The role of genetic and epigenetic factors in modulating the influence of early adverse experiences on development

Publication type Article
Status Published
Occupation: Researcher, Laboratory of Translational Sciences of Human Development
Affiliation: Saint-Petersburg State University, University of Houston, Texas Institute for Measurement, Evaluation, and Statistics
Address: Russian Federation, Saint-Petersburg, Houston
Occupation: Junior researcher, Laboratory of Translational Sciences of Human Development
Affiliation: Saint-Petersburg State University, University of Houston, Texas Institute for Measurement, Evaluation, and Statistics
Address: Russian Federation, Saint-Petersburg, Houston
Occupation: Senior Researcher, Laboratory of Human Genetics, Vavilov Institute of General Genetics RAS
Affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, University of Houston, Texas Institute for Measurement, Evaluation, and Statistics
Address: Russian Federation, Moscow, Houston
Occupation: Leading scientist of the Laboratory of Translational Sciences of Human Development
Affiliation: Saint-Petersburg State University, University of Houston, Texas Institute for Measurement, Evaluation, and Statistics
Address: Russian Federation, Saint-Petersburg, Houston
Journal namePsikhologicheskii zhurnal
EditionVolume 40 issue 5

The developmental outcome of early-life adverse experiences is considered with respect to the interaction between genetic and epigenetic factors. The mechanisms modulating the genome’s responses to environmental signals are illustrated by the discussion of the two genes that play a role in the neurohumoral response to stress, namely the serotonin transporter gene SLC6A4 and the glucocorticoid receptor gene NR3C1. Epigenetic mechanisms are considered as a modulator of these responses providing long-term changes in the phenotype. The reviewed literature highlights the need to combine information on the genome’s structure and its epigenetic status in the analysis of the impact of early-life adverse experience on subsequent development. Such combinatory analyses will also be beneficial for the purposes of personalized diagnosis and therapy of mental disorders.

KeywordsEpigenetic modifications of the genome, genetic polymorphisms, early-life experience, stress response, phenotype development.
AcknowledgmentPreparation of this article was carried out within the megagrant of the Government of the Russian Federation № 14.Z50.31.0027 “Influence of early deprivation on bio-behavioral indicators of child development”.
Publication date04.09.2019
Number of characters24224
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1. Alexander N., Wankerl M., Hennig J., Miller R., Zänkert S., Steudte-Schmiedgen S., Stalder T., Kirschbaum C. DNA methylation profiles within the serotonin transporter gene moderate the association of 5-HTTLPR and cortisol stress reactivity // Translational Psychiatry. 2014. V. 4. № 9. P. e443.

2. Bakermans-Kranenburg M.J., Dobrova-Krol N., Van IJzendoorn M. Impact of institutional care on attachment disorganization and insecurity of Ukrainian preschoolers: Protective effect of the long variant of the serotonin transporter gene (5HTT) // International Journ. of Behavioral Development. 2012. V. 36. №. 1. P. 11–18.

3. Beach S.R.H., Brody G.H., Todorov A.A., Gunter T.D., Philibert R.A. Methylation at 5HTT mediates the impact of child sex abuse on women’s antisocial behavior: an examination of the Iowa adoptee sample // Psychosomatic Medicine. 2011. V. 73. №. 1. P. 83–87.

4. Bet P.M., Penninx B.W.J.H., Bochdanovits Z., Uitterlinden A.G., Beekman A.T.F., van Schoor N.M., Deeg D.J.H., Hoogendijk W.J.G. Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene-environment interaction // American Journ. of Medical Genetics. 2009. V. 150B. №. 5. P. 660–669.

5. Brunner D., Hen R. Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice // Ann NY Acad Sci. 1997. V. 836. №. 212. P. 81–105.

6. Buhot M.-C., Martin S., Segu L. Role of serotonin in memory impairment // Annals of Medicine. 2000. V. 32. №. 3. P. 210–221.

7. Caspi A., Sugden K., Moffitt T.E., Taylor A., Craig I.W., Harrington H.L., McClay J., Mill J., Martin J., Braithwaite A., Poulton R. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene // Science. 2003. V. 301. №. 5631. P. 386–389.

