Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-06T12:14:43.597Z Has data issue: false hasContentIssue false
  • English
  • Français

Epigenetic alterations related to early-life stressful events

Published online by Cambridge University Press:  24 June 2014

Raúl Ventura-Junca  and
Luisa M. Herrera
Raúl Ventura-Junca
Affiliation:
School of Psychology, Universidad de los Andes, Santiago, Chile Human Genetics Program, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
Luisa M. Herrera*
Affiliation:
Human Genetics Program, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
*
Luisa Herrera, Programa de Genética Humana, ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Independencia, Santiago, Chile. Tel: 562 9786976; Fax: 562 7373158; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Extract

Objective: Early stress events severely impact brain and behaviour. From a neurobiological point of view early stress influences neuroanatomical structures and is associated with a dysregulation of the hypothalamic-pituitary-adrenal axis. The objective of this article is to review the epigenetic alterations implicated in brain adaptation to early stress events.

Method: A review of empirical research of epigenetic alterations associated to early stress events was performed.

Results: Neuroanatomic and epigenetic alterations have been observed after early stress events. Epigenetics alterations include DNA methylation, histones modifications and microRNA (miRNA) expression. The most studied is largely the former, affecting genes involved in neuroendocrine, neurotransmission and neuroplasticity regulation after early stress exposition. It includes glucocorticoid receptor, FK506-binding protein 5, arginine vasopressin, oestrogen receptor alpha, 5-hydroxy-tryptamine transporter and brain-derived neurotrophic factor.

Conclusion: Epigenetic regulation is critical in the interplay between nature and nurture. Alterations in the DNA methylation as well as histones modifications and miRNA expression patterns could explain abnormal behaviours secondary to early stress events.

Keywords

behaviourearly stressepigeneticHPAmethylation
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 5 , October 2012 , pp. 255 - 265
Copyright
Copyright © Cambridge University Press 2012

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

1Ramiro, LS, Madrid, BJ, Brown, DW. Adverse childhood experiences (ACE) and health-risk behaviors among adults in a developing country setting. Child Abuse Negl 2010;34:842–855.CrossRefGoogle Scholar
2Van Der Vegt, EJ, Tieman, W, Van Der Ende, J, Ferdinand, RF, Verhulst, FC, Tiemeier, H. Impact of early childhood adversities on adult psychiatric disorders: a study of international adoptees. Soc Psychiatry Psychiatr Epidemiol 2009;44:724–731.CrossRefGoogle ScholarPubMed
3Mclaughlin, KA, Green, JG, Gruber, MJ, Sampson, NA, Zaslavsky, AM, Kessler, RC. Childhood adversities and adult psychopathology in the National Comorbidity Survey Replication (NCS-R) III: associations with functional impairment related to DSM-IV disorders. Psychol Med 2010;40:847–859.CrossRefGoogle ScholarPubMed
4Alloy, LB, Abramson, LY, Smith, JM, Gibb, BE, Neeren, AM. Role of parenting and maltreatment histories in unipolar and bipolar mood disorders: mediation by cognitive vulnerability to depression. Clin Child Fam Psychol Rev 2006;9:23–64.CrossRefGoogle ScholarPubMed
5Kessler, RC, Davis, CG, Kendler, KS. Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey. Psychol Med 1997;27:1101–1119.CrossRefGoogle ScholarPubMed
6Afifi, TO, Mather, A, Boman, J et al. . Childhood adversity and personality disorders: Results from a nationally representative population-based study. J Psychiatr Res 2011;45:814–822.CrossRefGoogle ScholarPubMed
7Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR, Walters, EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593–602.CrossRefGoogle ScholarPubMed
8Belsky, J, Steinberg, L, Houts, RM, Halpern-Felsher, BL. The development of reproductive strategy in females: early maternal harshness → earlier menarche → increased sexual risk taking. Dev Psychol 2010;46:120–128.CrossRefGoogle ScholarPubMed
9Beck, AT. The evolution of the cognitive model of depression and its neurobiological correlates. Am J Psychiatry 2008;165:969–977.CrossRefGoogle ScholarPubMed
10 xmO. Child Maltreatment. World Health Organization Fact Sheet No. 150, 2010.Google Scholar
11Herman, JP, Ostrander, MM, Mueller, NK, Figueiredo, H. Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:1201–1213.CrossRefGoogle ScholarPubMed
12Penza, KM, Heim, C, Nemeroff, CB. Neurobiological effects of childhood abuse: implications for the pathophysiology of depression and anxiety. Arch Womens Ment Health 2003;6:15–22.CrossRefGoogle ScholarPubMed
13Jackowski, A, Perera, TD, Abdallah, CG et al. . Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates. Psychiatry Res 2011;192:37–44.CrossRefGoogle ScholarPubMed
14Vythilingam, M, Heim, C, Newport, J et al. . Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry 2002;159:2072–2080.CrossRefGoogle ScholarPubMed
15Driessen, M, Herrmann, J, Stahl, K et al. . Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 2000;57:1115–1122.CrossRefGoogle ScholarPubMed
16Mirescu, C, Gould, E. Stress and adult neurogenesis. Hippocampus 2006;16:233–238.CrossRefGoogle ScholarPubMed
17Mcewen, BS. Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 2005;54:20–23.CrossRefGoogle ScholarPubMed
18Liston, C, Miller, MM, Goldwater, DS et al. . Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting. J Neurosci 2006;26:7870–7874.CrossRefGoogle ScholarPubMed
19Radley, JJ, Sisti, HM, Hao, J et al. . Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 2004;125:1–6.CrossRefGoogle ScholarPubMed
20Mitra, R, Jadhav, S, Mcewen, BS, Vyas, A, Chattarji, S. Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala. Proc Natl Acad Sci USA 2005;102:9371–9376.CrossRefGoogle ScholarPubMed
21Vyas, A, Jadhav, S, Chattarji, S. Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala. Neuroscience 2006;143:387–393.CrossRefGoogle ScholarPubMed
22Woon, FL, Hedges, DW. Hippocampal and amygdala volumes in children and adults with childhood maltreatment-related posttraumatic stress disorder: a meta-analysis. Hippocampus 2008;18:729–736.CrossRefGoogle ScholarPubMed
23Pruessner, JC, Baldwin, MW, Dedovic, K et al. . Self-esteem, locus of control, hippocampal volume, and cortisol regulation in young and old adulthood. Neuroimage 2005;28:815–826.CrossRefGoogle Scholar
24Wilner, AP, De Varennes, B, Gregoire, PA, Lupien, S, Pruessner, JC. Glucocorticoids and hippocampal atrophy after heart transplantation. Ann Thorac Surg 2002;73:1965–1967.CrossRefGoogle ScholarPubMed
25De Bellis, MD, Keshavan, MS, Shifflett, H et al. . Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study. Biol Psychiatry 2002;52:1066–1078.CrossRefGoogle ScholarPubMed
26Nemeroff, CB, Vale, WW. The neurobiology of depression: inroads to treatment and new drug discovery. J Clin Psychiatry 2005;66(Suppl. 7):5–13.Google ScholarPubMed
27Engelmann, M, Landgraf, R, Wotjak, CT. The hypothalamic-neurohypophysial system regulates the hypothalamic-pituitary-adrenal axis under stress: an old concept revisited. Front Neuroendocrinol 2004;25:132–149.CrossRefGoogle ScholarPubMed
28Aguilera, G, Rabadan-Diehl, C. Vasopressinergic regulation of the hypothalamic-pituitary-adrenal axis: implications for stress adaptation. Regul Pept 2000;96:23–29.CrossRefGoogle ScholarPubMed
29Sandi, C. Stress, cognitive impairment and cell adhesion molecules. Nature reviews. 2004;5:917–930.CrossRefGoogle ScholarPubMed
