osborn DPJ, Levy G, Nazareth I et al (2007) Relative risk of cardiovascular and cancer mortality in people with severe mental illness from the United Kingdom’s General Practice Research Database. Arch Gen Psychiatry 64:242–249

    PubMed  Google Scholar 

  75. Kisely S, Sadek J, MacKenzie A et al (2008) Excess cancer mortality in psychiatric patients. Can J Psychiatry 53:753–761

    PubMed  Google Scholar 

  76. Tran E, Rouillon F, Loze JY et al (2009) Cancer mortality in patients with schizophrenia: an 11-year prospective cohort study. Cancer 115:3555–3562

    PubMed  Google Scholar 

  77. Capasso RM, Lineberry TW, Bostwick JM et al (2008) Mortality in schizophrenia and schizoaffective disorder: an Olmsted County, Minnesota cohort: 1950-2005. Schizophr Res 98:287–294

    PubMed  Google Scholar 

  78. Kirkpatrick B, Messias E, Harvey PD et al (2008) Is schizophrenia a syndrome of accelerated aging?. Schizophr Bull 34:1024–1032

    PubMed  Google Scholar 

  79. Arnold SE, Talbot K, Hahn CG (2005) Neurodevelopment, neuroplasticity, and new genes for schizophrenia. Prog Brain Res 147:319–345

    CAS  PubMed  Google Scholar 

  80. Kendler KS (2005) “A gene for...”: the nature of gene action in psychiatric disorders. Am J Psychiatry 162:1243–1252

    PubMed  Google Scholar 

  81. Tabarés-Seisdedos R, Rubenstein JL (2009) Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry 14:563–589

    PubMed  Google Scholar 

  82. Park JK, Lee HJ, Kim JW et al (2004) Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients. Schizophr Res 67:71–74

    CAS  PubMed  Google Scholar 

  83. Cui DH, Jiang KD, Jiang SD et al (2005) The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia. Mol Psychiatry 10:669–677

    CAS  PubMed  Google Scholar 

  84. Numata S, Ueno S, Iga J et al (2008) TGFBR2 gene expression and genetic association with schizophrenia. J Psychiatr Res 42:425–432

    PubMed  Google Scholar 

  85. Hainaut P, Hollstein M (2000) p53 and human cancer: the first ten thousand mutations. Adv Cancer Res 77:81–137

    CAS  PubMed  Google Scholar 

  86. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    CAS  PubMed  Google Scholar 

  87. Kastan M (2007) Wild-type p53: tumors can’t stand it. Cell 128:837–840

    CAS  PubMed  Google Scholar 

  88. Plummer NW, Gallione CJ, Srinivasan S et al (2004) Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations. Am J Pathol 165:1509–1518

    CAS  PubMed  Google Scholar 

  89. Yoon H, Liyanarachchi S, Wright FA et al (2002) Gene expression profiling of isogenic cells with different TP53 gene dosage reveals numerous genes that are affected by TP53 dosage and identifies CSPG2 as a direct target of p53. Proc Natl Acad Sci USA 99:15632–15637

    CAS  PubMed  Google Scholar 

  90. Chiu HJ, Wang YC, Chen JY et al (2001) Association study of the p53-gene Pro72Arg polymorphism in schizophrenia. Psychiatry Res 105:279–283

    CAS  PubMed  Google Scholar 

  91. Papiol S, Arias B, Barrantes-Vidal N et al (2004) Analysis of polymorphisms at the tumor suppressor gene p53 (TP53) in contributing to the risk for schizophrenia and its associated neurocognitive deficits. Neurosci Lett 363:78–80

    CAS  PubMed  Google Scholar 

  92. Yang Y, Xiao Z, Chen W et al (2004) Tumor suppressor gene TP53 is genetically associated with schizophrenia in the Chinese population. Neurosci Lett 369:126–131

    CAS  PubMed  Google Scholar 

  93. Ni X, Trakalo J, Valente J et al (2005) Human p53 tumor suppressor gene (TP53) and schizophrenia: case-control and family studies. Neurosci Lett 388:173–178

