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Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Review

Biological embedding of childhood adversity: from physiological mechanisms to clinical implications

Authors: Anne E. Berens, Sarah K. G. Jensen, Charles A. Nelson III

Published in: BMC Medicine | Issue 1/2017

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Abstract

Background

Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes “biologically embedded” in altered physiology across body systems. This review surveys evidence on such mechanisms and calls on researchers, clinicians, policymakers, and other practitioners to act upon evidence.

Observations

Childhood psychosocial adversity has wide-ranging effects on neural, endocrine, immune, and metabolic physiology. Molecular mechanisms broadly implicate disruption of central neural networks, neuroendocrine stress dysregulation, and chronic inflammation, among other changes. Physiological disruption predisposes individuals to common diseases across the life course.

Conclusions

Reviewed evidence has important implications for clinical practice, biomedical research, and work across other sectors relevant to public health and child wellbeing. Warranted changes include increased clinical screening for exposures among children and adults, scale-up of effective interventions, policy advocacy, and ongoing research to develop new evidence-based response strategies.
Literature
1.
go back to reference Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245–58.PubMedCrossRef Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245–58.PubMedCrossRef
2.
go back to reference Liu Y, Croft JB, Chapman DP, Perry GS, Greenlund KJ, Zhao G, Edwards VJ. Relationship between adverse childhood experiences and unemployment among adults from five U.S. states. Soc Psychiatry Psychiatr Epidemiol. 2013;48(3):357–69.PubMedCrossRef Liu Y, Croft JB, Chapman DP, Perry GS, Greenlund KJ, Zhao G, Edwards VJ. Relationship between adverse childhood experiences and unemployment among adults from five U.S. states. Soc Psychiatry Psychiatr Epidemiol. 2013;48(3):357–69.PubMedCrossRef
3.
go back to reference Danese A, Moffitt TE, Harrington H, Milne BJ, Polanczyk G, Pariante CM, et al. Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolesc Med. 2009;163(12):1135–43.PubMedPubMedCentralCrossRef Danese A, Moffitt TE, Harrington H, Milne BJ, Polanczyk G, Pariante CM, et al. Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolesc Med. 2009;163(12):1135–43.PubMedPubMedCentralCrossRef
4.
go back to reference Giovanelli A, Reynolds AJ, Mondi CF, Ou SR. Adverse childhood experiences and adult well-being in a low-income, urban cohort. Pediatrics. 2016;137(4):e20154016. doi:10.1542/peds.2015-4016. Giovanelli A, Reynolds AJ, Mondi CF, Ou SR. Adverse childhood experiences and adult well-being in a low-income, urban cohort. Pediatrics. 2016;137(4):e20154016. doi:10.​1542/​peds.​2015-4016.
5.
7.
go back to reference Kelly-Irving M, Mabile L, Grosclaude P, Lang T, Delpierre C. The embodiment of adverse childhood experiences and cancer development: potential biological mechanisms and pathways across the life course. Int J Public Health. 2013;58:3–11.PubMedCrossRef Kelly-Irving M, Mabile L, Grosclaude P, Lang T, Delpierre C. The embodiment of adverse childhood experiences and cancer development: potential biological mechanisms and pathways across the life course. Int J Public Health. 2013;58:3–11.PubMedCrossRef
8.
go back to reference Kelly-Irving M, Lepage B, Dedieu D, Bartley M, Blane D, Grosclaude P, Lang T, Delpierre C. Adverse childhood experiences and premature all-cause mortality. Eur J Epidemiol. 2013;28:1–14.CrossRef Kelly-Irving M, Lepage B, Dedieu D, Bartley M, Blane D, Grosclaude P, Lang T, Delpierre C. Adverse childhood experiences and premature all-cause mortality. Eur J Epidemiol. 2013;28:1–14.CrossRef
9.
go back to reference Barboza Solís C, Kelly-Irving M, Fantin R, Darnaudéry M, Torrisani J, Lang T, Delpierre C. Adverse childhood experiences and physiological wear-and-tear in midlife: findings from the 1958 British birth cohort. Proc Natl Acad Sci U S A. 2015;112(7):E738–46.PubMedPubMedCentralCrossRef Barboza Solís C, Kelly-Irving M, Fantin R, Darnaudéry M, Torrisani J, Lang T, Delpierre C. Adverse childhood experiences and physiological wear-and-tear in midlife: findings from the 1958 British birth cohort. Proc Natl Acad Sci U S A. 2015;112(7):E738–46.PubMedPubMedCentralCrossRef
10.