8. Chau C.M.Y., Ranger M., Sulistyoningrum D., Devlin A.M., Oberlander T.F., Grunau R.E. Neonatal Pain and COMT Val158Met Genotype in Relation to Serotonin Transporter (SLC6A4) Promoter Methylation in Very Preterm Children at School Age // Frontiers in Behavioral Neuroscience. 2014. V. 8. P. 1–12.

9. Cicchetti D., Handley E.D. Methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), in maltreated and nonmaltreated children: Associations with behavioral undercontrol, emotional lability/negativity, and externalizing and internalizi // Development and Psychopathology. 2017. V. 29. №. 5. P. 1795–1806.

10. Davis-Kean P.E. The influence of parent education and family income on child achievement: The indirect role of parental expectations and the home environment // Journ. of Family Psychology. 2005. V. 19. №. 2. P. 294–304.

11. Duman E.A., Canli T. Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males // Biology of Mood and Anxiety Disorders. 2015. V. 5. №. 1. P. 1–14.

12. Finger E.C., Marsh A.A., Buzas B., Kamel N., Rhodes R., Vythilingham M., Pine D.S., Goldman D., Blair J.R. The impact of tryptophan depletion and 5-HTTLPR genotype on passive avoidance and response reversal instrumental learning tasks // Neuropsychopharmacology. 2007. V. 32. №. 1. P. 206–215.

13. Francis D., Diorio J., Liu D., Meaney M.J. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science. 1999. V. 286. №. 5442. P. 1155–1158.

14. Frodl T., Szyf M., Carballedo A., Ly V., Dymov S., Vaisheva F., Morris D., Fahey C., Meaney J., Gill M., Booij L. DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli // Journ. of Psychiatry & Neuroscience. 2015. V. 40. №. 5. P. 296–305.

15. Gao Y., Raine A., Venables P.H., Dawson M.E., Mednick S.A. Reduced electrodermal fear conditioning from ages 3 to 8 years is associated with aggressive behavior at age 8 years // Journ. of Child Psychology and Psychiatry, and Allied Disciplines. 2010. V. 51. №. 5. P. 550–558.

16. Gao Y., Raine A., Venables P.H., Dawson M.E., Mednick S.A. Association of poor childhood fear conditioning and adult crime // American Journ. of Psychiatry. 2010. V. 167. №. 1. P. 56–60.

17. Garpenstrand H., Annas P., Ekblom J., Oreland L., Fredrikson M. Human fear conditioning is related to dopaminergic and serotonergic biological markers // Behavioral Neuroscience. 2001. V. 115. №. 2. P. 358–364.

18. Gotlib I.H., Joormann J., Minor K.L., Hallmayer J. HPA Axis Reactivity: A Mechanism Underlying the Associations Among 5-HTTLPR, Stress, and Depression // Biological Psychiatry. 2008. V. 63. №. 9. P. 847–851.

19. Gottlieb G., Lickliter R. Probabilistic epigenesis// Developmental Science. 2007. V. 10. № 1. P. 1–11.

20. Gyurak A., Haase C. M., Sze J., Goodkind M. S., Coppola G., Lane J., Miller B.L., Levenson R.W. The effect of the serotonin transporter polymorphism (5-HTTLPR) on empathic and self-conscious emotional reactivity // Emotion. 2013. V. 13. №. 1. P. 25–35.

21. Hankin B.L., Nederhof E., Oppenheimer C.W., Jenness J., Young J.F., Abela J.R.Z., Smolen A., Ormel J., Oldehinkel A.J. Differential susceptibility in youth: Evidence that 5-HTTLPR x positive parenting is associated with positive affect for better and worse // Translational Psychiatry. 2011. V. 1. №. 9. P. e44-7.

22. Heinz A., Braus D F., Smolka M.N., Wrase J., Puls I., Hermann D., Klein S., Grüsser S.M., Flor H., Schumann G., Mann K., Büchel C. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter // Nature Neuroscience. 2005. V. 8. №. 1. P. 20–21.

23. Isley S., O’Neil R., Clatfelter D., Parke R. Parent and child expressed affect and children’s social competence: Modeling direct and indirect pathways // Development Psychopathology. 1999. V. 35. №. 2. P. 547–560.

24. Jacobson L., Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis // Endocrine Reviews. 1991. V. 12. №. 2. P. 118–134.