    CAS  PubMed  Google Scholar 

  94. Tabare´s-Seisdedos R, Esca´mez T, Martı´nez-Gime´nez JA et al (2006) Variations in genes regulating neuronal migration predict reduced prefrontal cognition in schizophrenia and bipolar subjects from mediterranean Spain: a preliminary study. Neuroscience 139:1289–1300

    Google Scholar 

  95. Cully M, You H, Levine AJ et al (2006) Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6:184–192

    CAS  PubMed  Google Scholar 

  96. van Diepen MT, Eickholt BJ (2008) Function of PTEN during the formation and maintenance of neuronal circuits in the brain. Dev Neurosci 30:59–64

    PubMed  Google Scholar 

  97. Avogaro A, de Kreutzenberg SV, Fadini GP (2008) Oxidative stress and vascular disease in diabetes: is the dichotomization of insulin signaling still valid?. Free Radic Biol Med 44:1209–1215

    CAS  PubMed  Google Scholar 

  98. Thiselton DL, Vladimirov VI, Kuo PH et al (2008) AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish study of high-density schizophrenia families. Biol Psychiatry 63:449–457

    CAS  PubMed  Google Scholar 

  99. Asher G, Lotem J, Kama R, Sachs L, Shaul Y (2002) NQO1 stabilizes p53 through a distinct pathway. Proc Natl Acad Sci USA 99:3099–3104

    CAS  PubMed  Google Scholar 

  100. Fagerholm R, Hofstetter B, Tommiska J et al (2008) NAD(P)H: quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nat Genet 40:844–853

    CAS  PubMed  Google Scholar 

  101. Usadel H, Brabender J, Danenberg KD et al (2002) Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Res 62:371–375

    CAS  PubMed  Google Scholar 

  102. Harder J, Opitz OG, Brabender J et al (2008) Quantitative promoter methylation analysis of hepatocellular carcinoma, cirrhotic and normal liver. Int J Cancer 122:2800–2804

    CAS  PubMed  Google Scholar 

  103. Burdick KE, DeRosse P, Kane JM et al (2010) Association of genetic variation in the MET proto-oncogene with schizophrenia and general cognitive ability. Am J Psychiatry 167:436–443

    PubMed  Google Scholar 

  104. Cannon TD (2010) Candidate Gene Studies in the GWAS Era: The MET Proto-Oncogene, Neurocognition, and Schizophrenia. Am J Psychiatry 167:369–372

    PubMed  Google Scholar 

  105. Kalkman HO (2006) The role of the phosphatidylinositide 3-kinase-protein kinase B pathway in schizophrenia. Pharmacol Ther 110:117–134

    CAS  PubMed  Google Scholar 

  106. Brazil DP, Hemmings BA (2001) Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci 26:657–664

    CAS  PubMed  Google Scholar 

  107. Asnaghi L, Bruno P, Priulla M et al (2004) mTOR: a protein kinase switching between life and death. Pharmacol Res 50:545–549

    CAS  PubMed  Google Scholar 

  108. Glantz LA, Lewis DA (2000) Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 57:65–73

    CAS  PubMed  Google Scholar 

  109. Law MH, Cotton RG, Berger GE (2006) The role of phospholipases A2 in schizophrenia. Mol Psychiatry 11:547–556

    CAS  PubMed  Google Scholar 

  110. Ellert-Miklaszewska A, Kaminska B, Konarska L (2005) Cannabinoids down-regulate PI3K/Akt and Erk signaling pathways and activate proapoptotic function of Bad protein. Cell Signal 17:25–37

    CAS  PubMed  Google Scholar 

  111. Akhondzadeh S, Nejatisafa AA, Amini H et al (2003) Adjunctive estrogen treatment in women with chronic schizophrenia: a double blind, randomized, and placebo-controlled trial. Prog Neuro-Psychopharmacol Biol Psychiatry 27:1007–1012

    CAS  Google Scholar 

  112. McGrath J, Saari K, Hakko H et al (2004) Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res 67:237–245

    PubMed  Google Scholar 

  113. Kang UG, Roh MS, Jung JR et al (2004) Activation of protein kinase B (Akt) signaling after electroconvulsive shock in the rat hippocampus. Prog Neuro-sychopharmacol Biol Psychiatry 28:41–44

