Skip to main content

Gene-Environment Interactions, Stress, and Depression

  • Living reference work entry
  • Latest version View entry history
  • First Online:
Handbook of Psychocardiology

Abstract

Depression is one of the most prevalent disorders worldwide, with high comorbidity with cardiovascular disease (CVD). Despite significant heritability, robust genetic associations are yet to be identified in depression. Multiple factors are accountable for this, including that genetic studies have not widely considered environmental factors, despite their established association with depression. One such factor is stress, a robust risk factor for depression; many genetic studies have failed to include nurture in their research into depression. The first gene-environment interaction (GxE) study in depression was published in 2003, reporting a significant interaction between a functional polymorphism in the serotonin transporter gene (5-HTTLPR) and recent stressors to predict depression. Many studies aimed to replicate this finding, as well as investigate other candidate genes (i.e., CRHR1, GR, FKBP5, BDNF). Initially, findings appeared not to reach a clear consensus; however, a closer analysis of the literature has shown that there are consistencies when specific methodological aspects are considered (i.e., timing of stressors). While there are some exciting and strongly evidenced findings, GxE research continues to face some significant challenges. This includes recognition of the importance of subtle method differences and also sample size. Samples are relatively small due to the time required to ascertain high-quality environmental data relative to standard genetic association studies, compromising power. Ascertaining large samples must therefore be made a priority in GxE research to enable further discoveries. GxE studies in depression have the potential to inform disease mechanisms that may be relevant to CVD, informing future CVD-depression research.

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

Access this chapter

Institutional subscriptions

Similar content being viewed by others

References

  • Alexander, N., Osinsky, R., Schmitz, A., Mueller, E., Kuepper, Y., & Hennig, J. (2010). The BDNF Val66Met polymorophism affects HPA-axis reactivity to acute stress. Psychoneuroendocrinology, 35(6), 949–953.

    Article  PubMed  Google Scholar 

  • Appel, K., Schwahn, C., Mahler, J., Schulz, A., Spitzer, C., Fenske, K., … Grabe, H. J. (2011). Moderation of adult depression by a polymorphism in the FKBP5 gene and childhood physical abuse in the general population. Neuropsychopharmacology, 36(10), 1982–1991. doi:10.1038/npp.2011.81.

    Google Scholar 

  • Barth, J., Schumacher, M., & Herrmann-Lingen, C. (2004). Depression as a risk factor for mortality in patients with coronary heart disease: A meta-analysis. Psychosomatic Medicine, 66(6), 802–813. doi:10.1097/01.psy.0000146332.53619.b2.

    Article  PubMed  Google Scholar 

  • Bennett, A. J., Lesch, K. P., Heils, A., Long, J. C., Lorenz, J. G., Shoaf, S. E., … Higley, J. D. (2002). Early experience and serotonin transporter gene variation interact to influence primate CNS function. Molecular Psychiatry, 7(1), 118–122. doi:10.1038/sj/mp/4000949.

    Google Scholar 

  • Bet, P. M., Penninx, B. W., Bochdanovits, Z., Uitterlinden, A. G., Beekman, A. T., van Schoor, N. M., … Hoogendijk, W. J. (2009). Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene-environment interaction. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 150B(5), 660–669. doi:10.1002/ajmg.b.30886.

    Google Scholar 

  • Binder, E. B. (2009). The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology, 34(Suppl 1), S186–S195. doi:10.1016/j.psyneuen.2009.05.021.

    Article  PubMed  Google Scholar 

  • Binder, E. B., Salyakina, D., Lichtner, P., Wochnik, G. M., Ising, M., Putz, B., … Muller-Myhsok, B. (2004). Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nature Genetics, 36(12), 1319–1325. doi:10.1038/ng1479.

    Google Scholar 

  • Binder, E. B., Bradley, R. G., Liu, W., Epstein, M. P., Deveau, T. C., Mercer, K. B., … Ressler, K. J. (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299(11), 1291–1305. doi:10.1001/jama.299.11.1291.