25. Kang H., Kim J., Stewart R., Kim S., Bae K., Kim S., Bae K., Kim S., Shin I., Shin M., Yoon J. Progress in Neuro-Psychopharmacology & Biological Psychiatry Association of SLC6A4 methylation with early adversity , characteristics and outcomes in depression // Progress in Neuropsychopharmacology & Biological Psychiatry. 2013. V. 44, 23–28.

26. Kumsta R., Stevens S., Brookes K., Schlotz W., Castle J., Beckett C., Kreppner J., Rutter M., Sonuga-Barke E. 5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: Evidence from the English and Romanian Adoptee (ERA) study // Journ. of Child Psychology and Psychiatry and Allied Disciplines. 2010. V. 51. №. 7. P. 755–762.

27. LaBar K.S., Gatenby J.C., Gore J.C., LeDoux J.E., Phelps E.A. Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study // Neuron. 1998. V. 20. №. 5. P. 937–945.

28. Lesch K.P., Bengel D., Heils A., Sabol S.Z., Greenberg B.D., Petri S., Benjamin J., Muller C.R., Hamer D.H., Murphy D.L. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region // Science. 1996. V. 274. №. 5292. P. 1527–1531.

29. Liu D., Diorio J., Day J. C., Francis D. D., Meaney M.J. Maternal care, hippocampal synaptogenesis and cognitive development in rats // Nature Neuroscience. 2000. V. 3. №. 8. P. 799–806.

30. Lovic V., Gonzalez A., Fleming A.S. Maternally Separated Rats Show Deficits in Maternal Care in Adulthood // Developmental Psychobiology. 2001. V. 39. № 1. P. 19–33.

31. Lucki I. The spectrum of behaviors influenced by serotonin // Biological Psychiatry. 1998. V. 44. №. 3. P. 151–162.

32. McGowan P.O., Sasaki A., D’Alessio A.C., Dymov S., Labonté B., Szyf M., Turecki G., Meaney M.J. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse // Nature Neuroscience. 2009. V. 12. №. 3. P. 342–348.

33. Montirosso R., Provenzi L., Tavian D., Morandi F., Bonanomi A., Missaglia S., Tronick E., Borgatti R. Social stress regulation in 4-month-old infants: contribution of maternal social engagement and infants’ 5-HTTLPR genotype // Early Human Development. 2015. V. 91. №. 3. P. 173–179.

34. Nagy C., Turecki G. Sensitive periods in epigenetics: Bringing us closer to complex behavioral phenotypes // Epigenomics. 2012. V. 4. №. 4. P. 445–457.

35. Naumova O.Y., Lee M., Koposov R., Szyf M., Dozier M., Grigorenko E.L. Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents // Development and Psychopathology. 2012. V. 24. №. 1. 143–155.

36. Non A.L., Hollister B.M., Humphreys K.L., Childebayeva A., Esteves K., Zeanah C.H., Fox N.A., Nelson C.A., Drury S.S. DNA methylation at stress-related genes is associated with exposure to early life institutionalization // American Journ. of Physical Anthropology. 2016. V. 161. №. 1. P. 84–93.

37. Ouellet-Morin I., Wong C.C. Y., Danese A., Pariante C.M., Papadopoulos A.S., Mill J., Arseneault L. Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins // Psychological Medicine. 2013. V. 43. №. 9. P. 1813–1823.

38. Pagliaccio D., Luby J.L., Bogdan R., Agrawal A., Gaffrey M.S., Belden A.C., Botteron K.N., Harms M.P., Barch D.M. Stress-system genes and life stress predict cortisol levels and amygdala and hippocampal volumes in children // Neuropsychopharmacology. 2014. V. 39. №. 5. P. 1245–1253.

39. Parade S.H., Ridout K.K., Seifer R., Armstrong D.A., Marsit C.J., McWilliams M.A., Tyrka A.R. Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links With Internalizing Behavior Problems // Child Development. 2016. V. 87. №. 1. P. 86–97.

40. Porter R.J., Gallagher P., Watson S., Young A.H. Corticosteroid-serotonin interactions in depression: A review of the human evidence // Psychopharmacology. 2004. V. 173. №. 1. P. 1–17.