    CAS  Google Scholar 

  114. Alimohamad H, Rajakumar N, Seah YH et al (2005) Antipsychotics alter the protein expression levels of h-catenin and GSK-3 in the rat medial prefrontal cortex and striatum. Biol Psychiatry 57:533–542

    CAS  PubMed  Google Scholar 

  115. Isohanni M, Lauronen E, Moilanen K et al (2005) Predictors of schizophrenia: evidence from the Northern Finland 1966 Birth Cohort and other sources. Br J Psychiatry 187(48, suppl):s4–7

    Google Scholar 

  116. Clarke MC, Harley M, Cannon M (2006) The role of obstetric events in schizophrenia. Schizophr Bull 32:3–8

    PubMed  Google Scholar 

  117. Rosen CJ (1999) Serum insulin-like growth factors and insulin-like growth factor-binding proteins: clinical implications. Clin Chem 45:1384–1390

    CAS  PubMed  Google Scholar 

  118. Lofqvist C, Andersson E, Gelander L et al (2001) Reference values for IGF-1 throughout childhood and adolescence: a model that accounts simultaneously for the effect of gender, age, and puberty. J Clin Endocrinol Metab 86:5870–5976

    CAS  PubMed  Google Scholar 

  119. Moon RT, Bowerman B, Boutros M et al (1646) The promise and perils of Wnt signaling through h-catenin. Science 2002(296):1644–1646

    Google Scholar 

  120. Osaki M, Oshimura M, Ito H (2004) PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9:667–676

    CAS  PubMed  Google Scholar 

  121. Glantz LA, Gilmore JH, Lieberman JA, Jarskog LF (2006) Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res. 81(1):47–63

    PubMed  Google Scholar 

  122. Coultas L, Strasser A (2000) The molecular control of DNA damage-induced cell death. Apoptosis 5:491–507

    CAS  PubMed  Google Scholar 

  123. Gerl R, Vaux DL (2005) Apoptosis in the development and treatment of cancer. Carcinogenesis 26:263–270

    CAS  PubMed  Google Scholar 

  124. Sastry PS, Rao KS (2000) Apoptosis and the nervous system. J Neurochem 74:1–20

    CAS  PubMed  Google Scholar 

  125. Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cyt 68:251– 306

    CAS  Google Scholar 

  126. Bredesen DE (1995) Neural apoptosis. Ann Neurol 38:839–851

    CAS  PubMed  Google Scholar 

  127. Oppenheim RW (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14:453–501

    CAS  PubMed  Google Scholar 

  128. Arnold SE (1999) Neurodevelopmental abnormalities in schizophrenia: insights from neuropathology. Dev Psychopathol 11:439–456

    CAS  PubMed  Google Scholar 

  129. Mala E (2008) Schizophrenia in childhood and adolescence. Neuro Endocrinol Lett 29:831–836

    PubMed  Google Scholar 

  130. Burek MJ, Oppenheim RW (1996) Programmed cell death in the developing nervous system. Brain Pathol 6:427–446

    CAS  PubMed  Google Scholar 

  131. Mattson MP, Duan W, Pedersen WA et al (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6:69–81

    CAS  PubMed  Google Scholar 

  132. Morrison RS, Kinoshita Y, Johnson MD et al (2003) p53-dependent cell death signaling in neurons. Neurochem Res 28:15–27

    CAS  PubMed  Google Scholar 

  133. Camandola S, Mattson MP (2000) Pro-apoptotic action of PAR-4 involves inhibition of NF-kappaB activity and suppression of BCL-2 expression. J Neurosci Res 61:134–139

    CAS  PubMed  Google Scholar 

  134. Mahadik SP, Evans D, Lal H (2001) Oxidative stress and role of antioxidant and omega- 3 essential fatty acid supplementation in schizophrenia. Prog Neuro-psychopharmacol Biol Psychiatry 25:463–493

    CAS  Google Scholar 

  135. Mukerjee S, Mahadik SP, Scheffer R et al (1996) Impaired antioxidant defense at the onset of psychosis. Schizophr Res 19:19–26

    CAS  PubMed  Google Scholar 

  136. Horrobin DF (1998) The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental concept of schizophrenia. Schizophr Res 30:193–208