11.
go back to reference Graignic-Philippe R, Dayan J, Chokron S, Jacquet AY, Tordjman S. Effects of prenatal stress on fetal and child development: a critical literature review. Neurosci Biobehav Rev. 2014;43:137–62.PubMedCrossRef Graignic-Philippe R, Dayan J, Chokron S, Jacquet AY, Tordjman S. Effects of prenatal stress on fetal and child development: a critical literature review. Neurosci Biobehav Rev. 2014;43:137–62.PubMedCrossRef
12.
go back to reference Martikainen P, Bartley M, Lahelma E. Psychosocial determinants of health in social epidemiology. Int J Epidemiol. 2002;31(6):1091–3.PubMedCrossRef Martikainen P, Bartley M, Lahelma E. Psychosocial determinants of health in social epidemiology. Int J Epidemiol. 2002;31(6):1091–3.PubMedCrossRef
13.
go back to reference Hillis S, Mercy J, Amobi A, Kress H. Global prevalence of past-year violence against children: a systematic review and minimum estimates. Pediatrics. 2016;137(3):1–13.CrossRef Hillis S, Mercy J, Amobi A, Kress H. Global prevalence of past-year violence against children: a systematic review and minimum estimates. Pediatrics. 2016;137(3):1–13.CrossRef
14.
go back to reference Moussavi S, Somnath S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007;370(9590):851–8.PubMedCrossRef Moussavi S, Somnath S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007;370(9590):851–8.PubMedCrossRef
16.
go back to reference Fox SE, Levitt P, Nelson CA. How the timing and quality of early experiences influence the development of brain architecture. Child Dev. 2010;81:28–40.PubMedPubMedCentralCrossRef Fox SE, Levitt P, Nelson CA. How the timing and quality of early experiences influence the development of brain architecture. Child Dev. 2010;81:28–40.PubMedPubMedCentralCrossRef
17.
go back to reference Avitsur R, Levy S, Goren N, Grinshpahet R. Early adversity, immunity and infectious disease. Stress. 2015;18(3):289–96.PubMedCrossRef Avitsur R, Levy S, Goren N, Grinshpahet R. Early adversity, immunity and infectious disease. Stress. 2015;18(3):289–96.PubMedCrossRef
18.
go back to reference Miller GE, Chen E, Parker KJ. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol Bull. 2011;137:959–97.PubMedPubMedCentralCrossRef Miller GE, Chen E, Parker KJ. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychol Bull. 2011;137:959–97.PubMedPubMedCentralCrossRef
19.
go back to reference Essex MJ, Boyce WT, Hertzman C, Lam LL, Armstrong JM, Neumann SM, Kobor MS. Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence. Child Dev. 2013;84:58–75.PubMedCrossRef Essex MJ, Boyce WT, Hertzman C, Lam LL, Armstrong JM, Neumann SM, Kobor MS. Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence. Child Dev. 2013;84:58–75.PubMedCrossRef
20.
go back to reference Reuben A, Moffitt TE, Caspi A, Belsky DW, Harrington H, Schroeder F, et al. Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health. J Child Psychol Psychiatry. 2016;57(10):1103–12.PubMedCrossRef Reuben A, Moffitt TE, Caspi A, Belsky DW, Harrington H, Schroeder F, et al. Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health. J Child Psychol Psychiatry. 2016;57(10):1103–12.PubMedCrossRef
21.
go back to reference Bick J, Nelson CA. Early adverse experiences and the developing brain. Neuropsychopharmacology. 2016;41:177–96.PubMedCrossRef Bick J, Nelson CA. Early adverse experiences and the developing brain. Neuropsychopharmacology. 2016;41:177–96.PubMedCrossRef
22.
go back to reference Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, et al. A structural MRI study of human brain development from birth to 2 years. J Neurosci. 2008;28(47):12176.PubMedPubMedCentralCrossRef Knickmeyer RC, Gouttard S, Kang C, Evans D, Wilber K, Smith JK, et al. A structural MRI study of human brain development from birth to 2 years. J Neurosci. 2008;28(47):12176.PubMedPubMedCentralCrossRef
23.
go back to reference Deoni SCL, Dean DC, O'Muircheartaigh J, Dirks H, Jerskey BA. Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping. Neuroimage. 2012;63(3):1038–53.PubMedPubMedCentralCrossRef Deoni SCL, Dean DC, O'Muircheartaigh J, Dirks H, Jerskey BA. Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping. Neuroimage. 2012;63(3):1038–53.PubMedPubMedCentralCrossRef
25.
go back to reference Nemeroff CB. Paradise lost: the neurobiological and clinical consequences of child abuse and neglect. Neuron. 2016;89:892–909.PubMedCrossRef Nemeroff CB. Paradise lost: the neurobiological and clinical consequences of child abuse and neglect. Neuron. 2016;89:892–909.PubMedCrossRef
26.
go back to reference McEwen BS, Nasca C, Gray JD. Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology. 2016;41:3–23.PubMedCrossRef McEwen BS, Nasca C, Gray JD. Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology. 2016;41:3–23.PubMedCrossRef
27.
