Skip to main content Accessibility help

Behavioral epigenetics and the developmental origins of child mental health disorders

  • B. M. Lester (a1) (a2) (a3) (a4), C. J. Marsit (a5), E. Conradt (a1) (a4), C. Bromer (a6) and J. F. Padbury (a3) (a4)...


Advances in understanding the molecular basis of behavior through epigenetic mechanisms could help explain the developmental origins of child mental health disorders. However, the application of epigenetic principles to the study of human behavior is a relatively new endeavor. In this paper we discuss the ‘Developmental Origins of Health and Disease’ including the role of fetal programming. We then review epigenetic principles related to fetal programming and the recent application of epigenetics to behavior. We focus on the neuroendocrine system and develop a simple heuristic stress-related model to illustrate how epigenetic changes in placental genes could predispose the infant to neurobehavioral profiles that interact with postnatal environmental factors potentially leading to mental health disorders. We then discuss from an ‘Evo-Devo’ perspective how some of these behaviors could also be adaptive. We suggest how elucidation of these mechanisms can help to better define risk and protective factors and populations at risk.


Corresponding author

*Address for correspondence: Dr B. Lester, Department of Pediatrics, Brown Center for Children, Women and Infants Hospital, 101 Dudley Street, Providence, RI, 02905 USA. (E-mails


Hide All
1.Barker, DJ, Osmond, C, Rodin, I, Fall, CH, Winter, PD. Low weight gain in infancy and suicide in adult life. BMJ. 1995; 311, 1203.
2.Gluckman, PD, Hanson, MA. Living with the past: evolution, development, and patterns of disease. Science. 2004; 305, 17331736.
3.Welberg, LA, Seckl, JR. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol. 2001; 13, 113128.
4.Barker, DJ, Osmond, C. Low birth weight and hypertension. BMJ. 1988; 297, 134135.
5.Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577580.
6.Barker, D. Mothers, Babies and Health in Later Life, 1998. Churchill Livingstone: Edinburgh and New York.
7.Gluckman, PD, Hanson, MA. Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res. 2004; 56, 311317.
8.Barker, DJ. Fetal programming of coronary heart disease. Trends Endocrinol Metab. 2002; 13, 364368.
9.Barker, DJ, Osmond, C, Golding, J, Kuh, D, Wadsworth, ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298, 564567.
10.Falkner, B. Birth weight as a predictor of future hypertension. Am J Hypertens. 2002; 15(Pt 2), 43S45S.
11.Hales, CN, Barker, DJ, Clark, PM, et al.Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991; 303, 10191022.
12.McMillen, IC, Robinson, JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005; 85, 571633.
13.Pfister, HP, Muir, JL. Prenatal exposure to predictable and unpredictable novelty stress and oxytocin treatment affects offspring development and behavior in rats. Int J Neurosci. 1992; 62, 227241.
14.Rich-Edwards, J, Colditz, G, Stampfer, M, et al.Birthweight and the risk for type 2 diabetes mellitus in adult women. Ann Intern Med. 1999; 130, 278284.
15.Sallout, B, Walker, M. The fetal origin of adult diseases. J Obstet Gynaecol. 2003; 23, 555560.
16.Stein, CE, Fall, CH, Kumaran, K, et al. Fetal growth and coronary heart disease in south India. Lancet. 1996; 348, 12691273.
17.Allin, M, Rooney, M, Cuddy, M, et al. Personality in young adults who are born preterm. Pediatrics. 2006; 117, 309316.
18.Gale, CR, Martyn, CN. Birth weight and later risk of depression in a national birth cohort. Br J Psychiatry. 2004; 184, 2833.
19.Thompson, C, Syddall, H, Rodin, I, Osmond, C, Barker, DJ. Birth weight and the risk of depressive disorder in late life. Br J Psychiatry. 2001; 179, 450455.
20.Wals, M, Reichart, CG, Hillegers, MH, et al. Impact of birth weight and genetic liability on psychopathology in children of bipolar parents. J Am Acad Child Adolesc Psychiatry. 2003; 42, 11161121.
21.Cannon, TD, Rosso, IM. Levels of analysis in etiological research on schizophrenia. Dev Psychopathol. 2002; 14, 653666.