    CAS  PubMed  Google Scholar 

  137. Ponizovsky AM, Modai I, Nechamkin Y et al (2001) Phospholipid patterns of erythrocytes in schizophrenia: relationships to symptomatology. Schizophr Res 52:121–126

    CAS  PubMed  Google Scholar 

  138. Ponizovsky AM, Barshtein G, Bergelson LD (2003) Biochemical alterations of erythrocytes as an indicator of mental disorders: an overview. Harv Rev Psychiatry 11:317–332

    PubMed  Google Scholar 

  139. Pettegrew JW, Keshavan MS, Minshew NJ (1993) 31P nuclear magnetic resonance spectroscopy: neurodevelopment and schizophrenia. Schizophr Bull 19:35–53

    CAS  PubMed  Google Scholar 

  140. Csatary LK (1972) Chlorpromazines and cancer. Lancet 2:338–339

    CAS  PubMed  Google Scholar 

  141. Driscoll JS, Melnick NR, Quinn FR et al (1978) Psychotropic drugs as potential antitumor agents: a selective screening study. Cancer Treat Rep 62:45–59

    CAS  PubMed  Google Scholar 

  142. Nordenberg J, Fenig E, Landau M et al (1999) Effects of psychotropic drugs on cell proliferation and differentiation. Biochem Pharmacol 58:1229–1236

    CAS  PubMed  Google Scholar 

  143. Nordenberg J, Perlmutter I, Lavie G et al (2005) Anti-proliferative activity of haloperidol in B16 mouse and human SK-MEL-28 melanoma cell lines. Int J Oncol 27:1097–1103

    CAS  PubMed  Google Scholar 

  144. Gil-Ad I, Shtaif B, Shiloh R et al (2001) Evaluation of the neurotoxic activity of typical and atypical neuroleptics: relevance to iatrogenic extrapyramidal symptoms. Cell Mol Neurobiol 21:705–716

    CAS  PubMed  Google Scholar 

  145. Gil-Ad I, Shtaif B, Levkovitz Y et al (2004) Characterization of phenothiazine-induced apoptosis in neuroblastoma and glioma cell lines: clinical relevance and possible application for brain-derived tumors. J Mol Neurosci 22:189–198

    CAS  PubMed  Google Scholar 

  146. Gil-Ad I, Shtaif B, Levkovitz Y et al (2006) Phenothiazines induce apoptosis in a B16 mouse melanoma cell line and attenuate in vivo melanoma tumor growth. Oncol Rep 15:107–112

    CAS  PubMed  Google Scholar 

  147. Carrillo JA, Benítez J (1999) Are antipsychotic drugs potentially chemopreventive agents for cancer?. Eur J Clin Pharmacol 55:487–488

    CAS  PubMed  Google Scholar 

  148. Dickson RA, Glazer WM (1999) Neuroleptic-induced hyperprolactinemia. Schizophr Res 35(suppl):S75–S86

    PubMed  Google Scholar 

  149. Schyve PM, Smithline F, Meltzer HY (1978) Neuroleptic-induced prolactin level elevation and breast cancer. Arch Gen Psychiatry 35:1291–1301

    CAS  PubMed  Google Scholar 

  150. Welsch CW, Nagasawa H (1977) Prolactin and murine mammary tumorigenesis: a review. Cancer Res 37:951–963

    CAS  PubMed  Google Scholar 

  151. Duncan KL, Don BR, Schaeffer LD (1977) An introductory study of the influence and role of prolactin in mammary tumor growth. Proc West Pharmacol Soc 20:195–197

    CAS  PubMed  Google Scholar 

  152. Pearson OH, Llerena O, Llerena L (1969) Prolactin-dependent rat mammary cancer: a model for man?. Trans Assoc Am Physicians 82:225–238

    CAS  PubMed  Google Scholar 

  153. Forrest DA (1972) Introduction: prolactin, the pituitary and breast cancer. In: Boyns AR, Griffiths K, eds. Fourth Tenovus Workshop on Prolactin and Carcinogenesis, Alpha Omega Alpha Publishing, Cardiff, Wales, 124–127

    Google Scholar 

  154. Wang PS, Walker AM, Tsuang MT et al (2002) Dopamine antagonists and the development of breast cancer. Arch Gen Psychiatry 59:1147–1154