go back to reference Tottenham N, Sheridan MA. A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing. Front Hum Neurosci. 2010;3:68.PubMedPubMedCentral Tottenham N, Sheridan MA. A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing. Front Hum Neurosci. 2010;3:68.PubMedPubMedCentral
28.
go back to reference Uno H, Eisele S, Sakai A, Shelton S, Baker E, DeJesus O, Holden J. Neurotoxicity of glucocorticoids in the primate brain. Horm Behav. 1994;28(4):336–48.PubMedCrossRef Uno H, Eisele S, Sakai A, Shelton S, Baker E, DeJesus O, Holden J. Neurotoxicity of glucocorticoids in the primate brain. Horm Behav. 1994;28(4):336–48.PubMedCrossRef
29.
go back to reference Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav. 2012;106:29–39.PubMedCrossRef Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav. 2012;106:29–39.PubMedCrossRef
30.
go back to reference Do KQ, Cuenod M, Hensch TK. Targeting oxidative stress and aberrant critical period plasticity in the developmental trajectory to schizophrenia. Schizophr Bull. 2015;41(4):835–46.PubMedPubMedCentralCrossRef Do KQ, Cuenod M, Hensch TK. Targeting oxidative stress and aberrant critical period plasticity in the developmental trajectory to schizophrenia. Schizophr Bull. 2015;41(4):835–46.PubMedPubMedCentralCrossRef
31.
go back to reference Sarro EC, Sullivan RM, Barr G. Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA. Neurosci. 2014;258:147–61.CrossRef Sarro EC, Sullivan RM, Barr G. Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA. Neurosci. 2014;258:147–61.CrossRef
32.
go back to reference Berens AE, Nelson CA. The science of early adversity: is there a role for large institutions in the care of vulnerable children? Lancet. 2015;386(9991):388–98.PubMedCrossRef Berens AE, Nelson CA. The science of early adversity: is there a role for large institutions in the care of vulnerable children? Lancet. 2015;386(9991):388–98.PubMedCrossRef
33.
go back to reference Knudsen EI. Sensitive periods in the development of the brain and behavior. J Cogn Neurosci. 2004;16:1412–25.PubMedCrossRef Knudsen EI. Sensitive periods in the development of the brain and behavior. J Cogn Neurosci. 2004;16:1412–25.PubMedCrossRef
34.
go back to reference McLaughlin KA, Sheridan MA, Winter W, Fox NA, Zeanah CH, Nelson CA. Widespread reductions in cortical thickness following severe early-life deprivation: a neurodevelopmental pathway to attention-deficit/hyperactivity disorder. Biol Psychiatry. 2014;76(8):629–38.PubMedCrossRef McLaughlin KA, Sheridan MA, Winter W, Fox NA, Zeanah CH, Nelson CA. Widespread reductions in cortical thickness following severe early-life deprivation: a neurodevelopmental pathway to attention-deficit/hyperactivity disorder. Biol Psychiatry. 2014;76(8):629–38.PubMedCrossRef
35.
go back to reference McLaughlin KA, Sheridan MA, Lambert HK. Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience. Neurosci Biobehav Rev. 2014;47:578–91.PubMedPubMedCentralCrossRef McLaughlin KA, Sheridan MA, Lambert HK. Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience. Neurosci Biobehav Rev. 2014;47:578–91.PubMedPubMedCentralCrossRef
36.
go back to reference Doom JR, Gunnar MR. Stress in infancy and early childhood: effects on development. In: Wright JD, Ed. International Encyclopedia of the Social & Behavioral Sciences. Amsterdam: Elsevier Science & Technology; 2015. Vol. 23. pp. 577–82. Doom JR, Gunnar MR. Stress in infancy and early childhood: effects on development. In: Wright JD, Ed. International Encyclopedia of the Social & Behavioral Sciences. Amsterdam: Elsevier Science & Technology; 2015. Vol. 23. pp. 577–82.
37.
go back to reference Liston C, Gan WB. Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proc Natl Acad Sci U S A. 2011;108(38):16074–9.PubMedPubMedCentralCrossRef Liston C, Gan WB. Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proc Natl Acad Sci U S A. 2011;108(38):16074–9.PubMedPubMedCentralCrossRef
38.
go back to reference Jensen SK, Dickie EW, Schwartz DH, et al. Effect of early adversity and childhood internalizing symptoms on brain structure in young men. JAMA Pediatr. 2015;169(10):938–46.PubMedPubMedCentralCrossRef Jensen SK, Dickie EW, Schwartz DH, et al. Effect of early adversity and childhood internalizing symptoms on brain structure in young men. JAMA Pediatr. 2015;169(10):938–46.PubMedPubMedCentralCrossRef
39.