    Google Scholar 

  • Bondy, B. (2007). Common genetic factors for depression and cardiovascular disease. Dialogues in Clinical Neuroscience, 9(1), 19–28.

    PubMed  PubMed Central  Google Scholar 

  • Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P., Liu, W., … Ressler, K. J. (2008). Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene. Archives of General Psychiatry, 65(2), 190–200. doi:10.1001/archgenpsychiatry.2007.26.

    Google Scholar 

  • Brown, G. W., Ban, M., Craig, T. K., Harris, T. O., Herbert, J., & Uher, R. (2013). Serotonin transporter length polymorphism, childhood maltreatment, and chronic depression: A specific gene-environment interaction. Depression and Anxiety, 30(1), 5–13. doi:10.1002/da.21982.

    Article  PubMed  Google Scholar 

  • Brown, G. W., Craig, T. K., Harris, T. O., Herbert, J., Hodgson, K., Tansey, K. E., & Uher, R. (2014). Functional polymorphism in the brain-derived neurotrophic factor gene interacts with stressful life events but not childhood maltreatment in the etiology of depression. Depression and Anxiety, 31(4), 326–334. doi:10.1002/da.22221.

    Article  PubMed  Google Scholar 

  • Carvalho, L. A., Nikkheslat, N., & Pariante, C. M. (2013). Inflame-beat: Insufficient glucocorticoid signalling and inflammatory activation in coronary heart disease patients with depression. European Neuropsychopharmacology, 23((Carvalho L.A.) University College London, Epidemiology and Public Health, London, United Kingdom), S342–S343.

    Google Scholar 

  • Caspi, A., & Moffitt, T. E. (2006). Gene-environment interactions in psychiatry: Joining forces with neuroscience. Nature Review Neuroscience, 7(7), 583–590. doi:10.1038/nrn1925.

    Article  PubMed  Google Scholar 

  • Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., … Poulton, R. (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297(5582), 851–854. doi:10.1126/science.1072290.

    Google Scholar 

  • Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., … Poulton, R. (2003). Influence of life-stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301(5631), 386–389. doi:10.1126/science.1083968.

    Google Scholar 

  • Castren, E., Voikar, V., & Rantamaki, T. (2007). Role of neurotrophic factors in depression. Current Opinion in Pharmacology, 7(1), 18–21. doi:10.1016/j.coph.2006.08.009.

    Article  PubMed  Google Scholar 

  • Cicchetti, D., Rogosch, F. A., & Oshri, A. (2011). Interactive effects of corticotropin releasing hormone receptor 1, serotonin transporter linked polymorphic region, and child maltreatment on diurnal cortisol regulation and internalizing symptomatology. Development and Psychopathology, 23(Special Issue 04), 1125–1138. doi:10.1017/S0954579411000599.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cohen-Woods, S., Craig, I. W., & McGuffin, P. (2013). The current state of play on the molecular genetics of depression. Psychological Medicine, 43(4), 673–687. doi:10.1017/s0033291712001286.

    Article  PubMed  Google Scholar 

  • Collier, D. A., Stober, G., Li, T., Heils, A., Catalano, M., Di Bella, D., … Lesch, K. P. (1996). A novel functional polymorphism within the promoter of the serotonin transporter gene: Possible role in susceptibility to affective disorders. Molecular Psychiatry , 1(6), 453–460.

    Google Scholar 

  • Culverhouse, R. C., Bowes, L., Breslau, N., Nurnberger, J. I., Jr., Burmeister, M., Fergusson, D. M., … Bierut, L. J. (2013). Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression. BMC Psychiatry, 13, 304. doi:10.1186/1471-244x-13-304.

    Google Scholar 

  • Dackis, M. N., Rogosch, F. A., Oshri, A., & Cicchetti, D. (2012). The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: Moderation by FK506 binding protein 5 haplotype. Development and Psychopathology, 24(4), 1237–1252. doi:10.1017/s0954579412000673.