22.Alati, R, Lawlor, DA, Mamun, AA, et al. Is there a fetal origin of depression? Evidence from the Mater University Study of Pregnancy and its Outcomes. Am J Epidemiol. 2007; 165, 575582.
23.Cheung, YB. Early origins and adult correlates of psychosomatic distress. Soc Sci Med. 2002; 55, 937948.
24.Cheung, YB, Khoo, KS, Karlberg, J, Machin, D. Association between psychological symptoms in adults and growth in early life: longitudinal follow up study. BMJ. 2002; 325, 749.
25.Wiles, NJ, Peters, TJ, Leon, DA, Lewis, G. Birth weight and psychological distress at age 45–51 years: results from the Aberdeen Children of the 1950s cohort study. Br J Psychiatry. 2005; 187, 2128.
26.Schlotz, W, Phillips, DI. Fetal origins of mental health: evidence and mechanisms. Brain Behav Immun. 2009; 23, 905916.
27.Ravelli, AC, van Der Meulen, JH, Osmond, C, Barker, DJ, Bleker, OP. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr. 1999; 70, 811816.
28.Ravelli, GP, Stein, ZA, Susser, MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976; 295, 349353.
29.Van Ijzendoorn, M, Bakermans-Kranenburg, M, Ebstein, R. Methylation matters in child development: toward developmental behavioral epigenetics. Child Dev Perspect. 2011; 5, 305310.
30.Van den Bergh, BRH. Developmental programming of early brain and behavior development and mental health: a conceptual framework. Dev Med Child Neurol. 2011; 53, 1923.
31.Waddington, C. Organisers and Genes, 1940. Cambridge University Press: Cambridge, UK.
32.Van Speybroeck, L. From epigenesis to epigenetics. The case of C.H. Waddington. Ann N Y Acad Sci. 2002; 981, 6181.
33.Bird, A. Perceptions of epigenetics. Nature. 2007; 447, 396398.
34.World Health Organization. Promoting optimal fetal development: report of a technical consultation. Retrieved 19 April 2012 from
35.Waterland, RA, Jirtle, RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003; 23, 52935300.
36.Lillycrop, K, Phillips, E, Jackson, A, Hanson, M, Burdge, G. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005; 135, 13821386.
37.Deal, RB, Henikoff, JG, Henikoff, S. Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones. Science. 2010; 328, 11611164.
38.Lester, BM, Tronick, E, Nestler, E, et al. Behavioral epigenetics. Ann N Y Acad Sci. 2011; 1226, 1433.
39.Oberlander, TF, Weinberg, J, Papsdorf, M, et al. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008; 3, 97106.
40.Essex, MJ, Thomas Boyce, W, Hertzman, C, et al. Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence. Child Dev. 2011. Epub, doi:10.1111/j.1467-8624.2011.01641.x
41.Lester, B, Padbury, J. The third pathophysiology of prenatal cocaine exposure. Special Issue Dev Neurosci. 2009; 31, 2335.
42.Marsit, CJ, Maccani, MA, Padbury, JF, Lester, BM. Placental 11-beta hydroxysteroid dehydrogenase methylation is associated with newborn growth and a measure of neurobehavioral outcome. PLoS One. 2012; 7, e33794.
43.Bromer, C, Marsit, C, Padbury, J, Lester, B. Genetic and epigenetic variation of the glucocorticoid receptor (NR3C1) in placenta and neurobehavior. Dev Psychobiol. 2004; 160, 854860.
44.Marsit, CJ, Lambertini, L, Maccani, MA, et al. Placenta-imprinted gene expression association of infant neurobehavior. J Pediatr. 2011.
45.Gitau, R, Cameron, A, Fisk, NM, Glover, V. Fetal exposure to maternal cortisol. Lancet. 1998; 352, 707708.
46.Matthews, S. Early programming of the hypothalamo–pituitary–adrenal axis. Trends Endocrinol Metab. 2002; 13, 373380.
47.Padbury, JF, Martinez, AM. Sympathoadrenal system activity at birth: integration of postnatal adaptation. Semin Perinatol. 1988; 12, 163172.