    CAS  PubMed  Google Scholar 

  155. Theoharides TC, Konstantinidou A (2003) Antidepressants and risk of cancer: a case of misguided associations and priorities. J Clin Psychopharmacol 23:1–4

    PubMed  Google Scholar 

  156. Cotterchio M, Kreiger N, Darlington G et al (2000) Antidepressant medication use and breast cancer risk. Am J Epidemiol 151:951–957

    CAS  PubMed  Google Scholar 

  157. Traub M Antidepressants (SSRIs) may increase breast cancer risk. Proc. 35th Annual Meeting Society for Epidemiologic Research, June 19–21, 2000, Seattle, Washington, DC

    Google Scholar 

  158. Marx J (1992) Do antidepressants promote tumors?. [letter] Science 257:22–23

    CAS  Google Scholar 

  159. Miller LG (1993) Antidepressants and cancer: cause for concern?. J Clin Psychopharmacol 13:1–2

    CAS  PubMed  Google Scholar 

  160. Brink S (1995) A different kind of cancer risk. U S News & World Report 9:58–61

    Google Scholar 

  161. Brandes LJ, Arron RJ, Bogdanovic RP et al (1992) Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. Cancer Res 52:3796–3800

    CAS  PubMed  Google Scholar 

  162. Brandes LJ, Warrington RC, Arron RJ et al (1994) Enhanced cancer growth in mice administered daily human-equivalent doses of some H1-antihistamines: predictive in vitro correlates. J Natl Cancer Inst 86:770–775

    CAS  PubMed  Google Scholar 

  163. Iishi H, Tatsuta M, Baba M et al (1840) Enhancement by the tricyclic antidepressant, desipramine of experimental carcinogenesis in rat colon indused by azoxymethane. Carcinogenesis 1993(14):1837–1840

    Google Scholar 

  164. Wright SC, Zhong J, Larrick JW (1994) Inhibition of apoptosis as a mechanism of tumor promotion. FASEB J 8:654–660

    CAS  PubMed  Google Scholar 

  165. Bendele RA, Adams ER, Hoffman WP et al (1992) Carcinogenicity studies of fluoxetine hydrochloride in rats and mice. Cancer Res 52:6391–6395

    Google Scholar 

  166. Brandes LJ, Macdonald LM, Bogdanovic RP (1985) Evidence that the antiestrogen binding site is a histamine or histamine-like receptor. Biochem Biophys Res Commun 126:905–910

    CAS  PubMed  Google Scholar 

  167. Siegel JN, Schwartz A, Askenase PW et al (1982) T-cell suppression and contrasuppression induced by histamine H2 and H1 receptor agonists, respectively. Proc Natl Acad Sci USA 79:5052–5056

    CAS  PubMed  Google Scholar 

  168. Steingart AB, Cotterchio M (1995) Do antidepressants cause, promote, or inhibit cancers?. J Clin Epidemiol 48:1407–1412

    CAS  PubMed  Google Scholar 

  169. Levkovitz Y, Gil-Ad I, Zeldich E et al (2005) Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: evidence for p-c-Jun, cytochrome c, and caspase-3 involvement. J Mol Neurosci 27:29–42

    CAS  PubMed  Google Scholar 

  170. Gil-Ad I, Zolokov A, Lomnitski L et al (2008) Evaluation of the potential anti-cancer activity of the antidepressant sertraline in human colon cancer cell lines and in colorectal cancer-xenografted mice. Int J Oncol 33:277–286

    CAS  PubMed  Google Scholar 

  171. Amit BH, Gil-Ad I, Taler M et al (2009) Proapoptotic and chemosensitizing effects of selective serotonin reuptake inhibitors on T cell lymphoma/leukemia (Jurkat) in vitro. Eur Neuropsychopharmacol 19:726–734

    CAS  PubMed  Google Scholar 

  172. Bassukas ID (1994) Effect of amitriptylline on the growth kinetics of two human cancer xenograft lines in nude mice. Int J Oncol 4:977–982

    CAS  Google Scholar 

  173. Hisaoka K, Nishida A, Koda T et al (2001) Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. J Neurochem 79:25–34