    Article  PubMed  PubMed Central  Google Scholar 

  • Danese, A., Moffitt, T. E., Pariante, C. M., Ambler, A., Poulton, R., & Caspi, A. (2008). Elevated inflammation levels in depressed adults with a history of childhood maltreatment. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Archives of General Psychiatry, 65(4), 409–415. doi:10.1001/archpsyc.65.4.409.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dannlowski, U., Ohrmann, P., Bauer, J., Kugel, H., Arolt, V., Heindel, W., … Suslow, T. (2007). Amygdala reactivity to masked negative faces is associated with automatic judgmental bias in major depression: A 3 T fMRI study. Journal of Psychiatry & Neuroscience, 32(6), 423–429.

    Google Scholar 

  • de Kloet, E. R., Joels, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Review Neuroscience, 6(6), 463–475. doi:10.1038/nrn1683.

    Article  Google Scholar 

  • Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. The American Journal of Psychiatry, 168(10), 1041–1049. doi:10.1176/appi.ajp.2011.11020191.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dunn, E. C., McLaughlin, K. A., Slopen, N., Rosand, J., & Smoller, J. W. (2013). Genetic variants modify the association between developmental timing of exposure to physical and sexual abuse and depressive symptoms in young adulthood: Evidence of a sensitive period?. Depression and Anxiety, 54, e20–e20.

    Google Scholar 

  • Eley, T. C., Sugden, K., Corsico, A., Gregory, A. M., Sham, P., McGuffin, P., … Craig, I. W. (2004). Gene-environment interaction analysis of serotonin system markers with adolescent depression. Molecular Psychiatry, 9(10), 908–915. doi:10.1038/sj.mp.4001546.

    Google Scholar 

  • Furlong, R. A., Ho, L., Walsh, C., Rubinsztein, J. S., Jain, S., Paykel, E. S., … Rubinsztein, D. C. (1998). Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders. [Meta-Analysis Research Support, Non-U.S. Gov’t]. American Journal of Medical Genetics, 81(1), 58–63. [Research Support, Non-U.S. Gov’t]. Molecular Psychiatry, 14(7), 681–695. doi:10.1038/mp.2008.143.

    Google Scholar 

  • Gilman, S. E., Kawachi, I., Fitzmaurice, G. M., & Buka, L. (2003). Socio-economic status, family disruption and residential stability in childhood: Relation to onset, recurrence and remission of major depression. Psychological Medicine, 33(8), 1341–1355.

    Article  PubMed  Google Scholar 

  • Grabe, H. J., Schwahn, C., Appel, K., Mahler, J., Schulz, A., Spitzer, C., … Volzke, H. (2010). Childhood maltreatment, the corticotropin-releasing hormone receptor gene and adult depression in the general population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153B(8), 1483–1493. doi:10.1002/ajmg.b.31131.

    Google Scholar 

  • Hauser, J., LeszczyÅ„ska, A., Samochowiec, J., Czerski, P. M., Ostapowicz, A., Chlopocka, M., & Rybakowski, J. K. (2003). Association analysis of the insertion/deletion polymorphism in serotonin transporter gene in patients with affective disorder. European Psychiatry, 18(3), 129–132. doi:10.1016/s0924-9338(03)00026-9.

    Article  PubMed  Google Scholar 

  • Hedges, L. V., & Olkin, I. (1985). Statistical methods for meta-analysis. Orlando: Academic.

    Google Scholar 

  • Holsboer, F. (2000). The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology, 23(5), 477–501. doi:10.1016/s0893-133x(00)00159-7.

    Article  PubMed  Google Scholar 

  • Hosang, G. M., Shiles, C., Tansey, K. E., McGuffin, P., & Uher, R. (2014). Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis. BMC Medicine, 12, 7. doi:10.1186/1741-7015-12-7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Isometsa, E. (2014). Suicidal behaviour in mood disorders – Who, when, and why? Canadian Journal of Psychiatry, 59(3), 120–130. [Research Support, N.I.H., Extramural]. Journal of Psychiatric Research, 47(2), 233–239. doi:10.1016/j.jpsychires.2012.10.009.

    PubMed  PubMed Central  Google Scholar 

  • Kalueff, A. V., Avgustinovich, D. F., Kudryavtseva, N. N., & Murphy, D. L. (2006). BDNF in anxiety and depression. Science, 312(5780), 1598–1599. doi:10.1126/science.312.5780.1598; author reply 1598–1599.

    Article  PubMed  Google Scholar 

  • Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68(5), 444–454. doi:10.1001/archgenpsychiatry.2010.189.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999). Causal relationship between stressful life events and the onset of major depression. The American Journal of Psychiatry, 156(6), 837–841.

    Article  PubMed  Google Scholar 

  • Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., … Kendler, K. S. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Co-morbidity Survey. Archives of General Psychiatry, 51(1), 8–19.

    Google Scholar 

  • Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., & Moffitt, T. E. (2006). MAOA, maltreatment, and gene-environment interaction predicting children’s mental health: New evidence and a meta-analysis. Molecular Psychiatry, 11(10), 903–913. doi:10.1038/sj.mp.4001851.

    Article  PubMed  Google Scholar 

  • Kranzler, H. R., Feinn, R., Nelson, E. C., Covault, J., Anton, R. F., Farrer, L., & Gelernter, J. (2011). A CRHR1 haplotype moderates the effect of adverse childhood experiences on lifetime risk of major depressive episode in African-American women. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 156(8), 960–968. doi:10.1002/ajmg.b.31243.

    Article  PubMed Central  Google Scholar 

  • Kunugi, H., Ida, I., Owashi, T., Kimura, M., Inoue, Y., Nakagawa, S., … Mikuni, M. (2006). Assessment of the dexamethasone/CRH test as a state-dependent marker for hypothalamic-pituitary-adrenal (HPA) axis abnormalities in major depressive episode: A multicenter study. Neuropsychopharmacology, 31(1), 212–220. doi:10.1038/sj.npp.1300868.

    Google Scholar 

  • Kunugi, H., Hori, H., Adachi, N., & Numakawa, T. (2010). Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression. Psychiatry and Clinical Neurosciences, 64(5), 447–459. doi:10.1111/j.1440-1819.2010.02135.x.

    Article  PubMed  Google Scholar 

  • Ladd, C. O., Huot, R. L., Thrivikraman, K. V., Nemeroff, C. B., Meaney, M. J., & Plotsky, P. M. (2000). Long-term behavioral and neuroedocrine adaptations to adverse early experience. Progress in Brain Research, 122, 81–103.

    Article  PubMed  Google Scholar 

  • Lepine, J. P., & Briley, M. (2011). The increasing burden of depression. Neuropsychiatric Disease and Treatment, 7(Suppl 1), 3–7. doi:10.2147/ndt.s19617.

    PubMed  PubMed Central  Google Scholar 

  • Lerer, B., Macciardi, F., Segman, R. H., Adolfsson, R., Blackwood, D., Blairy, S., … Mendlewicz, J. (2001). Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder. Molecular Psychiatry, 6(5), 579–585. doi:10.1038/sj.mp.4000883.

    Google Scholar 

  • Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., … Murphy, D. L. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274(5292), 1527–1531.

    Google Scholar 

  • Lesperance, F., Frasure-Smith, N., Talajic, M., & Bourassa, M. G. (2002). Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction. Circulation, 105(9), 1049–1053.

    Article  PubMed  Google Scholar 

  • Liu, Z., Liu, W., Yao, L., Yang, C., Xiao, L., Wan, Q., … Xiao, Z. (2013). Negative life events and corticotropin-releasing-hormone receptor1 gene in recurrent major depressive disorder. Scientific Reports, 3. doi:10.1038/srep01548.

