Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-24T00:27:05.957Z Has data issue: false hasContentIssue false
  • English
  • Français

A public health genetic approach for schizophrenia

Published online by Cambridge University Press:  18 May 2011

Andrea Danese
Andrea Danese*
Affiliation:
Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London (United Kingdom)
*
Address for correspondence: Dr. A. Danese, PO 080, De Crespigny Park, Denmark Hill, London SE5 8AF (United Kingdom). Fax: +44-0- 20-7848.0866 E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Background – Schizophrenia is a complex disease resulting from the interplay of genetic and environmental factors. However, psychiatric genetics and epidemiology have often worked as independent research fields. Aims – To review the evidence about the gene-environment interplay involved in the development of schizophrenia. Methods – Systematic review of medical and psychological databases. Results – On one hand, quantitative and molecular genetics showed high heritability for schizophrenia and identified genes likely to be involved in its pathophysiology. The strength of the association between candidate genes and schizophrenia is however modest, and the need for a more appropriate conceptualization of the genetic risk has been claimed. On the other hand, psychiatric epidemiology described several environmental factors liked with the onset or the course of schizophrenia. The observational nature of epidemiology, however, may hamper inference on causation. Gene-environment correlations and interactions influence the exposure and the vulnerability to the environment, respectively. Current findings suggest that gene-environment correlations and interactions may be common phenomena in the pathophysiology of schizophrenia. The consideration of gene-environment interplay may help to overcome many limitations of genetic and epidemiological studies in psychiatry and suggest innovative preventive and therapeutic strategies. Conclusions – Taking into account the complexity of schizophrenia pathophysiology, mental health genetics may provide a comprehensive and heuristic model of disease.

Declaration of Interest: none.

Keywords

schizophreniaepidemiologygeneticsmental health genetics.
Type
Special Articles
Information
Epidemiology and Psychiatric Sciences , Volume 15 , Issue 3 , September 2006 , pp. 185 - 193
Copyright
Copyright © Cambridge University Press 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Abdolmaleky, H.M., Smith, C.L., Faraone, S.V., Shafa, R., Stone, W., Glatt, S.J. & Tsuang, M.T. (2004). Methylomics in psychiatry: Modulation of gene-environment interactions may be through DNA methylation. American Journal of Medical Genetetics 127B, 51–59.CrossRefGoogle ScholarPubMed
Andreasen, N. C. (1999). Understanding the causes of schizophrenia. New England Journal of Medicine 340, 645–647.CrossRefGoogle ScholarPubMed
Arseneault, L., Cannon, M., Witton, J. & Murray, R. M. (2004). Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry 184, 110–117.CrossRefGoogle ScholarPubMed
Badner, J.A. & Gershon, E.S. (2002). Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Molecular Psychiatry 1, 405–411.CrossRefGoogle Scholar
Bell, J. (2004). Predicting disease using genomics. Nature 429, 453–456.CrossRefGoogle ScholarPubMed
Bell, R.Q. (1968). A reinterpretation of the direction of effects in studies of socialization. Psychological Review 75, 81–95.CrossRefGoogle ScholarPubMed