    CAS  PubMed  Google Scholar 

  174. Bartholeyns J, Fozard JR (1985) Role of histamine in tumor development. TIPS 6:123–125

    CAS  Google Scholar 

  175. Nordlund JJ, Askenase PW (1983) The effect of histamine, antihistamines and a mast cell stabilizer on the growth of Cloudman melanoma cells in DBA/2 mice. J Invest Dermatol 81:28–31

    CAS  PubMed  Google Scholar 

  176. Brandes LJ, LaBella FS, Warrington RC (1991) Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists. J Natl Cancer Inst 83:1329–1336

    CAS  PubMed  Google Scholar 

  177. Sudo K, Monsma J, Katzenellenbogen BS (1983) Antiestrogen binding sites distinct from the estrogen receptor: subcellular localization, ligand specificity, and distribution in tissues of the rat. Endocrinology 112:425–434

    CAS  PubMed  Google Scholar 

  178. Brandes LJ, Bogdanovic RP (1986) New evidence that the antiestrogen binding site may be a novel growth-promoting histamine receptor (?H3) which mediates the antiestrogenic and antiproliferative effects of tamoxifen. Biochem Biophys Res Commun 134:601–608

    CAS  PubMed  Google Scholar 

  179. Middleton E, Kandaswami C, Theoharides TC (2000) The effects of plant flavonoids on mammalian cells:Implications for inflammation, heart disease and cancer. Pharmacol Rev 52:673–751

    CAS  PubMed  Google Scholar 

  180. Theoharides TC, Alexandrakis M, Kempuraj D et al (2001) Anti-inflammatory actions of flavonoids and structural requirements for new design. Int J Immunopath Pharmacol 14:119–127

    CAS  Google Scholar 

  181. Brandes LJ, Bracken SP, Ramsey EWN (1995) N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine in combination with cyclophosphamide: an active, low-toxicity regiment for metastatic hormonally unresponsive prostate cancer. J Clin Oncol 13:1398–1403

    CAS  PubMed  Google Scholar 

  182. Crowson AN, Magro CM (1995) Antidepressant therapy: a possible cause of atypical cutaneous lymphoid hyperplasia. Arch Dermatol 131:925–929

    CAS  PubMed  Google Scholar 

  183. Magro CM, Crowson AN (1995) Drugs with antihistaminic properties as a cause of atypical cutaneous lymphoid hyperplasia. J Am Acad Dermatol 32:419–428

    CAS  PubMed  Google Scholar 

  184. Kunkel EJ, Woods CM, Rodgers C et al (1997) Consultations for “maladaptive denial of illness” in patients with cancer: psychiatric disorders that result in noncompliance. Psychooncology 6:139–149

    CAS  PubMed  Google Scholar 

  185. Lohr JB, Flynn K (1992) Smoking and schizophrenia. Schizophr Res 8:93–102

    CAS  PubMed  Google Scholar 

  186. Kanakry CG, Li Z, Nakai Y, Sei Y, Weinberger DR (2007) Neuregulin-1 regulates cell adhesion via an ErbB2/phosphoinositide-3 kinase/Akt-dependent pathway: potential implications for schizophrenia and cancer. PLoS One 2:e1369

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mental Health Services, Ministry of Health, Jerusalem, Israel

    Alexander M. Ponizovsky

  2. Geha Mental Health Center and Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel

    Abraham Weizman

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Abraham Weizman

  4. Sha’ar Menashe Mental Health Center, Ministry of Health, Hadera, Israel

    Alexander Grinshpoon

Authors
  1. Alexander M. Ponizovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abraham Weizman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander Grinshpoon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander M. Ponizovsky .

Editor information

Editors and Affiliations

  1. , Rappaport Faculty of Medicine, Technion - Israel Institute of Technolog, Haifa, Israel

    Michael Ritsner

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Ponizovsky, A.M., Weizman, A., Grinshpoon, A. (2011). Schizophrenia Spectrum Disorders and Risk for Cancer Morbidity and Mortality. In: Ritsner, M. (eds) Handbook of Schizophrenia Spectrum Disorders, Volume II. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0831-0_19

Download citation

Publish with us

Policies and ethics

Search

Navigation