48.Matthews, S. Antenatal glucocorticoids and the developing brain: mechanisms of action. Semin Neonatal. 2001; 6, 309317.
49.Slone-Wilcoxon, J, Redei, EE. Maternal-fetal glucocorticoid milieu programs hypothalamic–pituitary–thyroid function of adult offspring. Endocrinology. 2004; 145, 40684072.
50.Slotkin, TA, Orband-Miller, L, Queen, KL, Whitmore, WL, Seidler, FJ. Effects of prenatal nicotine exposure on biochemical development of rat brain regions: maternal drug infusions via osmotic minipumps. J Pharmacol Exp Ther. 1987; 240, 602611.
51.Williams, MT, Hennessy, MB, Davis, HN. Stress during pregnancy alters rat offspring morphology and ultrasonic vocalizations. Physiol Behav. 1998; 63, 337343.
52.Haussmann, MF, Carroll, JA, Weesner, GD, et al. Administration of ACTH to restrained, pregnant sows alters their pigs’ hypothalamic–pituitary–adrenal (HPA) axis. J Anim Sci. 2000; 78, 23992411.
53.Griffin, WC, Skinner, HD, Salm, AK, Birkle, DL. Mild prenatal stress in rats is associated with enhanced conditioned fear. Physiol Behav. 2003; 79, 209215.
54.French, NP, Hagan, R, Evans, SF, Mullan, A, Newnham, JP. Repeated antenatal corticosteroids: effects on cerebral palsy and childhood behavior. Am J Obstet Gynecol. 2004; 190, 588595.
55.Lou, H, Hansen, C, Nordentoft, M, et al.Prenatal stressors of human life affect fetal brain development. Dev Med Child Neurol. 1994; 36, 826832.
56.Rieger, M, Pirke, KM, Buske-Kirschbaum, A, et al. Influence of stress during pregnancy on HPA activity and neonatal behavior. Ann N Y Acad Sci. 2004; 1032, 228230.
57.Van den Bergh, BRH. The influence of maternal emotions during pregnancy on fetal and neonatal behavior. J Prenat Perinat Psychol Health. 1990; 5, 119130.
58.Van den Bergh, BRH. Maternal emotions during pregnancy and fetal and neonatal behavior. In Fetal Behavior: Developmental and Perinatal Aspects (ed. Nijhuis J), 1992; pp. 157178. Oxford University Press: Oxford, UK.
59.Van den Bergh, BRH, Mulder, EJH, Mennesa, M, Glover, V. Antenatal maternal anxiety and stress and neurobehavioral development of the fetus and child: links and possible mechanisms: a review. Neurosci Biobehav Rev. 2005; 29, 237258.
60.Van den Bergh, BRH, Van Calster, B, Smits, T, Van Huffel, S, Lagae, L. Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: a prospective study on the fetal origins of depressed mood. Neuropsychopharmacology. 2008; 33, 536545.
61.Lester, BM, Lagasse, LL, Shankaran, S, et al. Prenatal cocaine exposure related to cortisol stress reactivity in 11-year-old children. J Pediatr. 2010; 157, 288295 e1.
62.Bauer, CR, Lambert, BL, Bann, CM, et al. Long-term impact of maternal substance use during pregnancy and extrauterine environmental adversity: stress hormone levels of preadolescent children. Pediatr Res. 2011; 70, 213219.
63.Fisher, P, Kim, H, Bruce, J, Pears, K. Cumulative effects of prenatal substance exposure and early adversity on foster children's HPA axis reactivity during a psychosocial stressor. Int J Behav Dev. 2011; 36, 2935.
64.Barbazanges, A, Piazza, PV, Le Moal, M, Maccari, S. Maternal glucocorticoid secretion mediates long-term effects of prenatal stress. J Neurosci. 1996; 16, 39433949.
65.Henry, C, Kabbaj, M, Simon, H, Le Moal, M, Maccari, S. Prenatal stress increases the hypothalamo–pituitary–adrenal axis response in young and adult rats. J Neuroendocrinol. 1994; 6, 341345.
66.Henry, C, Kabbaj, M, Simon, H, LeMoal, M, Maccari, S. Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress induced corticosterone secretion. J Neuroendocrinol. 1994; 6, 341345.