30Charmandari, E, Tsigos, C, Chrousos, G. Endocrinology of the stress response. Annu Rev Physiol 2005;67:259–284.CrossRefGoogle ScholarPubMed
31Rentesi, G, Antoniou, K, Marselos, M, Fotopoulos, A, Alboycharali, J, Konstandi, M. Long-term consequences of early maternal deprivation in serotonergic activity and HPA function in adult rat. Neurosci Lett 2010;480:7–11.CrossRefGoogle ScholarPubMed
32Heim, C, Mletzko, T, Purselle, D, Musselman, DL, Nemeroff, CB. The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biol Psychiatry 2008;63:398–405.CrossRefGoogle ScholarPubMed
33Weiss, EL, Longhurst, JG, Mazure, CM. Childhood sexual abuse as a risk factor for depression in women: psychosocial and neurobiological correlates. Am J Psychiatry 1999;156:816–828.CrossRefGoogle ScholarPubMed
34Shea, A, Walsh, C, Macmillan, H, Steiner, M. Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females. Psychoneuroendocrinology 2005;30:162–178.CrossRefGoogle ScholarPubMed
35Heim, C, Plotsky, PM, Nemeroff, CB. Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology 2004;29:641–648.CrossRefGoogle ScholarPubMed
36Rasmusson, AM, Lipschitz, DS, Wang, S et al. . Increased pituitary and adrenal reactivity in premenopausal women with posttraumatic stress disorder. Biol Psychiatry 2001;50:965–977.CrossRefGoogle ScholarPubMed
37Yehuda, R, Bierer, LM, Schmeidler, J, Aferiat, DH, Breslau, I, Dolan, S. Low cortisol and risk for PTSD in adult offspring of holocaust survivors. Am J Psychiatry 2000;157:1252–1259.CrossRefGoogle ScholarPubMed
38Holsboer, F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000;23:477–501.CrossRefGoogle ScholarPubMed
39Clarke, AS, Wittwer, DJ, Abbott, DH, Schneider, ML. Long-term effects of prenatal stress on HPA axis activity in juvenile rhesus monkeys. Dev Psychobiol 1994;27:257–269.CrossRefGoogle ScholarPubMed
40Liu, D, Diorio, J, Tannenbaum, B et al. . Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science (New York, NY) 1997;277:1659–1662.CrossRefGoogle ScholarPubMed
41Sterlemann, V, Ganea, K, Liebl, C et al. . Long-term behavioral and neuroendocrine alterations following chronic social stress in mice: implications for stress-related disorders. Horm Behav 2008;53:386–394.CrossRefGoogle ScholarPubMed
42Pryce, CR. Postnatal ontogeny of expression of the corticosteroid receptor genes in mammalian brains: Inter-species and intra-species differences. Brain Res Rev 2008;57:596–605.CrossRefGoogle ScholarPubMed
43Ridder, S, Chourbaji, S, Hellweg, R et al. . Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 2005;25:6243–6250.CrossRefGoogle ScholarPubMed
44Zhang, TY, Meaney, MJ. Epigenetics and the environmental regulation of the genome and its function. Annu Rev Psychol 2010;61(439–466):C431–433.CrossRefGoogle ScholarPubMed
45Caiafa, P, Zampieri, M. DNA methylation and chromatin structure: the puzzling CpG islands. J Cell Biochem 2005;94:257–265.CrossRefGoogle ScholarPubMed
46Bonasio, R, Tu, S, Reinberg, D. Molecular signals of epigenetic states. Science 2010;330:612–616.CrossRefGoogle ScholarPubMed
47Hoffmann, A. Spengler, D. Neuroscience: DNA memories of early social life, 2012.Google Scholar
48Szyf, M. DNA methylation and demethylation probed by small molecules. Biochim Biophys Acta 2010;1799:750–759.CrossRefGoogle ScholarPubMed
49Lee, JY, Lee, TH. Effects of histone acetylation and CpG methylation on the structure of nucleosomes. Biochim Biophys Acta 2012;1824:974–982.CrossRefGoogle ScholarPubMed
50Bannister, AJ, Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res 2011;21:381–395.CrossRefGoogle ScholarPubMed
51Margueron, R, Trojer, P, Reinberg, D. The key to development: interpreting the histone code? Curr Opin Genet Dev 2005;15:163–176.CrossRefGoogle ScholarPubMed