go back to reference Hensch TK, Bilimoria PM. Re-opening windows: manipulating critical periods for brain development. Cerebrum. 2012;2012:11.PubMedPubMedCentral Hensch TK, Bilimoria PM. Re-opening windows: manipulating critical periods for brain development. Cerebrum. 2012;2012:11.PubMedPubMedCentral
40.
go back to reference Nusslock R, Miller GE. Early-life adversity and physical and emotional health across the lifespan: a neuroimmune network hypothesis. Biol Psychiatry. 2016;80:23–32.PubMedCrossRef Nusslock R, Miller GE. Early-life adversity and physical and emotional health across the lifespan: a neuroimmune network hypothesis. Biol Psychiatry. 2016;80:23–32.PubMedCrossRef
41.
go back to reference Dillon DG, Holmes AJ, Birk JL, Brooks N, Lyons-Ruth K, Pizzagalli DA. Childhood adversity is associated with left basal ganglia dysfunction during reward anticipation in adulthood. Biol Psychiatry. 2009;66(3):206–13.PubMedPubMedCentralCrossRef Dillon DG, Holmes AJ, Birk JL, Brooks N, Lyons-Ruth K, Pizzagalli DA. Childhood adversity is associated with left basal ganglia dysfunction during reward anticipation in adulthood. Biol Psychiatry. 2009;66(3):206–13.PubMedPubMedCentralCrossRef
42.
go back to reference Tawakol A, Ishai A, Takx RAP, et al. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017;389(10071):834–45.PubMedCrossRef Tawakol A, Ishai A, Takx RAP, et al. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017;389(10071):834–45.PubMedCrossRef
43.
go back to reference Meaney MJ. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci. 2001;24:1161–92.PubMedCrossRef Meaney MJ. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci. 2001;24:1161–92.PubMedCrossRef
44.
go back to reference Lovallo WR. Early life adversity reduces stress reactivity and enhances impulsive behavior: Implications for health behaviors. Int J Psychophysiol. 2013;90:8–16.PubMedCrossRef Lovallo WR. Early life adversity reduces stress reactivity and enhances impulsive behavior: Implications for health behaviors. Int J Psychophysiol. 2013;90:8–16.PubMedCrossRef
45.
go back to reference Rao U, Hammen C, Ortiz LR, Chen L, Poland RE. Effects of early and recent adverse experiences on adrenal response to psychosocial stress in depressed adolescents. Biol Psychiatry. 2008;64:521–6.PubMedPubMedCentralCrossRef Rao U, Hammen C, Ortiz LR, Chen L, Poland RE. Effects of early and recent adverse experiences on adrenal response to psychosocial stress in depressed adolescents. Biol Psychiatry. 2008;64:521–6.PubMedPubMedCentralCrossRef
46.
go back to reference Tyrka AR, Price LH, Gelernter J, Schepker C, Anderson GM, Carpenter LL. Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: effects on hypothalamic-pituitary-adrenal axis reactivity. Biol Psyc. 2009;66:681–5.CrossRef Tyrka AR, Price LH, Gelernter J, Schepker C, Anderson GM, Carpenter LL. Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: effects on hypothalamic-pituitary-adrenal axis reactivity. Biol Psyc. 2009;66:681–5.CrossRef
47.
go back to reference Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, et al. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA. 2000;284(5):592–7.PubMedCrossRef Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, et al. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA. 2000;284(5):592–7.PubMedCrossRef
48.
go back to reference Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. 2003;160(9):1554–65.PubMedCrossRef Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. 2003;160(9):1554–65.PubMedCrossRef
49.
go back to reference Antoni MH, Lutgendorf SK, Cole SW, Dhabhar FS, Sephton SE, McDonald PG, et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer. 2006;6(3):240–8.PubMedPubMedCentralCrossRef Antoni MH, Lutgendorf SK, Cole SW, Dhabhar FS, Sephton SE, McDonald PG, et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer. 2006;6(3):240–8.PubMedPubMedCentralCrossRef
51.
go back to reference Meaney MJ, Szyf M. Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci. 2005;28:456–63.PubMedCrossRef Meaney MJ, Szyf M. Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci. 2005;28:456–63.PubMedCrossRef
52.
go back to reference McGowan P, Szyf M. The epigenetics of social adversity in early life: Implications for mental health outcomes. Neurobiol Dis. 2010;39:66–72.PubMedCrossRef McGowan P, Szyf M. The epigenetics of social adversity in early life: Implications for mental health outcomes. Neurobiol Dis. 2010;39:66–72.PubMedCrossRef
53.
go back to reference Perroud N, Paoloni-Giacobino A, Prada P, Olie E, Salzmann A, Nicastro R, et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry. 2011;1(12), e59.PubMedPubMedCentralCrossRef Perroud N, Paoloni-Giacobino A, Prada P, Olie E, Salzmann A, Nicastro R, et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry. 2011;1(12), e59.PubMedPubMedCentralCrossRef
55.
go back to reference Alkon A, Wolff B, Boyce WT. Poverty, Stress, and Autonomic Reactivity. The Oxford Handbook of Poverty and Child Development. New York, NY: Oxford University Press; 2012. Alkon A, Wolff B, Boyce WT. Poverty, Stress, and Autonomic Reactivity. The Oxford Handbook of Poverty and Child Development. New York, NY: Oxford University Press; 2012.
