Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-26T16:59:54.798Z Has data issue: false hasContentIssue false

5 - Genes and the social environment

from Part I - Theoretical and conceptual foundations

Published online by Cambridge University Press:  07 December 2009

By
Jennifer H. Barnett  and
Peter B. Jones
Edited by
Craig Morgan ,
Kwame McKenzie  and
Paul Fearon
Jennifer H. Barnett
Affiliation:
Department of Psychiatry, University of Cambridge, Box 189, Addenbrooke's Hospital, Cambridge, UK
Peter B. Jones
Affiliation:
Department of Psychiatry, University of Cambridge, Box 189, Addenbrooke's Hospital, Cambridge, UK
Craig Morgan
Affiliation:
Institute of Psychiatry, King's College London
Kwame McKenzie
Affiliation:
University College London
Paul Fearon
Affiliation:
Trinity College, Dublin
Get access

Summary

Introduction

Understanding the contributions of both genes and environments is essential to unravelling the aetiology of psychosis. In this chapter, we consider how genes might interact with aspects of the social environment in the genesis of psychiatric disorders. We describe evidence for such interactions from early adoption studies to recent investigations using modern molecular genetic techniques. We discuss the principal methodological issues of such research, and the need for clarification of the mechanisms of gene–environment interaction. Finally we consider the challenges that increasing knowledge of epigenetics will bring to the field.

History and overview of the field

Schizophrenia and other psychotic illnesses are undoubtedly highly heritable. For schizophrenia, the risk of the disorder in first-degree relatives is perhaps 5%, compared with 0.5% for the relatives of controls (Kendler and Diehl, 1993). Concordance rates for schizophrenia are 42–50% in monozygotic (identical) twins and 0–14% in dizygotic (fraternal) twins (Cardno and Murray, 2003); heritability estimates for most psychotic disorders hover around 80–85% (Cardno et al., 1999). Since concordance in monozygotic twins is not 100%, genes cannot be ‘sufficient’ causes for psychosis, though they may be ‘necessary’, and unaffected relatives may pass on an increased risk for disorder (Gottesman and Bertelsen, 1989). This high heritability does not rule out the importance of environments in the aetiology of psychosis, nor of gene–environment interactions; in fact, gene–environment interactions contribute to the heritability estimates produced by quantitative genetic studies (Moffitt et al., 2005).

Keywords

Dunedin birth cohortenvironmental riskgene-environment interactionsmodern molecular genetic techniquespsychiatric disordersschizophrenia
Type
Chapter
Information
Society and Psychosis , pp. 58 - 74
Publisher: Cambridge University Press
Print publication year: 2008