67.Maccari, S, Piazza, PV, Kabbaj, M, et al.Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress. J Neurosci. 1995; 15(Pt 1), 110116.
68.Vallee, M, Mayo, W, Dellu, F, et al.Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion. J Neurosci. 1997; 17, 26262636.
69.Fride, E, Dan, Y, Feldon, J, Halevy, G, Weinstock, M. Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats. Physiol Behav. 1986; 37, 681687.
70.Poltyrev, T, Keshet, GI, Kay, G, Weinstock, M. Role of experimental conditions in determining differences in exploratory behavior of prenatally stressed rats. Dev Psychobiol. 1996; 29, 453462.
71.Wakshlak, A, Weinstock, M. Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress. Physiol Behav. 1990; 48, 289292.
72.Takahashi, LK, Haglin, C, Kalin, NH. Prenatal stress potentiates stress-induced behavior and reduces the propensity to play in juvenile rats. Physiol Behav. 1992; 51, 319323.
73.Takahashi, LK, Turner, JG, Kalin, NH. Prenatal stress alters brain catecholaminergic activity and potentiates stress-induced behavior in adult rats. Brain Res. 1992; 574, 131137.
74.Lambert, KG, Kinsley, CH, Jones, HE, et al.Prenatal stress attenuates ulceration in the activity stress paradigm. Physiol Behav. 1995; 57, 989994.
75.Weller, A, Glaubman, H, Yehuda, S, Caspy, T, Ben-Uria, Y. Acute and repeated gestational stress affect offspring learning and activity in rats. Physiol Behav. 1988; 43, 139143.
76.Hayashi, A, Nagaoka, M, Yamada, K, et al. Maternal stress induces synaptic loss and developmental disabilities of offspring. Int J Dev Neurosci. 1998; 16, 209216.
77.Szuran, T, Zimmermann, E, Welzl, H. Water maze performance and hippocampal weight of prenatally stressed rats. Behav Brain Res. 1994; 65, 153155.
78.Vallee, M, MacCari, S, Dellu, F, et al.Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat. Eur J Neurosci. 1999; 11, 29062916.
79.Meaney, M, Seckl, J. Glucocorticoid programming. Ann N Y Acad Sci. 2004; 1032, 6384.
80.Roughton, EC, Schneider, ML, Bromley, LJ, Coe, CL. Maternal endocrine activation during pregnancy alters neurobehavioral state in primate infants. Am J Occup Ther. 1998; 52, 9098.
81.Schneider, ML, Moore, CF, Kraemer, GW. Moderate level alcohol during pregnancy, prenatal stress, or both and limbic–hypothalamic–pituitary–adrenocortical axis response to stress in rhesus monkeys. Child Dev. 2004; 75, 96109.
82.Schneider, ML. Prenatal stress exposure alters postnatal behavioral expression under conditions of novelty challenge in rhesus monkey infants. Dev Psychobiol. 1992; 25, 529540.
83.McEwen, BS. Glucocorticoid–biogenic amine interactions in relation to mood and behavior. Biochem Pharmacol. 1987; 36, 17551763.
84.Maes, M, Meltzer, HY, D'Hondt, P, Cosyns, P, Blockx, P. Effects of serotonin precursors on the negative feedback effects of glucocorticoids on hypothalamic–pituitary–adrenal axis function in depression. Psychoneuroendocrinology. 1995; 20, 149167.
85.Meador-Woodruff, JH, Greden, JF, Grunhaus, L, Haskett, RF. Severity of depression and hypothalamic–pituitary–adrenal axis dysregulation: identification of contributing factors. Acta Psychiatr Scand. 1990; 81, 364371.
86.Nemeroff, CB, Widerlov, E, Bissette, G, et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science. 1984; 226, 13421344.
87.van Praag, H. Depression. Lancet. 1982; 8310, 12591264.
88.Wadhwa, PD, Garite, TJ, Porto, M, et al. Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: a prospective investigation. Am J Obstet Gynecol. 2004; 191, 10631069.
89.Wadhwa, PD, Sandman, CA, Garite, TJ. The neurobiology of stress in human pregnancy: implications for prematurity and development of the fetal central nervous system. Prog Brain Res. 2001; 133, 131142.