Bennedsen, B.E., Mortensen, P.B., Olesen, A.V. & Henriksen, T.B. (2001). Congenital malformations, stillbirths, and infant deaths among children of women with schizophrenia. Archives of General Psychiatry 58, 674–679.CrossRefGoogle ScholarPubMed
Burke, W. (2003). Genomics as a probe for disease biology. New-England Journal of Medicine 349, 969–974.CrossRefGoogle ScholarPubMed
Butzlaff, R.L. & Hooley, J.M. (1998). Expressed emotion and psychiatric relapse: a meta-analysis. Archives of General Psychiatry 55, 547–552.CrossRefGoogle ScholarPubMed
Cannon, M., Jones, P.B. & Murray, R.M. (2002). Obstetric complications and schizophrenia: historical and meta-analytic review. American Journal of Psychiatry 159, 1080–1092.CrossRefGoogle ScholarPubMed
Cannon, T.D. (1996). Abnormalities of brain structure and function in schizophrenia: implications for aetiology and pathophysiology. Annals of Medicine 28, 533–539.CrossRefGoogle ScholarPubMed
Cantor-Graae, E. & Selten, J.P. (2005). Schizophrenia and migration: a meta-analysis and review. American Journal of Psychiatry 162, 12–24.CrossRefGoogle ScholarPubMed
Caspi, A., Sugden, K., Moffitt, T.E., Taylor, A., Craig, I.W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A. & Poulton, R. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386–389.CrossRefGoogle ScholarPubMed
Caspi, A., Moffitt, T.E., Cannon, M., McClay, J., Murray, R., Harrington, H., Taylor, A., Arseneault, L., Williams, B., Braithwaite, A., Poulton, R. & Craig, I.W. (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biological Psychiatry 57, 1117–1127.CrossRefGoogle ScholarPubMed
Champagne, F.A. & Curley, J.P. (2005). How social experiences influence the brain. Current Opinion in Neurobiology 15, 704–709.CrossRefGoogle ScholarPubMed
Clayton, D. & McKeigue, P.M. (2001). Epidemiological methods for studying genes and environmental factors in complex diseases. Lancet 35, 1356–1360.CrossRefGoogle Scholar
Clayton, E.W. (2003). Ethical, legal, and social implications of genomie medicine. New England Journal of Medicine 349, 562–569.CrossRefGoogle Scholar
Cooper, B. (2005). Schizophrenia, social class and immigrant status: the epidemiological evidence. Epidemiologia e Psichiatria Sociale 14, 137–144.CrossRefGoogle ScholarPubMed
Cotter, D. & Pariante, C.M. (2002). Stress and the progression of the developmental hypothesis of schizophrenia. British Journal of Psychiatr 181, 363–365.CrossRefGoogle ScholarPubMed
D'Souza, D.C., Perry, E., MacDougall, L., Ammerman, Y., Cooper, T., Wu, Y.T., Braley, G., Gueorguieva, R. & Krystal, J.H. (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29, 1558–1572.CrossRefGoogle ScholarPubMed
Dawkins, R. (1982). The Extended Phenotype: the Gene as Unit of Selection. Oxford University Press: Oxford.Google Scholar
Dawkins, R. (1989). The Selfish Gene. Oxford University Press: Oxford.Google Scholar
Di Forti, M. & Murray, R. M. (2005). Cannabis consumption and risk of developing schizophrenia: myth or reality? Epidemiologia e Psichiatria Sociale 14, 184–187.CrossRefGoogle ScholarPubMed
Dohrenwend, B.P. & Dohrenwend, B. S. (1969). Social Status and Psychological Disorders: a Causal Inquiry. John Wiley & Sons: New York.Google Scholar
Dohrenwend, B.P., Levav, I., Shrout, P.E., Schwartz, S., Naveh, G., Link, B.G., Skodol, A.E. & Stueve, A. (1992). Socioeconomic status and psychiatric disorders: the causation-selection issue. Science 255, 946–952.CrossRefGoogle ScholarPubMed
Eaton, W.W., Day, R. & Kramer, M. (1988). The use of epidemiology for risk factor research in schizophrenia: an overview and methodological critique. In Handbook of Schizophrenia, vol. 3: Nosology, Epidemiology and Genetics of Schizophrenia (ed. Tsuang, M. and Simpson, J. C.), pp. 169–204. Elsevier: New York.Google Scholar
Garrod, A. (1902). The incidence of alkaptonuria: a study in chemical individuality. Lancet 2, 1616?71620.CrossRefGoogle Scholar
Goldman, N. (1994). Social factors and health: the causation-selection issue revisited. Proceedings of the National Academy of Sciences of the United States of America 91, 1251–1255.CrossRefGoogle ScholarPubMed
Goldstein, M.J. (1994). Psychoeducational and family therapy in relapse prevention. Acta Psychiatrica Scandinavica. Supplementum No. 382, 54–57.CrossRefGoogle ScholarPubMed
Gottesman, I.I. (1991). Schizophrenia Genesis: the Origin of Madness. Freeman: New York.Google Scholar
Harrison, P.J. & Weinberger, D.R. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Molecular Psychiatry 10, 40–68; image 45.CrossRefGoogle ScholarPubMed
Henquet, C., Krabbendam, L., Spauwen, J., Kaplan, C., Lieb, R., Wittchen, H.U. & van Os, J. (2005). Prospective cohort study of cannabis use. predisposition for psychosis, and psychotic symptoms in young people. British Medical Journal 330, 11.CrossRefGoogle ScholarPubMed
Hunter, D. J. (2005). Gene-environment interactions in human diseases. Nature Reviews. Genetics 6, 287–298.CrossRefGoogle ScholarPubMed
Jablensky, A. (2005). The long and winding road of schizophrenia research. Epidemiológia e Psichiatria Sociale 14, 179–183.CrossRefGoogle Scholar
Kapur, S. (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 160, 13–23.CrossRefGoogle ScholarPubMed
Kato, T., Iwamoto, K., Kakiuchi, C., Kuratomi, G. & Okazaki, Y. (2005). Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders. Molecular Psychiatry 10, 622–630.CrossRefGoogle ScholarPubMed
Kendler, K.S. (1997). Social support: a genetic-epidemiologic analysis. American Journal of Psychiatry 154, 1398–1404.Google ScholarPubMed
Kendler, K.S. (2005). “A gene for…”: the nature of gene action in psychiatric disorders. American Journal of Psychiatry 162, 1243–1252.CrossRefGoogle ScholarPubMed
Kennedy, J.L., Farrer, L.A., Andreasen, N.C., Mayeux, R. & St George-Hyslop, P. (2003). The genetics of adult-onset neuropsychiatrie disease: complexities and conundra? Science 302, 822–826.CrossRefGoogle Scholar
Khoury, M.J. (2000). Will genetics revolutionize medicine? New England Journal of Medicine 343, 1497.Google ScholarPubMed
Khoury, M.J., Burke, W. & Thompson, E.J. (2000). Genetics and Public Health in the 21st Century. Using Genetic Information to Improve Health and Prevent Disease. Oxford University Press: New York.CrossRefGoogle Scholar
Khoury, M.J., Davis, R., Gwinn, M., Lindegren, M.L. & Yoon, P. (2005). Do we need genomie research for the prevention of common diseases with environmental causes? American Journal of Epidemiology 161, 799–805.CrossRefGoogle Scholar
Krabbendam, L. & van Os, J. (2005). Schizophrenia and urbanicity: a major environmental influence—conditional on genetic risk. Schizophrenia Bulletin 31, 795–799.CrossRefGoogle Scholar
Kraemer, H. C., Kazdin, A.E., Offord, D.R., Kessler, R.C., Jensen, P.S. & Kupfer, D.J. (1997). Coming to terms with the terms of risk. Archives of General Psychiatry 54, 337–343.CrossRefGoogle ScholarPubMed
Kunugi, H., Nanko, S., Takei, N., Saito, K., Murray, R.M. & Hirose, T. (1996). Perinatal complications and schizophrenia. Data from the Maternal and Child Health Handbook in Japan. Journal of Nervous and Mental Disease 184, 542–546.CrossRefGoogle ScholarPubMed
Lewis, C.M., Levinson, D.F., Wise, L.H., DeLisi, L.E., Straub, R.E., Hovatta, I., Williams, N.M., Schwab, S.G., Pulver, A.E., Faraone, S.V., Brzustowicz, L.M., Kaufmann, C.A., Garver, D.L., Gurling, H.M., Lindholm, E., Coon, H., Moises, H.W., Byerley, W., Shaw, S.H., Mesen, A., Sherrington, R., O'Neill, F.A., Walsh, D., Kendler, K.S., Ekelund, J., Paunio, T., Lonnqvist, J., Peltonen, L., O'Donovan, M.C., Owen, M.J., Wildenauer, D.B., Maier, W., Nestadt, G., Blouin, J.L., Antonarakis, S.E., Mowry, B.J., Silverman, J.M., Crowe, R.R., Cloninger, C.R., Tsuang, M.T., Malaspina, D., Harkavy-Friedman, J.M., Svrakic, D.M., Bassett, A.S., Holcomb, J., Kalsi, G., McQuillin, A., Brynjolfson, J., Sigmundsson, T., Petursson, H., Jazin, E., Zoega, T. & Helgason, T. (2003). Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. American Journal of Human Genetetics 73, 34–48.CrossRefGoogle ScholarPubMed
McGrath, J. (2002). Prevention of schizophrenia - not an impossible dream. In The Epidemiology of Schizophrenia (ed. Murray, R., Jones, P., Susser, E., van Os, J. and Cannon, M.), pp. 427–439. Cambridge University Press: Cambridge.CrossRefGoogle Scholar
McGrath, J., Saha, S., Welham, J., El Saadi, O., MacCauley, C. & Chant, D. (2004). A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Medicine 2, 13.CrossRefGoogle ScholarPubMed
McGuffin, P. (2004). Nature and nurture interplay: schizophrenia. Psychiatrische Praxis 31, Suppl. 2, S189–193.CrossRefGoogle ScholarPubMed
McGuffin, P., Asherson, P., Owen, M. & Farmer, A. (1994). The strength of the genetic effect. Is there room for an environmental influence in the aetiology of schizophrenia? British Journal of Psychiatry 164, 593–599.CrossRefGoogle ScholarPubMed
McGuffin, P., Owen, M. & Gottesman, I. (2002). Psychiatic Genetics and Genomics. Oxford University Press: Oxford.CrossRefGoogle Scholar
Moffitt, T.E., Caspi, A. & Rutter, M. (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry 62, 473–481.CrossRefGoogle ScholarPubMed
Mortensen, P.B., Pedersen, C. B., Westergaard, T., Wohlfahrt, J., Ewald, H., Mors, O., Andersen, P.K. & Melbye, M. (1999). Effects of family history and place and season of birth on the risk of schizophrenia. New England Journal of Medicine 340, 603–608.CrossRefGoogle ScholarPubMed
Murray, C.L.J. & Lopez, A.D. (1996). The Global Burden of Disease. Harvard University Press: Cambridge, MA.Google ScholarPubMed
Murray, R.M. & Lewis, S.W. (1987). Is schizophrenia a neurodevelopmental disorder? British Medical Journal (Clinical Research Edition) 295, 681–682.CrossRefGoogle ScholarPubMed
Murray, R., Jones, P., Susser, E., van Os, J. & Cannon, M. (2002). The Epidemiology of Schizophrenia. Cambridge University Press: Cambridge.CrossRefGoogle Scholar
Myin-Germeys, I., van Os, J., Schwartz, J.E., Stone, A.A. & Delespaul, P.A. (2001). Emotional reactivity to daily life stress in psychosis. Archives of General Psychiatry 58, 1137–1144.CrossRefGoogle ScholarPubMed
Nimgaonkar, V.L., Wessely, S. & Murray, R.M. (1988). Prevalence of familiality, obstetric complications, and structural brain damage in schizophrenic patients. British Journal of Psychiatry 153, 191–197.CrossRefGoogle ScholarPubMed
O'Callaghan, E., Gibson, T., Colohan, H.A., Buckley, P., Walshe, D.G., Larkin, C. & Waddington, J.L. (1992). Risk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study. British Medical Journal 305, 1256–1259.CrossRefGoogle ScholarPubMed
Owen, M.J., Craddock, N. & O'Donovan, M. C. (2005). Schizophrenia: genes at last? Trends in Genetics 21, 518–525.CrossRefGoogle ScholarPubMed