52Lessard, JA, Crabtree, GR. Chromatin regulatory mechanisms in pluripotency. Annu Rev Cell Dev Biol 2010;26:503–532.CrossRefGoogle ScholarPubMed
53Racki, LR, Narlikar, GJ. ATP-dependent chromatin remodeling enzymes: two heads are not better, just different. Curr Opin Genet Dev 2008;18:137–144.CrossRefGoogle Scholar
54Hota, SK, Bartholomew, B. Diversity of operation in ATP-dependent chromatin remodelers. Biochim Biophys Acta 2011;1809:476–487.CrossRefGoogle ScholarPubMed
55Erdel, F, Krug, J, Langst, G, Rippe, K. Targeting chromatin remodelers: signals and search mechanisms. Biochim Biophys Acta 2011;1809:497–508.CrossRefGoogle ScholarPubMed
56Magistri, M, Faghihi, MA, st. Laurent, G 3rd, Wahlestedt, C.Regulation of chromatin structure by long noncoding RNAs: focus on natural antisense transcripts. Trends Genet 2012;28:389–396.CrossRefGoogle ScholarPubMed
57Qureshi, IA, Mehler, MF.Epigenetic mechanisms underlying human epileptic disorders and the process of epileptogenesis. Neurobiol Disease 2010;39:53–60.CrossRefGoogle ScholarPubMed
58Davis-Dusenbery, BN, Hata, A. Mechanisms of control of microRNA biogenesis. J Biochem 2010;148:381–392.Google ScholarPubMed
59Saxena, A, Carninci, P. Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs. BioEssays: news and reviews in molecular, cellular and developmental biology. 2011;33:830–839.CrossRefGoogle ScholarPubMed
60Aalto, AP, Pasquinelli, AE. Small non-coding RNAs mount a silent revolution in gene expression. Curr Opin Cell Biol 2012;24:333–340.CrossRefGoogle Scholar
61Shukla, GC, Singh, J, Barik, S. MicroRNAs: processing, maturation, target recognition and regulatory functions. Molecular Cell Pharmacol 2011;3:83–92.Google ScholarPubMed
62Schratt, G. Fine-tuning neural gene expression with microRNAs. Curr Opin Neurobiol 2009;19:213–219.CrossRefGoogle ScholarPubMed
63Weaver, IC. Shaping adult phenotypes through early life environments. Birth Defects Res C Embryo Today 2009;87:314–326.CrossRefGoogle ScholarPubMed
64Lenroot, RK, Giedd, JN. Annual research review: developmental considerations of gene by environment interactions. J Child Psychol Psychiatry 2011;52:429–441.CrossRefGoogle ScholarPubMed
65Anda, RF, Felitti, VJ, Bremner, JD et al. . The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin Neurosci 2006;256:174–186.CrossRefGoogle ScholarPubMed
66Bradley, RG, Binder, EB, Epstein, MP et al. . Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene. Arch Gen Psychiatry 2008;65:190–200.CrossRefGoogle ScholarPubMed
67Chapman, DP, Whitfield, CL, Felitti, VJ, Dube, SR, Edwards, VJ, Anda, RF. Adverse childhood experiences and the risk of depressive disorders in adulthood. J Affect Disord 2004;82:217–225.CrossRefGoogle ScholarPubMed
68Szyf, M. The early life environment and the epigenome. Biochim Biophys Acta 2009;1790:878–885.CrossRefGoogle ScholarPubMed
69Meaney, MJ, Szyf, M, Seckl, JR. Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends Mol Med 2007;13:269–277.CrossRefGoogle ScholarPubMed
70Murgatroyd, C, Wu, Y, Bockmuhl, Y, Spengler, D. Genes learn from stress: how infantile trauma programs us for depression. Epigenetics 2010;5:194–199.CrossRefGoogle ScholarPubMed
71Champagne, FA. Epigenetic mechanisms and the transgenerational effects of maternal care. Front Neuroendocrinol 2008;29:386–397.CrossRefGoogle ScholarPubMed
72Mcleod, J, Sinal, CJ, Perrot-Sinal, TS. Evidence for non-genomic transmission of ecological information via maternal behavior in female rats. Genes Brain Behav 2007;6:19–29.CrossRefGoogle ScholarPubMed
73Franklin, TB, Russig, H, Weiss, IC et al. . Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 2010;68:408–415.CrossRefGoogle Scholar
74Fernandez-Guasti, A, Fiedler, JL, Herrera, L, Handa, RJ. Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones. Horm Metab Res 2012;44:607–618.Google ScholarPubMed
75Weaver, IC, Cervoni, N, Champagne, FA et al. . Epigenetic programming by maternal behavior. Nat Neurosci 2004;7:847–854.CrossRefGoogle ScholarPubMed
76Murgatroyd, C, Spengler, D. Epigenetics of early child development. Front Psychiatry/Front Res Found 2011;2:16.Google ScholarPubMed
77Uchida, S, Hara, K, Kobayashi, A et al. . Early life stress enhances behavioral vulnerability to stress through the activation of REST4-mediated gene transcription in the medial prefrontal cortex of rodents. J Neurosci 2010;30:15007–15018.CrossRefGoogle ScholarPubMed
78Levine, A, Worrell, TR, Zimnisky, R, Schmauss, C. Early life stress triggers sustained changes in histone deacetylase expression and histone H4 modifications that alter responsiveness to adolescent antidepressant treatment. Neurobiol Dis 2012;45:488–498.CrossRefGoogle ScholarPubMed
79Tognini, P, Pizzorusso, T. MicroRNA212/132 family: molecular transducer of neuronal function and plasticity. Int J Biochem Cell Biol 2012;44:6–10.CrossRefGoogle ScholarPubMed
80Weaver, IC. Epigenetic effects of glucocorticoids. Semin Fetal Neonatal Med 2009;14:143–150.CrossRefGoogle ScholarPubMed
81Maestripieri, D. Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys. Proc Natl Acad Sci USA 2005;102:9726–9729.CrossRefGoogle ScholarPubMed
82Zhang, TY, Bagot, R, Parent, C et al. . Maternal programming of defensive responses through sustained effects on gene expression. Biol Psychol 2006;73:72–89.CrossRefGoogle ScholarPubMed
83Bagot, RC, Van Hasselt, FN, Champagne, DL, Meaney, MJ, Krugers, HJ, Joels, M. Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus. Neurobiol Learn Mem 2009;92:292–300.CrossRefGoogle ScholarPubMed
84Szyf, M, Weaver, IC, Champagne, FA, Diorio, J, Meaney, MJ. Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat. Front Neuroendocrinol 2005;26:139–162.CrossRefGoogle ScholarPubMed
85Weaver, IC, D'Alessio, AC, Brown, SE et al. . The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes. J Neurosci 2007;27:1756–1768.CrossRefGoogle ScholarPubMed
86Cervoni, N, Szyf, M. Demethylase activity is directed by histone acetylation. J Biol Chem 2001;276:40778–40787.CrossRefGoogle ScholarPubMed
87Mcgowan, PO, Sasaki, A, D'Alessio, AC et al. . Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009;12:342–348.CrossRefGoogle ScholarPubMed
88Alt, SR, Turner, JD, Klok, MD et al. . Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology 2009;35:544–556.CrossRefGoogle Scholar
89Binder, EB, Salyakina, D, Lichtner, P et al. . Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 2004;36:1319–1325.CrossRefGoogle ScholarPubMed
90Willour, VL, Chen, H, Toolan, J et al. . Family-based association of FKBP5 in bipolar disorder. Mol Psychiatry 2009;14:261–268.CrossRefGoogle ScholarPubMed
91Binder, EB, Bradley, RG, Liu, W et al. . Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008;299:1291–1305.CrossRefGoogle ScholarPubMed
92Brent, D, Melhem, N, Ferrell, R et al. . Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Am J Psychiatry 2010;167:190–197.CrossRefGoogle ScholarPubMed
93Supriyanto, I, Sasada, T, Fukutake, M et al. . Association of FKBP5 gene haplotypes with completed suicide in the Japanese population. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:252–256.CrossRefGoogle ScholarPubMed
94Luijk, MP, Velders, FP, Tharner, A et al. . FKBP5 and resistant attachment predict cortisol reactivity in infants: gene-environment interaction. Psychoneuroendocrinology 2010;35:1454–1461.CrossRefGoogle ScholarPubMed
95Shibuya, N, Suzuki, A, Sadahiro, R et al. . Association study between a functional polymorphism of FK506-binding protein 51 (FKBP5) gene and personality traits in healthy subjects. Neurosci Lett 2010;485:194–197.CrossRefGoogle ScholarPubMed
96Hartmann, J, Wagner, KV, Liebl, C et al. . The involvement of FK506-binding protein 51 (FKBP5) in the behavioral and neuroendocrine effects of chronic social defeat stress. Neuropharmacology 2012;62:332–339.CrossRefGoogle ScholarPubMed
97Lee, RS, Tamashiro, KL, Yang, X et al. . Chronic corticosterone exposure increases expression and decreases deoxyribonucleic acid methylation of Fkbp5 in mice. Endocrinology 2010;151:4332–4343.CrossRefGoogle ScholarPubMed
98Murgatroyd, C, Patchev, AV, Wu, Y et al. . Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci 2009;12:1559–1566.CrossRefGoogle ScholarPubMed
99Lopez-Leon, S, Janssens, AC, Gonzalez-Zuloeta Ladd, AM et al. . Meta-analyses of genetic studies on major depressive disorder. Mol Psychiatry 2007;13:772–785.CrossRefGoogle ScholarPubMed
100Sarapas, C, Cai, G, Bierer, LM et al. . Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks. Dis Markers 2011;30:101–110.CrossRefGoogle ScholarPubMed
101Mcewen, BS, Alves, SE. Estrogen actions in the central nervous system. Endocr Rev 1999;20:279–307.Google ScholarPubMed
102Weiser, MJ, Foradori, CD, Handa, RJ. Estrogen receptor beta in the brain: from form to function. Brain Res Rev 2008;57:309–320.CrossRefGoogle ScholarPubMed
103Bodo, C, Rissman, EF. New roles for estrogen receptor beta in behavior and neuroendocrinology. Front Neuroendocrinol 2006;27:217–232.CrossRefGoogle ScholarPubMed
104Kirschbaum, C, Kudielka, BM, Gaab, J, Schommer, NC, Hellhammer, DH. Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 1999;61:154–162.CrossRefGoogle ScholarPubMed
105Kumsta, R, Entringer, S, Koper, JW, Van Rossum, EF, Hellhammer, DH, Wust, S. Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. Biol Psychiatry 2007;62:863–869.CrossRefGoogle ScholarPubMed
106Cameron, NM, Shahrokh, D, Del Corpo, A et al. . Epigenetic programming of phenotypic variations in reproductive strategies in the rat through maternal care. J Neuroendocrinol 2008;20:795–801.CrossRefGoogle ScholarPubMed
107Caspi, A, Sugden, K, Moffitt, TE et al. . Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003;301:386–389.CrossRefGoogle ScholarPubMed
108Lesch, KP, Bengel, D, Heils, A et al. . Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996;274:1527–1531.CrossRefGoogle ScholarPubMed
109Kendler, KS, Kuhn, JW, Vittum, J, Prescott, CA, Riley, B. The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Arch Gen Psychiatry 2005;62:529–535.CrossRefGoogle Scholar
110Murphy, DL, Moya, PR. Human serotonin transporter gene (SLC6A4) variants: their contributions to understanding pharmacogenomic and other functional GxG and GxE differences in health and disease. Curr Opin Pharmacol 2011;11:3–10.CrossRefGoogle Scholar
111Alessandro, S, Kato, M. The serotonin transporter gene and effectiveness of SSRIs. Expert Rev Neurother 2008;8:111–120.Google Scholar
112Karg, K, Burmeister, M, Shedden, K, Sen, S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 2011;68:444–454.CrossRefGoogle ScholarPubMed
113Philibert, R, Madan, A, Andersen, A, Cadoret, R, Packer, H, Sandhu, H. Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island. Am J Med Genet B Neuropsychiatr Genet 2007;144B:101–105.CrossRefGoogle ScholarPubMed
114Van Ijzendoorn, MH, Caspers, K, Bakermans-Kranenburg, MJ, Beach, SR, Philibert, R. Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma. Biol Psychiatry 2010;68:405–407.CrossRefGoogle ScholarPubMed
115Kochanska, G, Philibert, RA, Barry, RA. Interplay of genes and early mother-child relationship in the development of self-regulation from toddler to preschool age. J Child Psychol Psychiatry 2009;50:1331–1338.CrossRefGoogle ScholarPubMed
116Devlin, AM, Brain, U, Austin, J, Oberlander, TF. Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth. PLoS One 2010;5:e12201.CrossRefGoogle ScholarPubMed
117Oberlander, TF, Weinberg, J, Papsdorf, M, Grunau, R, Misri, S, Devlin, AM. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 2008;3:97–106.CrossRefGoogle ScholarPubMed
118Russo-Neustadt, A. Brain-derived neurotrophic factor, behavior, and new directions for the treatment of mental disorders. Semin Clin Neuropsychiatry 2003;8:109–118.CrossRefGoogle ScholarPubMed
119Angelucci, F, Brene, S, Mathe, AA. BDNF in schizophrenia, depression and corresponding animal models. Mol Psychiatry 2005;10:345–352.CrossRefGoogle ScholarPubMed
120Colzato, LS, Van Der Does, AJ, Kouwenhoven, C, Elzinga, BM, Hommel, B. BDNF Val(66)Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults. Psychoneuroendocrinology 2011;36:1562–1569.CrossRefGoogle ScholarPubMed
121Karege, F, Perret, G, Bondolfi, G, Schwald, M, Bertschy, G, Aubry, JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 2002;109:143–148.CrossRefGoogle ScholarPubMed
122Aydemir, O, Deveci, A, Taneli, F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:261–265.CrossRefGoogle ScholarPubMed
123Magarinos, AM, Mcewen, BS, Flugge, G, Fuchs, E. Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci 1996;16:3534–3540.CrossRefGoogle ScholarPubMed
124Murakami, S, Imbe, H, Morikawa, Y, Kubo, C, Senba, E. Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res 2005;53:129–139.CrossRefGoogle ScholarPubMed
125Smith, MA, Makino, S, Kvetnansky, R, Post, RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 1995;15:1768–1777.CrossRefGoogle ScholarPubMed
126Taliaz, D, Stall, N, Dar, DE, Zangen, A. Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol Psychiatry 2010;15:80–92.CrossRefGoogle ScholarPubMed
127Taliaz, D, Loya, A, Gersner, R, Haramati, S, Chen, A, Zangen, A. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor. J Neurosci 2011;31:4475–4483.CrossRefGoogle ScholarPubMed
128Tapia-Arancibia, L, Rage, F, Givalois, L, Arancibia, S. Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 2004;25:77–107.CrossRefGoogle ScholarPubMed
129 xml:id="acn683-cit-0129">Patapoutian, A, Reichardt, LF. Trk receptors: mediators of neurotrophin action. Curr Opin Neurobiol 2001;11:272–280.CrossRefGoogle ScholarPubMed
130Carlezon, WA Jr, Duman, RS, Nestler, EJ. The many faces of CREB. Trends Neurosci 2005;28:436–445.CrossRefGoogle ScholarPubMed
131Roth, TL, Lubin, FD, Funk, AJ, Sweatt, JD. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry 2009;65:760–769.CrossRefGoogle ScholarPubMed
132Roth, TL, Sweatt, JD. Epigenetic marking of the BDNF gene by early-life adverse experiences. Horm Behav 2011;59:315–320.CrossRefGoogle ScholarPubMed
133Lubin, FD, Roth, TL, Sweatt, JD. Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 2008;28:10576–10586.CrossRefGoogle ScholarPubMed
134Branchi, I, Francia, N, Alleva, E. Epigenetic control of neurobehavioural plasticity: the role of neurotrophins. Behav Pharmacol 2004;15:353–362.CrossRefGoogle ScholarPubMed
135Fumagalli, F, Molteni, R, Racagni, G, Riva, MA. Stress during development: Impact on neuroplasticity and relevance to psychopathology. Prog Neurobiol 2007;81:197–217.CrossRefGoogle ScholarPubMed
136Lippmann, M, Bress, A, Nemeroff, CB, Plotsky, PM, Monteggia, LM. Long-term behavioural and molecular alterations associated with maternal separation in rats. Eur J Neurosci 2007;25:3091–3098.CrossRefGoogle ScholarPubMed
137Zhang, TY, Parent, C, Weaver, I, Meaney, MJ. Maternal programming of individual differences in defensive responses in the rat. Ann N Y Acad Sci 2004;1032:85–103.CrossRefGoogle ScholarPubMed
138Balbernie, R. Reactive attachment disorder as an evolutionary adaptation. Attach Hum Dev 2010;12:265–281.CrossRefGoogle ScholarPubMed
139Crews, D. Epigenetics and its implications for behavioral neuroendocrinology. Front Neuroendocrinol 2008;29:344–357.CrossRefGoogle ScholarPubMed