    Google Scholar 

  • Ma, J., Yu, S. Y., Liang, S., Ding, J., Feng, Z., Yang, F., … Su, L. Y. (2013). [Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents]. Zhongguo Dang Dai Er Ke Za Zhi, 15(7), 563–568.

    Google Scholar 

  • Mandelli, L., Emiliani, R., Porcelli, S., Fabbri, C., Albani, D., & Serretti, A. (2014). Genes involved in neuroplasticity and stressful life events act on the short-term response to antidepressant treatment: A complex interplay between genetics and environment. Human Psychopharmacology, 29(4), 388–391. doi:10.1002/hup.2411.

    Article  PubMed  Google Scholar 

  • McAuley, E. Z., Scimone, A., Tiwari, Y., Agahi, G., Mowry, B. J., Holliday, E. G., … Fullerton, J. M. (2012). Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26. PLoS One, 7(5), e38172. doi:10.1371/journal.pone.0038172.

    Google Scholar 

  • McCaffery, J. M., Frasure-Smith, N., Dubé, M.-P., Théroux, P., Rouleau, G. A., Duan, Q., & Lespérance, F. (2006). Common genetic vulnerability to depressive symptoms and coronary artery disease: A review and development of candidate genes related to inflammation and serotonin. Psychosomatic Medicine, 68(2), 187–200. 110.1097/1001.psy.0000208630.0000279271.a0000208630.

    Article  PubMed  Google Scholar 

  • McEwen, B. S. (2007). Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiological Reviews, 87(3), 873–904. doi:10.1152/physrev.00041.2006.

    Article  PubMed  Google Scholar 

  • McGuffin, P., Katz, R., Watkins, S., & Rutherford, J. (1996). A hospital-based twin register of the heritability of DSM-IV unipolar depression. Archives of General Psychiatry, 53(2), 129–136.

    Article  PubMed  Google Scholar 

  • Meaney, M. J., & Szyf, M. (2005). Environmental programming of stress responses through DNA methylation: Life at the interface between a dynamic environment and a fixed genome. Dialogues in Clinical Neuroscience, 7(2), 103–123.

    PubMed  PubMed Central  Google Scholar 

  • Moffitt, T. E., & Caspi, A. (2014). Bias in a protocol for a meta-analysis of 5-HTTLPR, stress, and depression. BMC Psychiatry, 14, 179. doi:10.1186/1471-244x-14-179.

    Article  PubMed  PubMed Central  Google Scholar 

  • Munafo, M. R., Brown, S. M., & Hariri, A. R. (2008). Serotonin transporter (5-HTTLPR) genotype and amygdala activation: A meta-analysis. Biological Psychiatry, 63(9), 852–857. doi:10.1016/j.biopsych.2007.08.016.

    Article  PubMed  PubMed Central  Google Scholar 

  • Myin-Germeys, I., Peeters, F., Havermans, R., Nicolson, N. A., DeVries, M. W., Delespaul, P., & Van Os, J. (2003). Emotional reactivity to daily life-stress in psychosis and affective disorder: An experience sampling study. Acta Psychiatrica Scandinavica, 107(2), 124–131.

    Article  PubMed  Google Scholar 

  • Pagliaccio, D., Luby, J. L., Bogdan, R., Agrawal, A., Gaffrey, M. S., Belden, A. C., … Barch, D. M. (2014). Stress-system genes and life-stress predict cortisol levels and amygdala and hippocampal volumes in children. Neuropsychopharmacology, 39(5), 1245–1253. doi:10.1038/npp.2013.327.

    Google Scholar 

  • Pennebaker, J. W., & Susman, J. R. (1988). Disclosure of traumas and psychosomatic processes. Social Science and Medicine, 26(3), 327–332.

    Article  PubMed  Google Scholar 

  • Polanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A., Sugden, K., … Moffitt, T. E. (2009). Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: Replication and extension. Archives of General Psychiatry, 66(9), 978–985. doi:10.1001/archgenpsychiatry.2009.114.