41. Provenzi L., Fumagalli M., Sirgiovanni I., Giorda R., Pozzoli U., Morandi F., Beri S., Menozzi G., Mosca F., Borgatti R., Montirosso R. Pain-related stress during the Neonatal Intensive Care Unit stay and SLC6A4 methylation in very preterm infants // Frontiers in Behavioral Neuroscience. 2015. V. 9. P. 1–9.

42. Ptashne M. On the use of the word “epigenetic” // Current Biology. 2007. V. 17. №. 7. P. R233–236.

43. Reif A., Rösler M., Freitag C.M., Schneider M., Eujen A., Kissling C., Wenzler D., Jacob C.P., Retz-Junginger P., Thome J., Lesch K.-P., Retz W. Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment // Neuropsychopharmacology. 2007. V. 32. №. 11. P. 2375–2383.

44. Rovaris D.L., Mota N.R., Bertuzzi G.P., Aroche A.P., Callegari-Jacques S.M., Guimarães L.S.P., Pezzi J.C., Viola T.W., Bau C.H.D., Grassi-Oliveira R. Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment // Journ. of Psychiatric Research. 2015. V. 68. P. 83–90.

45. Spangler G., Johann M., Ronai Z., Zimmermann P. Genetic and environmental influence on attachment disorganization // Journ. of Child Psychology and Psychiatry, and Allied Disciplines. 2009. V. 50. №. 8. P. 952–961.

46. Summers C.H., Korzan W.J., Lukkes J.L., Watt M.J., Forster G.L., Øverli Ø., Höglund E., Larson E.T., Ronan P.J., Matter J.M., Summers T.R., Renner K.J., Greenberg N. Does serotonin influence aggression? comparing regional activity before and during social interaction // Physiological and Biochemical Zoology. 2005. V. 78. №. 5. P. 679–694.

47. Vijayendran M., Beach S.R.H., Plume J.M., Brody G.H., Philibert R.A. Effects of genotype and child abuse on DNA methylation and gene expression at the serotonin transporter // Frontiers in Psychiatry. 2012. V. 3. P. 1–7.

48. Vukojevic V., Kolassa I.-T., Fastenrath M., Gschwind L., Spalek K., Milnik A., Heck A., Vogler C., Wilker S., Demougin P., Peter F., Atucha E., Stetak A., Roozendaal B., Elbert T., Papassotiropoulos A., de Quervain D. J.-F. Epigenetic Modification of the Glucocorticoid Receptor Gene Is Linked to Traumatic Memory and Post-Traumatic Stress Disorder Risk in Genocide Survivors // Journ. of Neuroscience. 2014. V. 34. №. 31. P. 10274–10284.

49. Waddington C. H. The strategy of the genes: a discussion of some aspects of theoretical biology. London: Allen & Unwin, 1957.

50. Way B.M., Taylor S.E. The serotonin transporter promoter polymorphism is associated with cortisol response to psychosocial stress // Biological Psychiatry. 2010. V. 67. №. 5. P. 487–492.

51. Weaver I.C.G., Cervoni N., Champagne F. A., D’Alessio A.C., Sharma S., Seckl J.R., Dymov S., Szyf M., Meaney M.J. Epigenetic programming by maternal behavior // Nature Neuroscience. 2004. V. 7. №. 8. P. 847–854.

52. Weder N., Zhang H., Jensen K., Yang B.Z., Simen A., Jackowski A., Lipschitz D., Douglas-Palumberi H., Ge M., Perepletchikova F., O'Loughlin K., Hudziak J.J., Gelernter J., Kaufman J. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry // Journ. of the American Academy of Child and Adolescent Psychiatry. 2014. V. 53. №. 4. P. 417–24.e5.

53. Weinberg J., Levine S. Early handling influences on behavioral and physiological responses during active avoidance // Developmental Psychobiology. 1977. V. 10. №. 2. P. 161–169.

54. Wickrama K.A.S., Conger R.D., Abraham W.T. Early adversity and later health: the intergenerational transmission of adversity through mental disorder and physical illness. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 2005. V. 60. № 2. P. 125–129.

55. Wüst S., van Rossum E.F.C., Federenko I.S., Koper J.W., Kumsta R., Hellhammer D.H. Common Polymorphisms in the Glucocorticoid Receptor Gene Are Associated with Adrenocortical Responses to Psychosocial Stress // The Journ. of Clinical Endocrinology & Metabolism. 2004. V. 89. №. 2. P. 565–573.

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