90.Kajantie, E, Raikkonen, K. Early life predictors of the physiological stress response later in life. Neurosci Biobehav Rev. 2010; 35, 2332.
91.van Os, J, Selten, J. Prenatal exposure to maternal stress and subsequent schizophrenia. Br J Psychiatry. 1998; 172, 324326.
92.Field, T. Stress and coping from pregnancy through the postnatal period. In Life-Span Developmental Psychology: Perspectives on Stress and Coping (ed. Cummings E), 1991; pp. 4559. Lawrence Erlbaum Associates: Hillsdale, NJ, USA.
93.Huizink, AC, Robles de Medina, PG, Mulder, EJ, Visser, GH, Buitelaar, JK. Stress during pregnancy is associated with developmental outcome in infancy. J Child Psychol Psychiatry. 2003; 44, 810818.
94.Levy-Shiff, R, Dimitrovsky, L, Shulman, S, Har-Even, D. Cognitive appraisals, coping strategies, and support resources as correlates of parenting and infant development. Dev Psychol. 1998; 34, 14171427.
95.Meijer, A. Child psychiatric sequelae of maternal war stress. Acta Psychiatr Scand. 1985; 72, 505511.
96.Stott, DH. Follow-up study from birth of the effects of prenatal stresses. Dev Med Child Neurol. 1973; 15, 770787.
97.Ward, AJ. Prenatal stress and childhood psychopathology. Child Psychiatry Hum Dev. 1991; 22, 97110.
98.DePietro, J. The role of prenatal maternal stress in child development. Curr Dir Psychol Sci. 2004; 13, 7174.
99.Bremner, JD, Randall, P, Vermetten, E, et al.Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse – a preliminary report. Biol Psychiatry. 1997; 41, 2332.
100.McEwen, BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998; 338, 171179.
101.McEwen, BS. Early life influences on life-long patterns of behavior and health. Ment Retard Dev Disabil Res Rev. 2003; 9, 149154.
102.Felitti, V, Anda, R, Nordenberg, D, et al.The relationship of adult health status to childhood abuse and household dysfunction. J Prev Med. 1998; 14, 42454258.
103.Meyer, JS. Biochemical effects of corticosteroids on neural tissues. Physiol Rev. 1985; 65, 9461020.
104.Lopez Bernal, A, Craft, IL. Corticosteroid metabolism in vitro by human placenta, fetal membranes and decidua in early and late gestation. Placenta. 1981; 2, 279285.
105.Benediktsson, R, Lindsay, RS, Noble, J, Seckl, JR, Edwards, CR. Glucocorticoid exposure in utero: new model for adult hypertension. Lancet. 1993; 341, 339341.
106.McTernan, CL, Draper, N, Nicholson, H, et al.Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms. J Clin Endocrinol Metab. 2001; 86, 49794983.
107.Murphy, VE, Zakar, T, Smith, R, et al.Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma. J Clin Endocrinol Metab. 2002; 87, 16601668.
108.Shams, M, Kilby, MD, Somerset, DA, et al.11beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction. Hum Reprod. 1998; 13, 799804.
109.Stewart, P, Roberson, F, Mason, J. Type 2 11-hydroxysteroid dehydrogenase messenger RNA and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal steroidogenesis. J Clin Endocrinol Metab. 1995; 80, 885890.
110.Holmes, MC, Abrahamsen, CT, French, KL, et al.The mother or the fetus? 11beta-hydroxysteroid dehydrogenase type 2 null mice provide evidence for direct fetal programming of behavior by endogenous glucocorticoids. J Neurosci. 2006; 26, 38403844.
111.Dave-Sharma, S, Wilson, R, Harbison, M. Extensive personal experience: examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1998; 83, 22442254.
112.Seckl, JR, Cleasby, M, Nyirenda, MJ. Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programming. Kidney Int. 2000; 57, 14121417.
113.Edwards, CR, Benediktsson, R, Lindsay, RS, Seckl, JR. Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet. 1993; 341, 355357.
114.Seckl, JR. Glucocorticoids, feto-placental 11 beta-hydroxysteroid dehydrogenase type 2, and the early life origins of adult disease. Steroids. 1997; 62, 8994.