56.
go back to reference El-Sheikh M, Kouros CD, Erath S, Cummings E, Keller P, Staton L. Marital Conflict and Children's Externalizing Behavior: Interactions between Parasympathetic and Sympathetic Nervous System Activity. Monographs of the Society for Research in Child Development Series. Wiley; 2009. El-Sheikh M, Kouros CD, Erath S, Cummings E, Keller P, Staton L. Marital Conflict and Children's Externalizing Behavior: Interactions between Parasympathetic and Sympathetic Nervous System Activity. Monographs of the Society for Research in Child Development Series. Wiley; 2009.
57.
go back to reference Gatt JM, Nemeroff CB, Dobson-Stone C, Paul RH, Bryant RA, Schofield PR, et al. Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol Psychiatry. 2009;14:681–95.PubMedCrossRef Gatt JM, Nemeroff CB, Dobson-Stone C, Paul RH, Bryant RA, Schofield PR, et al. Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol Psychiatry. 2009;14:681–95.PubMedCrossRef
58.
go back to reference Kanterman J, Sade-Feldman M, Baniyash M. New insights into chronic inflammation-induced immunosuppression. Semin Cancer Biol. 2012;22:307–18.PubMedCrossRef Kanterman J, Sade-Feldman M, Baniyash M. New insights into chronic inflammation-induced immunosuppression. Semin Cancer Biol. 2012;22:307–18.PubMedCrossRef
59.
go back to reference Fagundes CP, Glaser R, Kiecolt-Glaser JK. Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav Immun. 2013;27:8–12.PubMedCrossRef Fagundes CP, Glaser R, Kiecolt-Glaser JK. Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav Immun. 2013;27:8–12.PubMedCrossRef
60.
go back to reference Shirtcliff EA, Coe CL, Pollak SD. Early childhood stress is associated with elevated antibody levels to herpes simplex virus type 1. Proc Natl Acad Sci U S A. 2009;106(8):2963.PubMedPubMedCentralCrossRef Shirtcliff EA, Coe CL, Pollak SD. Early childhood stress is associated with elevated antibody levels to herpes simplex virus type 1. Proc Natl Acad Sci U S A. 2009;106(8):2963.PubMedPubMedCentralCrossRef
61.
go back to reference Slopen N, McLaughlin KA, Dunn EC, Koenen KC. Childhood adversity and cell-mediated immunity in young adulthood: does type and timing matter? Brain Behav Immun. 2013;28:63–71.PubMedCrossRef Slopen N, McLaughlin KA, Dunn EC, Koenen KC. Childhood adversity and cell-mediated immunity in young adulthood: does type and timing matter? Brain Behav Immun. 2013;28:63–71.PubMedCrossRef
62.
go back to reference Lemieux A, Coe CL, Carnes M. Symptom severity predicts degree of T cell activation in adult women following childhood maltreatment. Brain Behav Immun. 2008;22:994–1003.PubMedPubMedCentralCrossRef Lemieux A, Coe CL, Carnes M. Symptom severity predicts degree of T cell activation in adult women following childhood maltreatment. Brain Behav Immun. 2008;22:994–1003.PubMedPubMedCentralCrossRef
63.
go back to reference Miller GE, Chen E. Harsh family climate in early life presages the emergence of a proinflammatory phenotype in adolescence. Psychol Sci. 2010;21(6):848–56.PubMedPubMedCentralCrossRef Miller GE, Chen E. Harsh family climate in early life presages the emergence of a proinflammatory phenotype in adolescence. Psychol Sci. 2010;21(6):848–56.PubMedPubMedCentralCrossRef
64.
go back to reference Miller GE, Chen E, Fok AK, et al. Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc Natl Acad Sci U S A. 2009;106(34):14716–21.PubMedPubMedCentralCrossRef Miller GE, Chen E, Fok AK, et al. Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc Natl Acad Sci U S A. 2009;106(34):14716–21.PubMedPubMedCentralCrossRef
65.
go back to reference Powell ND, Sloan EK, Bailey MT, et al. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc Natl Acad Sci U S A. 2013;110(41):16574–9.PubMedPubMedCentralCrossRef Powell ND, Sloan EK, Bailey MT, et al. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc Natl Acad Sci U S A. 2013;110(41):16574–9.PubMedPubMedCentralCrossRef
66.