    Google Scholar 

  • Risch, N., Herrell, R., Lehner, T., Liang, K. Y., Eaves, L., Hoh, J., … Merikangas, K. R. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. JAMA, 301(23), 2462–2471. doi:10.1001/jama.2009.878.

    Google Scholar 

  • Rosengren, A., Hawken, S., Ounpuu, S., Sliwa, K., Zubaid, M., Almahmeed, W. A., … Yusuf, S. (2004). Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): Case-control study. Lancet, 364(9438), 953–962. doi:10.1016/s0140-6736(04)17019-0.

    Google Scholar 

  • Rothman, K. J., & Greenland, S. (2005). Causation and causal inference in epidemiology. American Journal of Public Health, 95(Suppl 1), S144–S150. doi:10.2105/ajph.2004.059204.

    Article  PubMed  Google Scholar 

  • Roy, A., Gorodetsky, E., Yuan, Q., Goldman, D., & Enoch, M. A. (2010). Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology, 35(8), 1674–1683. doi:10.1038/npp.2009.236.

    PubMed  PubMed Central  Google Scholar 

  • Rutter, M., Moffitt, T. E., & Caspi, A. (2006). Gene-environment interplay and psychopathology: Multiple varieties but real effects. The Journal of Child Psychology and Psychiatry, 47(3-4), 226–261. doi:10.1111/j.1469-7610.2005.01557.x.

    Article  PubMed  Google Scholar 

  • Schmidt, H. D., & Duman, R. S. (2010). Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology, 35(12), 2378–2391. doi:10.1038/npp.2010.114.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sullivan, P. F., Neale, M. C., & Kendler, K.S. (2000). Genetic epidemiology of major depression: review and meta-analysis. American Journal of Psychiatry, 157(10), 1552–62.

    Google Scholar 

  • Tyrka, A. R., Price, L. H., Gelernter, J., Schepker, C., Anderson, G. M., & Carpenter, L. L. (2009). Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: Effects on hypothalamic-pituitary-adrenal axis reactivity. Biological Psychiatry, 66(7), 681–685. doi:10.1016/j.biopsych.2009.05.012.

    Article  PubMed  PubMed Central  Google Scholar 

  • Uher, R. (2014). Gene-environment interactions in severe mental illness. Front Psychiatry, 5, 48. doi:10.3389/fpsyt.2014.00048.

    Article  PubMed  PubMed Central  Google Scholar 

  • Uher, R., & McGuffin, P. (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry, 15(1), 18–22. doi:10.1038/mp.2009.123.

    Article  PubMed  Google Scholar 

  • Uher, R., Caspi, A., Houts, R., Sugden, K., Williams, B., Poulton, R., & Moffitt, T. E. (2011). Serotonin transporter gene moderates childhood maltreatment’s effects on persistent but not single-episode depression: Replications and implications for resolving inconsistent results. Journal of Affective Disorders, 135(1-3), 56–65. doi:10.1016/j.jad.2011.03.010.

    Article  PubMed  PubMed Central  Google Scholar 

  • van Oostrom, I., Franke, B., Rijpkema, M., Gerritsen, L., Arias-Vasquez, A., Fernandez, G., & Tendolkar, I. (2012). Interaction between BDNF Val66Met and childhood stressful life events is associated to affective memory bias in men but not women. Biological Psychology, 89(1), 214–219. doi:10.1016/j.biopsycho.2011.10.012.

    Article  PubMed  Google Scholar 

  • Vigushin, D. M., & Coombes, R. C. (2004). Targeted histone deacetylase inhibition for cancer therapy. Current Cancer Drug Targets, 4(2), 205–218.

    Article  PubMed  Google Scholar 

  • Weaver, I. C., Cervoni, N., Champagne, F. A., D’Alessio, A. C., Sharma, S., Seckl, J. R., … Meaney, M. J. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7(8), 847–854. doi: 10.1038/nn1276. http://www.nature.com/neuro/journal/v7/n8/suppinfo/nn1276_S1.html

    Google Scholar 

  • White, M. G., Bogdan, R., Fisher, P. M., Muñoz, K. E., Williamson, D. E., & Hariri, A. R. (2012). FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity. Genes, Brain, and Behavior, 11(7), 869–878. doi:10.1111/j.1601-183X.2012.00837.x.

    Article  PubMed  Google Scholar 

  • Wichers, M., Kenis, G., Jacobs, N., Myin-Germeys, I., Schruers, K., Mengelers, R., … van Os, J. (2008). The psychology of psychiatric genetics: Evidence that positive emotions in females moderate genetic sensitivity to social stress associated with the BDNF Val66Met polymorphism. Journal of Abnormal Psychology, 117(3), 699–704. doi:10.1037/a0012909.

    Google Scholar 

  • Widom, C. S., DuMont, K., & Czaja, S. J. (2007). A prospective investigation of major depressive disorder and co-morbidity in abused and neglected children grown up. Archives of General Psychiatry, 64(1), 49–56. doi:10.1001/archpsyc.64.1.49.

    Article  PubMed  Google Scholar 

  • World Health Organization, W. (2008). The global burden of disease 2004. Retrieved 14 Sept 2014.

    Google Scholar 

  • Wray, N. R., Purcell, S. M., & Visscher, P. M. (2011). Synthetic associations created by rare variants do not explain most GWAS results. PLoS Biology, 9(1), e1000579. doi:10.1371/journal.pbio.1000579.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xie, P., Kranzler, H. R., Poling, J., Stein, M. B., Anton, R. F., Farrer, L. A., & Gelernter, J. (2010). Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology, 35(8), 1684–1692. doi:10.1038/npp.2010.37.

    PubMed  PubMed Central  Google Scholar 

  • Yoshikawa, H., Aber, J. L., & Beardslee, W. R. (2012). The effects of poverty on the mental, emotional, and behavioral health of children and youth: Implications for prevention. The American Psychologist, 67(4), 272–284. doi:10.1037/a0028015.

    Article  PubMed  Google Scholar 

  • Yusuf, S., Hawken, S., Ounpuu, S., Dans, T., Avezum, A., Lanas, F., … Lisheng, L. (2004). Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet, 364(9438), 937–952. doi:10.1016/s0140-6736(04)17018-9.

    Google Scholar 

  • Zannas, A. S., Binder, E. B. (2014). Gene-environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. Genes Brain and Behaviour, 13(1), 25–37.

    Article  Google Scholar 

  • Zimmermann, P., Bruckl, T., Nocon, A., Pfister, H., Binder, E. B., Uhr, M., … Ising, M. (2011). Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: Results from a 10-year prospective community study. The American Journal of Psychiatry, 168(10), 1107–1116. doi:10.1176/appi.ajp.2011.10111577.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sarah Cohen-Woods .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 © Her Majesty the Queen in Right of Australia

About this entry

Cite this entry

Cohen-Woods, S., Harkess, K.N. (2016). Gene-Environment Interactions, Stress, and Depression. In: Alvarenga, M., Byrne, D. (eds) Handbook of Psychocardiology. Springer, Singapore. https://doi.org/10.1007/978-981-4560-53-5_41-2

Download citation

  • DOI: https://doi.org/10.1007/978-981-4560-53-5_41-2

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Singapore

  • Online ISBN: 978-981-4560-53-5

  • eBook Packages: Springer Reference Behavioral Science and PsychologyReference Module Humanities and Social SciencesReference Module Business, Economics and Social Sciences

Publish with us

Policies and ethics

Chapter history

  1. Latest

    Gene-Environment Interactions, Stress, and Depression
    Published:
    24 February 2016

    DOI: https://doi.org/10.1007/978-981-4560-53-5_41-2

  2. Original

    Gene-Environment Interactions, Stress, and Depression
    Published:
    23 December 2015

    DOI: https://doi.org/10.1007/978-981-4560-53-5_41-1