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

Andreasson, S., Allebeck, P., Engstrom, A.et al. (1987). Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet, 2, 1483–6.Google Scholar
Arseneault, L., Cannon, M., Witton, J.et al. (2004). Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry, 184, 110–17.Google Scholar
Barnett, J. H., Heron, J., Ring, S. M.et al. (2007). Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children. American Journal of Psychiatry, 164, 142–9.Google Scholar
Boer, H., Holland, A., Whittington, J.et al. (2002). Psychotic illness in people with Prader–Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet, 359, 135–6.Google Scholar
Brunner, H. G., Nelen, M., Breakefield, X. O.et al. (1993). Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science, 262, 578–80.Google Scholar
Caldji, C., Tannenbaum, B., Sharma, S.et al. (1998). Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proceedings of the National Academy of Sciences of the USA, 95, 5335–40.Google Scholar
Cannon, T. D., Erp, T. G., Rosso, I. M.et al. (2002). Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls. Archives of General Psychiatry, 59, 35–41.Google Scholar
Cardno, A. and Murray, R. M. (2003). The ‘classical’ genetic epidemiology of schizophrenia. In The Epidemiology of Schizophrenia, ed. Murray, R. M., Jones, P. B., Susser, E., Os, J. and Cannon, M.. Cambridge: Cambridge University Press, pp. 194–219.
Cardno, A. G., Marshall, E. J., Coid, B.et al. (1999). Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Archives of General Psychiatry, 56, 162–8.Google Scholar
Carlson, J. (1999). Inborn resistance to malaria. In Malaria: Molecular and Clinical Aspects, ed. Wahlgren, M. and Perlmann, P.. Amsterdam: Harwood Academic Publishers, pp. 363–78.
Cases, O., Seif, I., Grimsby, J.et al. (1995). Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science, 268, 1763–6.Google Scholar
Caspi, A., McClay, J., Moffitt, T. E.et al. (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297, 851–4.Google Scholar
Caspi, A., Sugden, K., Moffitt, T. E.et al. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science, 301, 386–9.Google Scholar
Caspi, A., Moffitt, T. E., Cannon, M.et al. (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, 1117–27.Google Scholar
Clarke, M. C., Harley, M. and Cannon, M. (2006). The role of obstetric events in schizophrenia. Schizophrenia Bulletin, 32, 3–8.Google Scholar
Clayton, D. and McKeigue, P. M. (2001). Epidemiological methods for studying genes and environmental factors in complex diseases. Lancet, 358, 1356–60.Google Scholar
Luca, C. R., Wood, S. J., Anderson, V.et al. (2003). Normative data from the CANTAB. I: development of executive function over the lifespan. Journal of Clinical and Experimental Neuropsychology, 25, 242–54.Google Scholar
Egan, M. F., Goldberg, T. E., Kolachana, B. S.et al. (2001). Effect of COMT Val108/158Met genotype on frontal lobe function and risk for schizophrenia. Proceedings of the National Academy of Sciences of the USA, 98, 6917–22.Google Scholar
El-Saadi, O., Pedersen, C. B., McNeil, T. F.et al. (2004). Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia. Schizophrenia Research, 67, 227–36.Google Scholar
Fan, J. B., Zhang, C. S., Gu, N. F.et al. (2005). Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biological Psychiatry, 57, 139–44.Google Scholar
Foley, D. L., Eaves, L. J., Wormley, B.et al. (2004). Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Archives of General Psychiatry, 61, 738–44.Google Scholar
Francis, D., Diorio, J., Liu, D.et al. (1999). Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science, 286, 1155–8.Google Scholar
Giedd, J. N. (2004). Structural magnetic resonance imaging of the adolescent brain. Annals of the New York Academy of Sciences, 1021, 77–85.Google Scholar
Gillespie, N. A., Whitfield, J. B., Williams, B.et al. (2005). The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychological Medicine, 35, 101–11.Google Scholar
Gogos, J. A., Morgan, M., Luine, V.et al. (1998). Catechol-O-methyltransferase deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proceedings of the National Academy of Sciences of the USA, 95, 9991–6.Google Scholar
Golding, J., Pembrey, M. and Jones, R. (2001). ALSPAC – the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatric and Perinatal Epidemiology, 15, 74–87.Google Scholar
Gottesman, I. I. and Bertelsen, A. (1989). Confirming unexpressed genotypes for schizophrenia. Risks in the offspring of Fischer's Danish identical and fraternal discordant twins. Archives of General Psychiatry, 46, 867–72.Google Scholar
Hafner, H., Maurer, K., Trendler, G.et al. (2005). Schizophrenia and depression: challenging the paradigm of two separate diseases – a controlled study of schizophrenia, depression and healthy controls. Schizophrenia Research, 77, 11–24.Google Scholar
Harrison, P. J. and Weinberger, D. R. (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Molecular Psychiatry, 10, 804.Google Scholar
Henquet, C., Rosa, A., Krabbendam, L.et al. (2006). An experimental study of catechol-O-methyltransferase Val158Met moderation of Δ-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology, 31, 2748–57.Google Scholar
Heston, L. L. (1966). Psychiatric disorders in foster home reared children of schizophrenic mothers. British Journal of Psychiatry, 112, 819–25.Google Scholar
Hu, X. Z., Lipsky, R. H., Zhu, G.et al. (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics, 78, 815–26.Google Scholar
Ioannidis, J. P., Ntzani, E. E., Trikalinos, T. A.et al. (2001). Replication validity of genetic association studies. Nature Genetics, 29, 306–9.Google Scholar
Jones, P., Rodgers, B., Murray, R.et al. (1994). Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet, 344, 1398–402.Google Scholar
Kaufman, J., Yang, B. Z., Douglas-Palumberi, H.et al. (2004). Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings of the National Academy of Sciences of the USA, 101, 17316–21.Google Scholar
Kaufman, J., Yang, B. Z., Douglas-Palumberi, H.et al. (2006). Brain-derived neurotrophic factor–5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry, 59, 673–80.Google Scholar
Kendler, K. S. and Diehl, S. R. (1993). The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophrenia Bulletin, 19, 261–85.Google Scholar
Kendler, K. S. and Eaves, L. J. (1986). Models for the joint effect of genotype and environment on liability to psychiatric illness. American Journal of Psychiatry, 143, 279–89.Google Scholar
Kendler, K. S. and Prescott, C. A. (1998). Cannabis use, abuse, and dependence in a population-based sample of female twins. American Journal of Psychiatry, 155, 1016–22.Google Scholar
Kendler, K. S., Neale, M., Kessler, R.et al. (1993). A twin study of recent life events and difficulties. Archives of General Psychiatry, 50, 789–96.Google Scholar
Kety, S. S., Rosenthal, D., Wender, P. H.et al. (1971). Mental illness in the biological and adoptive families of adopted schizophrenics. American Journal of Psychiatry, 128, 302–6.Google Scholar
Keverne, E. B., Fundele, R., Narasimha, M.et al. (1996). Genomic imprinting and the differential roles of parental genomes in brain development. Developmental Brain Research, 92, 91–100.Google Scholar
Krabbendam, L. and Os, J. (2005). Schizophrenia and urbanicity: a major environmental influence – conditional on genetic risk. Schizophrenia Bulletin, 31, 795–9.Google Scholar
Kurtz, M. M. (2005). Neurocognitive impairment across the lifespan in schizophrenia: an update. Schizophrenia Research, 74, 15–26.Google Scholar
Lautenschlager, N. T. and Almeida, O. P. (2006). Physical activity and cognition in old age. Current Opinion in Psychiatry, 19, 190–3.Google Scholar
Liu, D., Diorio, J., Tannenbaum, B.et al. (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science, 277, 1659–62.Google Scholar
Malaspina, D. (2001). Paternal factors and schizophrenia risk: de novo mutations and imprinting. Schizophrenia Bulletin, 27, 379–93.Google Scholar
Malaspina, D., Goetz, R. R., Friedman, J. H.et al. (2001). Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar disorder pedigrees. American Journal of Psychiatry, 158, 440–6.Google Scholar
Marcelis, M., Os, J., Sham, P.et al. (1998). Obstetric complications and familial morbid risk of psychiatric disorders. American Journal of Medical Genetics, 81, 29–36.Google Scholar
McCreadie, R. G. (2002). Use of drugs, alcohol and tobacco by people with schizophrenia: case-control study. British Journal of Psychiatry, 181, 321–5.Google Scholar
Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 1161–92.Google Scholar
Moffitt, T. E., Caspi, A. and Rutter, M. (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry, 62 (5), 473–81.Google Scholar
Owen, M. J., Williams, N. M. and O'Donovan, M. C. (2004). The molecular genetics of schizophrenia: new findings promise new insights. Molecular Psychiatry, 9, 14–27.Google Scholar
Owen, M. J., Craddock, N. and O'Donovan, M. C. (2005). Schizophrenia: genes at last? Trends in Genetics, 21, 518–25.Google Scholar
Petronis, A. (2004). The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis. Biological Psychiatry, 55, 965–70.Google Scholar
Plomin, R., DeFries, J. C., McClearn, G. E.et al. (1997). Behavioral Genetics, 3rd edn. New York: Freeman.
Regier, D. A., Farmer, M. E., Rae, D. S.et al. (1990). Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. Journal of the American Medical Association, 264, 2511–18.Google Scholar
Robinson, W. P., Bottani, A., Xie, Y. G.et al. (1991). Molecular, cytogenetic, and clinical investigations of Prader–Willi syndrome patients. American Journal of Human Genetics, 49, 1219–34.Google Scholar
Roiser, J. P., Cook, L. J., Cooper, J. D.et al. (2005). Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in Ecstasy users. American Journal of Psychiatry, 162, 609–12.Google Scholar
Rutter, M. and Silberg, J. (2002). Gene–environment interplay in relation to emotional and behavioral disturbance. Annual Review of Psychology, 53, 463–90.Google Scholar
Shanahan, M. J. and Hofer, S. M. (2005). Social context in gene–environment interactions: retrospect and prospect. Journal of Gerontology Series B – Psychological Sciences and Social Sciences, 60, 65–76.Google Scholar
Sjoberg, R. L., Nilsson, K. W., Nordquist, N.et al. (2006). Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene. International Journal of Neuropsychopharmacology, 9, 443–9.Google Scholar
Smith, J. C., Webb, T., Pembrey, M. E.et al. (1992). Maternal origin of deletion 15q11–13 in 25/25 cases of Angelman syndrome. Human Genetics, 88, 376–8.Google Scholar
Sowell, E. R., Thompson, P. M., Holmes, C. J.et al. (1999). In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience, 2, 859–61.Google Scholar
Surtees, P. G., Wainwright, N. W., Willis-Owen, S. A.et al. (2006). Social adversity, the sero-tonin transporter (5-HTTLPR) polymorphism and major depressive disorder. Biological Psychiatry, 59, 2241–9.Google Scholar
Tienari, P., Wynne, L. C., Sorri, A.et al. (2004). Genotype–environment interaction in schizophrenia-spectrum disorder. British Journal of Psychiatry, 184, 216–22.Google Scholar
Tsuang, M. T., Lyons, M. J., Eisen, S. A.et al. (1996). Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs. American Journal of Medical Genetics, 67, 473–7.Google Scholar
Os, J., Hanssen, M., Bak, M.et al. (2003). Do urbanicity and familial liability coparticipate in causing psychosis? American Journal of Psychiatry, 160, 477–82.Google Scholar
Wahlberg, K-E., Wynne, L. C., Oja, H.et al. (1997). Gene–environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia. American Journal of Psychiatry, 154, 355–62.Google Scholar
Weaver, I. C., Cervoni, N., Champagne, F. A.et al. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847–54.Google Scholar
Weinberger, D. R. (1987). Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry, 44, 660–9.Google Scholar
Wilhelm, K., Mitchell, P. B., Niven, H.et al. (2006). Life events, first depression onset and the serotonin transporter gene. British Journal of Psychiatry, 188, 210–15.Google Scholar
Zalsman, G., Huang, Y. Y., Oquendo, M. A.et al. (2006). Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression. American Journal of Psychiatry, 163, 1588–93.Google Scholar
Zammit, S. and Owen, M. J. (2006). Stressful life events, 5-HTT genotype and risk of depression. British Journal of Psychiatry, 188, 199–201.Google Scholar
Zammit, S., Allebeck, P., Dalman, C.et al. (2003). Paternal age and risk for schizophrenia. British Journal of Psychiatry, 183, 405–8.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×