go back to reference Slopen N, Koenen KC, Kubzansky LD. Childhood adversity and immune and inflammatory biomarkers associated with cardiovascular risk in youth: a systematic review. Brain Behav Immun. 2012;26:239–50.PubMedCrossRef Slopen N, Koenen KC, Kubzansky LD. Childhood adversity and immune and inflammatory biomarkers associated with cardiovascular risk in youth: a systematic review. Brain Behav Immun. 2012;26:239–50.PubMedCrossRef
67.
go back to reference Baumeister D, Akhtar R, Ciufolini S, Pariante C, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Mol Psychiatry. 2016;21(5):642–9.PubMedCrossRef Baumeister D, Akhtar R, Ciufolini S, Pariante C, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Mol Psychiatry. 2016;21(5):642–9.PubMedCrossRef
68.
go back to reference Godbout JP, Glaser R. Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J Neuroimmune Pharmacol. 2006;1(4):421–7.PubMedCrossRef Godbout JP, Glaser R. Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J Neuroimmune Pharmacol. 2006;1(4):421–7.PubMedCrossRef
69.
go back to reference Thomas C, Hypponen E, Power C. Obesity and type 2 diabetes risk in midadult life: the role of childhood adversity. Pediatrics. 2008;121:e1240–9.PubMedCrossRef Thomas C, Hypponen E, Power C. Obesity and type 2 diabetes risk in midadult life: the role of childhood adversity. Pediatrics. 2008;121:e1240–9.PubMedCrossRef
70.
go back to reference Maniam J, Antoniadis C, Morris MJ. Early-life stress, HPA axis adaptation, and mechanisms contributing to later health outcomes. Front Endocrinol. 2014;5:73.CrossRef Maniam J, Antoniadis C, Morris MJ. Early-life stress, HPA axis adaptation, and mechanisms contributing to later health outcomes. Front Endocrinol. 2014;5:73.CrossRef
71.
go back to reference Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404:661–71.PubMed Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404:661–71.PubMed
72.
go back to reference Mason SM, Flint AJ, Field AE, Austin SB, Rich‐Edwards JW. Abuse victimization in childhood or adolescence and risk of food addiction in adult women. Obesity. 2013;21(12):E775–E81.PubMedPubMedCentralCrossRef Mason SM, Flint AJ, Field AE, Austin SB, Rich‐Edwards JW. Abuse victimization in childhood or adolescence and risk of food addiction in adult women. Obesity. 2013;21(12):E775–E81.PubMedPubMedCentralCrossRef
73.
go back to reference Moloney RD, Desbonnet L, Clarke G, Dinan TG, Cryan JF. The microbiome: stress, health and disease. Mamm Genome. 2014;25:49–74.PubMedCrossRef Moloney RD, Desbonnet L, Clarke G, Dinan TG, Cryan JF. The microbiome: stress, health and disease. Mamm Genome. 2014;25:49–74.PubMedCrossRef
74.
go back to reference O'Mahony SM, Clarke G, Dinan TG, Cryan JF. Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle? Neuroscience. 2017;342:37–54.PubMedCrossRef O'Mahony SM, Clarke G, Dinan TG, Cryan JF. Early-life adversity and brain development: Is the microbiome a missing piece of the puzzle? Neuroscience. 2017;342:37–54.PubMedCrossRef
75.
go back to reference Clarke G, O'Mahony SM, Dinan TG, Cryan JF. Priming for health: gut microbiota acquired in early life regulates physiology, brain and behaviour. Acta Paediatr. 2014;103:812–9.PubMedCrossRef Clarke G, O'Mahony SM, Dinan TG, Cryan JF. Priming for health: gut microbiota acquired in early life regulates physiology, brain and behaviour. Acta Paediatr. 2014;103:812–9.PubMedCrossRef
76.
go back to reference Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J Physiol. 2004;558(1):263–75.PubMedPubMedCentralCrossRef Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, et al. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J Physiol. 2004;558(1):263–75.PubMedPubMedCentralCrossRef
77.
78.
go back to reference Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13:701–12.PubMedCrossRef Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13:701–12.PubMedCrossRef
80.
go back to reference Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour: Epigenetic regulation of the gut–brain axis. Genes Brain Behav. 2014;13(1):69–86.PubMedCrossRef Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour: Epigenetic regulation of the gut–brain axis. Genes Brain Behav. 2014;13(1):69–86.PubMedCrossRef
81.
go back to reference O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho A, Quiggley EM, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009;65:263–7.PubMedCrossRef O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho A, Quiggley EM, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009;65:263–7.PubMedCrossRef
82.
go back to reference Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011;25:397–407.PubMedCrossRef Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011;25:397–407.PubMedCrossRef
83.