Pariante, C.M., Dazzan, P., Danese, A., Morgan, K.D., Brudaglio, F., Morgan, C., Fearon, P., Orr, K., Hutchinson, G., Pantelis, C., Velakoulis, D., Jones, P.B., Leff, J. & Murray, R.M. (2005). Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the AEsop first-onset psychosis study. Neuropsychopharmacology 30, 1923–1931.CrossRefGoogle ScholarPubMed
Pedersen, C.B. & Mortensen, P.B. (2001). Evidence of a dose-response relationship between urbanicity during upbringing and schizophrenia risk. Archives of General Psychiatry 58, 1039–1046.CrossRefGoogle ScholarPubMed
Pharoah, F.M., Rathbone, J., Mari, J.J. & Streiner, D. (2003). Family intervention for schizophrenia. Cochrane Database of Systematic Reviews, Issue 3.CrossRefGoogle Scholar
Plomin, R., DeFries, J.C. & Loehlin, J.C. (1977). Genotype-environment interaction and correlation in the analysis of human behavior. Psychological Bulletin 84, 309–322.CrossRefGoogle ScholarPubMed
Plomin, R., DeFries, J.C., McClearn, G.E. & McGuffin, P. (2001). Behavioral Genetics. Worth Publishers: New York.Google Scholar
Regier, D.A., Farmer, M.E., Rae, D.S., Locke, B.Z., Keith, S.J., Judd, L.L. & Goodwin, F.K. (1990). Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologie Catchment Area (ECA) Study. Journal of the American Medical Association 264, 2511–2518.CrossRefGoogle Scholar
Reich, D.E., Cargill, M., Bolk, S., Ireland, J., Sabeti, P.C., Richter, D.J., Lavery, T., Kouyoumjian, R., Farhadian, S.F., Ward, R. & Lander, E.S. (2001). Linkage disequilibrium in the human genome. Nature 411, 199–204.CrossRefGoogle ScholarPubMed
Risch, N.J. (2000). Searching for genetic determinants in the new millennium. Nature 405, 847–856.CrossRefGoogle ScholarPubMed
Rosanoff, A.J., Handy, L.M., Plesset, I.R. & Brush, S. (1934). The etiology of so-called schizophrenic psychoses: with special reference to their occurrence in twins. American Journal of Psychiatry 91, 247–286.CrossRefGoogle Scholar
Rose, G. (1994). The Strategy of Preventive Medicine. Oxford University Press: Oxford.Google Scholar
Roses, A.D. (2000). Pharmacogenetics and the practice of medicine. Nature 405, 857–865.CrossRefGoogle ScholarPubMed
Rutter, M. & Silberg, J. (2002). Gene-environment interplay in relation to emotional and behavioral disturbance. Annual Review of Psychology 53, 463–490.CrossRefGoogle ScholarPubMed
Rutter, M., Pickles, A., Murray, R. & Eaves, L. (2001). Testing hypotheses on specific environmental causal effects on behavior. Psychological Bulletin 127, 291–324.CrossRefGoogle ScholarPubMed
Sacker, A., Done, D.J. & Crow, T.J. (1996). Obstetric complications in children born to parents with schizophrenia: a meta-analysis of case-control studies. Psychological Medicine 26, 279–287.CrossRefGoogle ScholarPubMed
Sankar, P., Cho, M. K., Condit, C. M., Hunt, L. M., Koenig, B., Marshall, P., Lee, S. S. & Spicer, P. (2004). Genetic research and health disparities. Journal of American Medical Association 291, 2985–2989.CrossRefGoogle ScholarPubMed
Scarr, S. & McCartney, K. (1983). How people make their own environments: a theory of genotype greater than environment effects. Child Development 54, 424–435.Google ScholarPubMed
Schiffman, J., Nakamura, B., Earleywine, M. & LaBrie, J. (2005). Symptoms of schizotypy precede cannabis use. Psychiatry Research 134, 37–42.CrossRefGoogle ScholarPubMed
Selten, J.P., Cantor-Graae, E., Slaets, J. & Kahn, R.S. (2002). Odegaard's selection hypothesis revisited: schizophrenia in Surinamese immigrants to The Netherlands. American Journal of Psychiatry 159, 669–671.CrossRefGoogle Scholar