115.Bohn, MC. Granule cell genesis in the hippocampus of rats treated neonatally with hydrocortisone. Neuroscience. 1980; 5, 20032012.
116.Gould, E, Woolley, CS, Cameron, HA, Daniels, DC, McEwen, BS. Adrenal steroids regulate postnatal development of the rat dentate gyrus: II. Effects of glucocorticoids and mineralocorticoids on cell birth. J Comp Neurol. 1991; 313, 486493.
117.Gould, E, Woolley, CS, McEwen, BS. Adrenal steroids regulate postnatal development of the rat dentate gyrus: I. Effects of glucocorticoids on cell death. J Comp Neurol. 1991; 313, 479485.
118.Sarkar, S, Tsai, S, Nguyen, T, Plevyak, M, Padbury, J. Inhibition of placental 11β-hydroxysteroid dehydrogenase type 2 by catecholamines via α-adrenergic signaling. Am J Physiol Regul Integr Comp Physiol. 2001; 281, R1966R1974.
119.Bottalico, B, Larsson, I, Brodszki, J, et al.Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies. Placenta. 2004; 25, 518529.
120.Bzoskie, L, Yen, J, Tseng, YT, et al.Human placental norepinephrine transporter mRNA: expression and correlation with fetal condition at birth. Placenta. 1997; 18, 205210.
121.Alikhani-Koopaei, R, Fouladkou, F, Frey, FJ, Frey, BM. Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression. J Clin Invest. 2004; 114, 11461157.
122.Friso, S, Pizzolo, F, Choi, SW, et al.Epigenetic control of 11 beta-hydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension. Atherosclerosis. 2008; 199, 323327.
123.Alikhani-Koupaei, R, Fouladkou, F, Fustier, P, et al.Identification of polymorphisms in the human 11beta hydroxysteroid dehydrogenase type 2 gene promoter: functional characterization and relevance for salt sensitivity. FASEB J. 2007; 21, 111.
124.Zanchi, N, Filho, M, Felitti, V, et al.Glucocorticoids: extensive physiological actions modulated through multiple mechanisms of gene regulation. J Cell Physiol. 2010; 224, 311315.
125.Yudt, MR, Cidlowski, JA. The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Mol Endocrinol. 2002; 16, 17191726.
126.Johnson, RF, Rennie, N, Murphy, V, et al.Expression of glucocorticoid receptor messenger ribonucleic acid transcripts in the human placenta at term. J Clin Endocrinol Metab. 2008; 93, 48874893.
127.Meaney, MJ, Szyf, M. Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci. 2005; 28, 456463.
128.Weaver, IC, Cervoni, N, Champagne, FA, et al.. Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7, 847854.
129.Liu, D, Diorio, J, Day, JC, Francis, DD, Meaney, MJ. Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci. 2000; 3, 799806.
130.Mark, PJ, Augustus, S, Lewis, JL, Hewitt, DP, Waddell, BJ. Changes in the placental glucocorticoid barrier during rat pregnancy: impact on placental corticosterone levels and regulation by progesterone. Biol Reprod. 2009; 80, 12091215.
131.Yiallourides, M, Sebert, SP, Wilson, V, et al.The differential effects of the timing of maternal nutrient restriction in the ovine placenta on glucocorticoid sensitivity, uncoupling protein 2, peroxisome proliferator-activated receptor-gamma and cell proliferation. Reproduction. 2009; 138, 601608.
132.Filiberto, AC, Maccani, MA, Koestler, D, et al.Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta. Epigenetics. 2011; 6, 566572.
133.Lester, BM, Tronick, EZ. The Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). Pediatrics (Supplement). 2004; 113, 631699.
134.El-Dib, M, Massaro, AN, Glass, P, Aly, H. Neurobehavioral assessment as a predictor of neurodevelopmental outcome in preterm infants. J Perinatol. 2011; 32, 299303.
135.Stephens, BE, Liu, J, Lester, B, et al.Neurobehavioral assessment predicts motor outcome in preterm infants. J Pediatr. 2010; 156, 366371.