go back to reference Ganguly P, Brenhouse HC. Broken or maladaptive? Altered trajectories in neuroinflammation and behavior after early life adversity. Dev Cogn Neurosci. 2015;11:18–30.PubMedCrossRef Ganguly P, Brenhouse HC. Broken or maladaptive? Altered trajectories in neuroinflammation and behavior after early life adversity. Dev Cogn Neurosci. 2015;11:18–30.PubMedCrossRef
84.
go back to reference Hertzman C, Boyce T. How experience gets under the skin to create gradients in developmental health. Annu Rev Public Health. 2010;31:329–47.PubMedCrossRef Hertzman C, Boyce T. How experience gets under the skin to create gradients in developmental health. Annu Rev Public Health. 2010;31:329–47.PubMedCrossRef
85.
go back to reference Ellis BJ, Essex MJ, Boyce WT. Biological sensitivity to context: II. Empirical explorations of an evolutionary-developmental theory. Dev Psychopathol. 2005;17:303–28.PubMedCrossRef Ellis BJ, Essex MJ, Boyce WT. Biological sensitivity to context: II. Empirical explorations of an evolutionary-developmental theory. Dev Psychopathol. 2005;17:303–28.PubMedCrossRef
86.
go back to reference Lester BM, Masten AS, McEwen BS, editors. Resilience in Children. Boston: Blackwell Publications on behalf of the New York Academy of Sciences; 2006. Lester BM, Masten AS, McEwen BS, editors. Resilience in Children. Boston: Blackwell Publications on behalf of the New York Academy of Sciences; 2006.
87.
go back to reference Heim C, Binder EB. Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Exp Neurol. 2012;233:102–11.PubMedCrossRef Heim C, Binder EB. Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Exp Neurol. 2012;233:102–11.PubMedCrossRef
88.
go back to reference Fredericks CA, Drabant EM, Edge MD, Tillie JM, Hallmayer J, Ramel W, et al. Healthy young women with serotonin transporter SS polymorphism show a pro-inflammatory bias under resting and stress conditions. Brain Behave Immun. 2010;24(3):350–7.CrossRef Fredericks CA, Drabant EM, Edge MD, Tillie JM, Hallmayer J, Ramel W, et al. Healthy young women with serotonin transporter SS polymorphism show a pro-inflammatory bias under resting and stress conditions. Brain Behave Immun. 2010;24(3):350–7.CrossRef
89.
go back to reference Zhao J, Bremner JD, Goldberg J, Quyyumi AA, Vaccarino V. MAOA genotype, childhood trauma and subclinical atherosclerosis: a twin study. Psychosom Med. 2013;75(5):471–7.PubMedPubMedCentralCrossRef Zhao J, Bremner JD, Goldberg J, Quyyumi AA, Vaccarino V. MAOA genotype, childhood trauma and subclinical atherosclerosis: a twin study. Psychosom Med. 2013;75(5):471–7.PubMedPubMedCentralCrossRef
90.
go back to reference Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, Moffitt TE. MAOA, maltreatment, and gene-environment interaction predicting children's mental health: new evidence and a meta-analysis. Molec Psychiatry. 2006;11(10):903.CrossRef Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, Moffitt TE. MAOA, maltreatment, and gene-environment interaction predicting children's mental health: new evidence and a meta-analysis. Molec Psychiatry. 2006;11(10):903.CrossRef
91.
go back to reference Brummett BH, Boyle SH, Siegler IC, et al. Effects of environmental stress and gender on associations among symptoms of depression and the serotonin transporter gene linked polymorphic region (5-HTTLPR). Behav Genet. 2008;38(1):34–43.PubMedCrossRef Brummett BH, Boyle SH, Siegler IC, et al. Effects of environmental stress and gender on associations among symptoms of depression and the serotonin transporter gene linked polymorphic region (5-HTTLPR). Behav Genet. 2008;38(1):34–43.PubMedCrossRef
92.
go back to reference Evans GW, Kim P, Ting AH, Tesher HB, Shannis D. Cumulative risk, maternal responsiveness, and allostatic load among young adolescents. Dev Psychol. 2007;43(2):341–51.PubMedCrossRef Evans GW, Kim P, Ting AH, Tesher HB, Shannis D. Cumulative risk, maternal responsiveness, and allostatic load among young adolescents. Dev Psychol. 2007;43(2):341–51.PubMedCrossRef
93.
go back to reference Carroll JE, Gruenewald TL, Taylor SE, Janicki-Deverts D, Matthews KA, Seeman TE. Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study. Proc Natl Acad Sci U S A. 2013;110(42):17149–53.PubMedPubMedCentralCrossRef Carroll JE, Gruenewald TL, Taylor SE, Janicki-Deverts D, Matthews KA, Seeman TE. Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study. Proc Natl Acad Sci U S A. 2013;110(42):17149–53.PubMedPubMedCentralCrossRef
94.
go back to reference Chen E, Miller GE, Kobor MS, Cole SW. Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood. Mol Psychiatry. 2011;16(7):729–37.PubMedCrossRef Chen E, Miller GE, Kobor MS, Cole SW. Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood. Mol Psychiatry. 2011;16(7):729–37.PubMedCrossRef
95.
go back to reference Luecken LJ. Parental caring and loss during childhood and adult cortisol responses to stress. Psychol Health. 2000;15(6):841–51.CrossRef Luecken LJ. Parental caring and loss during childhood and adult cortisol responses to stress. Psychol Health. 2000;15(6):841–51.CrossRef
96.
go back to reference Brody GH, Yu T, Beach SR. Resilience to adversity and the early origins of disease. Dev Psychopathol. 2016;28:1347–65.PubMedCrossRef Brody GH, Yu T, Beach SR. Resilience to adversity and the early origins of disease. Dev Psychopathol. 2016;28:1347–65.PubMedCrossRef
97.
go back to reference Luby J, Belden A, Botteron K, Marrus N, Harms M, Babb C, et al. The effects of poverty on childhood brain development: the mediating effect of caregiving and stressful life events. JAMA Pediatr. 2013;167(12):1135–42.PubMedPubMedCentralCrossRef Luby J, Belden A, Botteron K, Marrus N, Harms M, Babb C, et al. The effects of poverty on childhood brain development: the mediating effect of caregiving and stressful life events. JAMA Pediatr. 2013;167(12):1135–42.PubMedPubMedCentralCrossRef
98.
go back to reference Miller GE, Brody GH, Yu T, Chen E. A family-oriented psychosocial intervention reduces inflammation in low-SES African American youth. Proc Natl Acad Sci U S A. 2014;111(31):11287–92.PubMedPubMedCentralCrossRef Miller GE, Brody GH, Yu T, Chen E. A family-oriented psychosocial intervention reduces inflammation in low-SES African American youth. Proc Natl Acad Sci U S A. 2014;111(31):11287–92.PubMedPubMedCentralCrossRef
99.
go back to reference Drury SS, Theall K, Gleason MM, Smyke AT, De Vivo I, Wong JYY, et al. Telomere length and early severe social deprivation: linking early adversity and cellular aging. Mol Psychiatry. 2012;17:719–27.PubMedCrossRef Drury SS, Theall K, Gleason MM, Smyke AT, De Vivo I, Wong JYY, et al. Telomere length and early severe social deprivation: linking early adversity and cellular aging. Mol Psychiatry. 2012;17:719–27.PubMedCrossRef
100.
go back to reference Brody GH, Gray JC, Yu T, Barton AW, Beach SR, Galván A, et al. Protective prevention effects on the association of poverty with brain development. JAMA Pediatr. 2017;171(1):46–52.PubMedCrossRef Brody GH, Gray JC, Yu T, Barton AW, Beach SR, Galván A, et al. Protective prevention effects on the association of poverty with brain development. JAMA Pediatr. 2017;171(1):46–52.PubMedCrossRef
101.
102.
go back to reference Shonkoff JP. Building a new biodevelopmental framework to guide the future of early childhood policy. Child Dev. 2010;81(1):357–67.PubMedCrossRef Shonkoff JP. Building a new biodevelopmental framework to guide the future of early childhood policy. Child Dev. 2010;81(1):357–67.PubMedCrossRef
106.
go back to reference World Health Organization. Preventing Child Maltreatment: A Guide to Taking Action and Generating Evidence. Geneva: WHO; 2006. World Health Organization. Preventing Child Maltreatment: A Guide to Taking Action and Generating Evidence. Geneva: WHO; 2006.
107.
go back to reference World Health Organization. mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-specialized Health Settings. Geneva: WHO; 2010. World Health Organization. mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-specialized Health Settings. Geneva: WHO; 2010.
110.
go back to reference World Health Organization. Advocacy for Mental Health: Mental Health Policy and Service Guidance Package. Geneva: WHO; 2003. World Health Organization. Advocacy for Mental Health: Mental Health Policy and Service Guidance Package. Geneva: WHO; 2003.
113.
go back to reference Bhutta ZA, Guerrant RL. Nelson 3rd CA. Neurodevelopment, nutrition, and inflammation: the evolving global child health landscape. Pediatrics. 2017;139 Suppl 1:S12–22.PubMedCrossRef Bhutta ZA, Guerrant RL. Nelson 3rd CA. Neurodevelopment, nutrition, and inflammation: the evolving global child health landscape. Pediatrics. 2017;139 Suppl 1:S12–22.PubMedCrossRef
Metadata
Title
Biological embedding of childhood adversity: from physiological mechanisms to clinical implications
Authors
Anne E. Berens
Sarah K. G. Jensen
Charles A. Nelson III
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0895-4

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