Sullivan, P.F., Kendler, K.S. & Neale, M.C. (2003). Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry 60, 1187–1192.CrossRefGoogle ScholarPubMed
Tabor, H.K., Risch, N.J. & Myers, R.M. (2002). Opinion: Candidate-gene approaches for studying complex genetic traits: practical considerations. Nature Reviews. Genetics 3, 391–397.CrossRefGoogle Scholar
Taubes, G. (1995). Epidemiology faces its limits. Science 269, 164–169.CrossRefGoogle ScholarPubMed
Thompson, W.D. (1991). Effect modification and the limits of biological inference from epidemiologie data. Journal of Clinical Epidemiology 44, 221–232.CrossRefGoogle Scholar
Thornicroft, G. & Tansella, M. (1999). The Mental Health Matrix: a Manual to Improve Services. Cambridge University Press: Cambridge.CrossRefGoogle Scholar
Tienari, P., Wynne, L.C., Moring, J., Lahti, I., Naarala, M., Sorri, A., Wahlberg, K.E., Saarento, O., Seitamaa, M., Kaleva, M. & et al. (1994). The Finnish adoptive family study of schizophrenia. Implications for family research. British Journal of Psychiatry, Suppl. 23, 27–28.Google ScholarPubMed
Tsuang, M. (2000). Schizophrenia: genes and environment. Biological Psychiatry' 47, 210–220.CrossRefGoogle ScholarPubMed
van Os, J. (2004). Does the urban environment cause psychosis? British Journal of Psychiatry 184, 287–288.CrossRefGoogle ScholarPubMed
van Os, J. & Sham, P. (2002). Gene-environment correlation and interaction in schizophrenia. In The Epidemiology of Schizophrenia (ed. Murray, R., Jones, P., Susser, E., van Os, J. and Cannon, M.), pp. 235–253. Cambridge University Press: Cambridge.Google Scholar
van Os, J., Fahy, T.A., Bebbington, P., Jones, P., Wilkins, S., Sham, P., Russell, A., Gilvarry, K., Lewis, S., Toone, B. & et al. (1994). The influence of life events on the subsequent course of psychotic illness. A prospective follow-up of the Camberwell Collaborative Psychosis Study. Psychological Medicine 24, 503–513.CrossRefGoogle ScholarPubMed
van Os, J., Bak, M., Hanssen, M., Bijl, R.V., de Graaf, R. & Verdoux, H. (2002). Cannabis use and psychosis: a longitudinal population-based study. American Journal of Epidemiology 156, 319–327.CrossRefGoogle ScholarPubMed
van Os, J., Hanssen, M., Bak, M., Bijl, R.V. & Vollebergh, W. (2003). Do urbanicity and familial liability coparticipate in causing psychosis? American Journal of Psychiatry 160, 477–482.CrossRefGoogle ScholarPubMed
Vaughn, C. & Leff, J. (1976). The measurement of expressed emotion in the families of psychiatric patients. British Journal of Social and Clinical Psychology 15, 157–165.CrossRefGoogle ScholarPubMed
Verdoux, H., Gindre, C., Sorbara, F., Tournier, M. & Swendsen, J. D. (2003). Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study. Psychological Medicine 33, 23–32.CrossRefGoogle ScholarPubMed
Wahlberg, K.E., Wynne, L.C., Oja, H., Keskitalo, P., Pykalainen, L., Lahti, I., Moring, J., Naarala, M., Sorri, A., Seitamaa, M., Laksy, K., Kolassa, J. & Tienari, P. (1997). Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia. American Journal of Psychiatry 154, 355–362.Google ScholarPubMed
Willett, W.C. (2002). Balancing life-style and genomics research for disease prevention. Science 296, 695–698.CrossRefGoogle ScholarPubMed
Woo, S.M., Goldstein, M.J. & Nuechterlein, K.H. (1997). Relatives' expressed emotion and non-verbal signs of subclinical psychopathology in schizophrenic patients. British Journal of Psychiatry 170, 58–61.CrossRefGoogle ScholarPubMed