136.Liu, J, Bann, C, Lester, B, et al.Neonatal neurobehavior predicts medical and behavioral outcome. Pediatrics. 2010; 125, e90e98.
137.Houseman, EA, Christensen, BC, Yeh, RF, et al.Model-based clustering of DNA methylation array data: a recursive-partitioning algorithm for high-dimensional data arising as a mixture of beta distributions. BMC Bioinformatics. 2008; 9 365.
138.Calkins, S, Hill, A. Caregiver influences on emerging emotion regulation: biological and environmental transactions in early development. In Handbook of Emotion Regulation (ed. Gross J), 2007; pp. 229248. The Guilford Press: New York, NY, USA.
139.Cohn, JF, Tronick, E. Specificity of infants’ response to mothers’ affective behavior. J Am Acad Child Adolesc Psychiatry. 1989; 28, 242248.
140.Tronick, E. The neurobehavioral and social-emotional development of infants and children, 2007. W.W. Norton & Company: New York, NY, USA.
141.Fracasso, M, Lamb, M, Scholmerich, A, Leyendecker, B. The ecology of mother–infant interaction in Euroamerican and immigrant central American families living in the United States. Int J Behav Dev. 1997; 20, 207218.
142.Chess, S, Thomas, A. Temperament and the concept of goodness of fit. In Explorations in Temperament (eds. Strelau J, Angleitner A), 1991, 15–28. Plenum: New York.
143.Lester, B, Boukydis, C, Garcia-Coll, C, et al.Developmental outcome as a function of the goodness of fit between the infant's cry characteristics and the mother's perception of her infant's cry. Pediatrics. 1995; 95, 516521.
144.Maziade, M. Should adverse temperament matter to the clinician? An empirically based answer. In Temperament in Childhood (eds. Kohnstamm G, Bates JE, Rothbart M), 1989; pp. 263281. Wiley: New York, NY, USA.
145.Van den Boom, D. The influence of temperament and mothering on attachment and exploration: an experimental manipulation of sensitive responsiveness among lower-class mothers with irritable infants. Child Dev. 1994; 65, 14591477.
146.Spangler, G, Grossmann, KE. Biobehavioral organization in securely and insecurely attached infants. Child Dev. 1993; 64, 14391450.
147.Gunnar, M. Psychoendocrine study of temperament and stress in early childhood: expanding current models. In Temperament: Individual Differences at the Interface of Biology and Behavior (eds. Bates J, Wachs TD), 1994; pp. 175198. American Psychological Association Press: New York.
148.Haley, DW, Stansbury, K. Infant stress and parent responsiveness: regulation of physiology and behavior during still-face and reunion. Child Dev. 2003; 74, 15341546.
149.Harwood, K, McLean, N, Durkin, K. First-time mothers’ expectations of parenthood: What happens when optimistic expectations are not matched by later experiences? Dev Psychol. 2007; 43, 112.
150.Hofer, MA. Evolutionary basis of adaptation in resilience and vulnerability: response to Cicchetti and Blender. Ann N Y Acad Sci. 2006; 1094, 259262.
151.Carroll, S. Endless Forms Most Beautiful: The New Science of Evo-Devo, 2005. W.W. Norton & Company: New York.
152.Cameron, NM, Champagne, FA, Parent, C, et al.The programming of individual differences in defensive responses and reproductive strategies in the rat through variations in maternal care. Neurosci Biobehav Rev. 2005; 29, 843865.
153.Boyce, WT, Ellis, BJ. Biological sensitivity to context: I. An evolutionary-developmental theory of the origins and functions of stress reactivity. Dev Psychopathol. 2005; 17, 271301.
154.Pluess, M, Belsky, J. Prenatal programming of postnatal plasticity? Dev Psychopathol. 2011; 23, 2938.
155.Harper, LV. Epigenetic inheritance and the intergenerational transfer of experience. Psychol Bull. 2005; 131, 340360.
156.Whitelaw, NC, Whitelaw, E. How lifetimes shape epigenotype within and across generations. Hum Mol Genet. 2006; 15 (Spec No. 2), R131R137.
157.Belsky, J. War, trauma and children's development: observations from a modern evolutionary perspective. Int J Behav Dev. 2008; 32, 260271.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed