The Long-Term Impact of Early Adversity on Late-Life Psychiatric Disorders

  • Anda GershonEmail author
  • Keith Sudheimer
  • Rabindra Tirouvanziam
  • Leanne M. Williams
  • Ruth O’Hara
Geriatric Disorders (H Lavretsky, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Geriatric Disorders


Early adversity is a strong and enduring predictor of psychiatric disorders including mood disorders, anxiety disorders, substance abuse or dependence, and posttraumatic stress disorder. However, the mechanisms of this effect are not well understood. The purpose of this review is to summarize and integrate the current research knowledge pertaining to the long-term effects of early adversity on psychiatric disorders, particularly in late life. We explore definitional considerations including key dimensions of the experience such as type, severity, and timing of adversity relative to development. We then review the potential biological and environmental mediators and moderators of the relationships between early adversity and psychiatric disorders. We conclude with clinical implications, methodological challenges and suggestions for future research.


Stress Psychological Childhood maltreatment Childhood adversity Late life Psychiatric disorders Risk factors HPA function Immune dysregulation Adult stressors Gender Genetic markers Geriatric Psychiatry 



Preparation of this report was supported by the Department of Veterans Affairs Advanced Fellowship Program in War Related and Unexplained Illness awarded to A. Gershon.

Conflict of Interest

Anda Gershon declares that she has no conflict of interest.

Keith Sudheimer declares that he has no conflict of interest.

Rabindra Tirouvanziam declares that he has no conflict of interest.

Leanne M. Williams declares that she has no conflict of interest.

Ruth O’Hara declares that she has no conflict of interest.


Papers of particular interest, published recently, have been highlighted as:• Of importance

  1. 1.
    Bifulco A, Brown GW, Adler Z. Early sexual abuse and clinical depression in adult life. Br J Psychiatry. 1991;159:115–22.PubMedCrossRefGoogle Scholar
  2. 2.
    Green JG, McLaughlin KA, Berglund PA, et al. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010;67(2):113–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Kendler KS, Bulik CM, Silberg J, et al. Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry. 2000;57(10):953–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Kendler KS, Gardner CO, Prescott CA. Toward a comprehensive developmental model for major depression in women. Am J Psychiatry. 2002;159(7):1133–45.PubMedCrossRefGoogle Scholar
  5. 5.
    Kendler KS, Gardner CO, Prescott CA. Toward a comprehensive developmental model for major depression in men. Am J Psychiatry. 2006;163(1):115–24.PubMedCrossRefGoogle Scholar
  6. 6.
    Kessler RC, Davis CG, Kendler KS. Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey. Psychol Med. 1997;27(5):1101–19.PubMedCrossRefGoogle Scholar
  7. 7.
    Kessler RC, Magee WJ. Childhood family violence and adult recurrent depression. J Health Soc Behav. 1994;35(1):13–27.PubMedCrossRefGoogle Scholar
  8. 8.
    MacMillan HL, Fleming JE, Streiner DL, et al. Childhood abuse and lifetime psychopathology in a community sample. Am J Psychiatry. 2001;158(11):1878–83.PubMedCrossRefGoogle Scholar
  9. 9.
    Molnar BE, Buka SL, Kessler RC. Child sexual abuse and subsequent psychopathology: results from the National Comorbidity Survey. Am J Public Health. 2001;91(5):753–60.PubMedCrossRefGoogle Scholar
  10. 10.
    Nelson EC, Heath AC, Madden PAF, et al. Association between self-reported childhood sexual abuse and adverse psychosocial outcomes: results from a twin study. Arch Gen Psychiatry. 2002;59(2):139–45.PubMedCrossRefGoogle Scholar
  11. 11.
    Widom CS. Posttraumatic stress disorder in abused and neglected children grown up. Am J Psychiatry. 1999;156(8):1223–9.PubMedGoogle Scholar
  12. 12.
    Afifi 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(6):814–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Clark C, Caldwell T, Power C, et al. Does the influence of childhood adversity on psychopathology persist across the lifecourse? A 45-year prospective epidemiologic study. Ann Epidemiol. 2010;20(5):385–94.PubMedCrossRefGoogle Scholar
  14. 14.
    Comijs HC, Beekman AT, Smit F, et al. Childhood adversity, recent life events and depression in late life. J Affect Disord. 2007;103(1–3):243–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Kivela SL, Luukinen H, Koski K, et al. Early loss of mother or father predicts depression in old age. Int J Geriatr Psychiatry. 1998;13(8):527–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Wilson RS, Krueger KR, Arnold SE, et al. Childhood adversity and psychosocial adjustment in old age. Am J Geriatr Psychiatry. 2006;14(4):307–15.PubMedCrossRefGoogle Scholar
  17. 17.
    • Chu DA, Williams LM, Harrisa AWF, et al. Early life trauma predicts self-reported levels of depressive and anxiety symptoms in nonclinical community adults: relative contributions of early life stressor types and adult trauma exposure. J Psychiatr Res. 2013;47(1):23–32. One of the few and largest studies to investigate how exposure to early life trauma contributes to depression and anxiety disorders in later life, using a fine-grained assessment of early life stress than is typical of epidemiological investigations. Findings underline the relative importance of early exposure tointerpersonal violationrelative to other types of early stressors for future psychiatric risk.PubMedCrossRefGoogle Scholar
  18. 18.
    McMahon SD, Grant KE, Compas BE, et al. Stress and psychopathology in children and adolescents: is there evidence of specificity? J Child Psychol Psychiatry. 2003;44(1):107–33.PubMedCrossRefGoogle Scholar
  19. 19.
    McLaughlin KA, Green JG, Gruber MJ, et al. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. Arch Gen Psychiatry. 2010;67:124–32.PubMedCrossRefGoogle Scholar
  20. 20.
    Kessler RC, McLaughlin KA, Green JG, et al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry. 2010;197(5):378–85.PubMedCrossRefGoogle Scholar
  21. 21.
    Finkelhor D, Ormrod RK, Turner HA. Re-victimization patterns in a national longitudinal sample of children and youth. Child Abuse Negl. 2007;31(5):479–502.PubMedCrossRefGoogle Scholar
  22. 22.
    Wise LA, Zierler S, Krieger N, et al. Adult onset of major depressive disorder in relation to early life violent victimisation: a case-control study. Lancet. 2001;358(9285):881–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Felitti VJ, Anda RF, Nordenberg D, 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.PubMedCrossRefGoogle Scholar
  24. 24.
    Evans GW, Schamberg MA. Childhood poverty, chronic stress, and adult working memory. Proc Natl Acad Sci U S A. 2009;106(16):6545–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Draper B, Pfaff JJ, Pirkis J, et al. Depression and Early Prevention of Suicide in General Practice Study Group. Long-term effects of childhood abuse on the quality of life and health of older people: results from the Depression and Early Prevention of Suicide in General Practice Project. J Am Geriatr Soc. 2008;56(2):262–71.PubMedCrossRefGoogle Scholar
  26. 26.
    Kaplow JB, Dodge KA, Amaya-Jackson L, et al. Pathways to PTSD, part II: sexually abused children. Am J Psychiatry. 2005;162(7):1305–10.PubMedCrossRefGoogle Scholar
  27. 27.
    Rudolph KD, Flynn M. Childhood adversity and youth depression: influence of gender and pubertal status. Dev Psychopathol. 2007;19(2):497–521.PubMedCrossRefGoogle Scholar
  28. 28.
    Schoedl AF, Costa MC, Mari JJ, et al. The clinical correlates of reported childhood sexual abuse: an association between age at trauma onset and severity of depression and PTSD in adults. J Child Sex Abus. 2010;19(2):156–70.PubMedCrossRefGoogle Scholar
  29. 29.
    Kaplow JB, Widom CS. Age of onset of child maltreatment predicts long-term mental health outcomes. J Abnorm Psychol. 2007;116(1):176–87.PubMedCrossRefGoogle Scholar
  30. 30.
    Yehuda R, Golier JA, Halligan SL, et al. Learning and memory in Holocaust survivors with posttraumatic stress disorder. Biol Psychiatry. 2004;55(3):291–5.PubMedCrossRefGoogle Scholar
  31. 31.
    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(6):959–97.PubMedCrossRefGoogle Scholar
  32. 32.
    Hazel NA, Hammen C, Brennan PA, et al. Early childhood adversity and adolescent depression: the mediating role of continued stress. Psychol Med. 2008;38(4):581–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Pearlin LI. The sociological study of stress. J Health Soc Behav. 1998;30(3):241–56.CrossRefGoogle Scholar
  34. 34.
    Gunnar M, Quevedo K. The neurobiology of stress and development. Ann Rev Psychol. 2007;58:145–73.CrossRefGoogle Scholar
  35. 35.
    Heim C, Newport DJ, Bonsall R, et al. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry. 2001;158(4):575–81.PubMedCrossRefGoogle Scholar
  36. 36.
    Kaufman J, Plotsky PM, Nemeroff CB, et al. Effects of early adverse experiences on brain structure and function: clinical implications. BPS. 2000;48(8):778–90.Google Scholar
  37. 37.
    Abercrombie HC, Jahn AL, Davidson RJ, et al. Cortisol’s effects on hippocampal activation in depressed patients are related to alterations in memory formation. J Psychiatr Res. 2011;45(1):15–23.PubMedCrossRefGoogle Scholar
  38. 38.
    de Quervain DJ, Henke K, Aerni A, et al. Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe. Eur J Neurosci. 2003;17(6):1296–302.PubMedCrossRefGoogle Scholar
  39. 39.
    Karst H, Nair S, Velzing E, et al. Glucocorticoids alter calcium conductances and calcium channel subunit expression in basolateral amygdala neurons. Eur J Neurosci. 2002;16(6):1083–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Mitra R, Sapolsky RM. Gene therapy in rodent amygdala against fear disorders. Expert Opin Biol Ther. 2010;10(9):1289–303.PubMedCrossRefGoogle Scholar
  41. 41.
    Spangler G, Grossmann KE. Biobehavioral organization in securely and insecurely attached infants. Child Dev. 1993;64(5):1439–50.PubMedCrossRefGoogle Scholar
  42. 42.
    King JA, Mandansky D, King S, et al. Early sexual abuse and low cortisol. Psychiatry Clin Neurosci. 2001;55(1):71–4.PubMedCrossRefGoogle Scholar
  43. 43.
    De Bellis MD, Chrousos GP, Dorn LD, et al. Hypothalamic–pituitary–adrenal axis dysregulation in sexually abused girls. J Clin Endocrinol Metab. 1994;78(2):249–55.PubMedCrossRefGoogle Scholar
  44. 44.
    Gerritsen L, Geerlings MI, Beekman AT, et al. Early and late life events and salivary cortisol in older persons. Psychol Med. 2010;40(9):1569–78.PubMedCrossRefGoogle Scholar
  45. 45.
    Stein MB, Yehuda R, Koverola C, et al. Enhanced dexamethasone suppression of plasma cortisol in adult women traumatized by childhood sexual abuse. Biol Psychiatry. 1997;42(8):680–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Heim C, Newport DJ, Heit S, et al. Pituitary–adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA. 2000;284(5):592–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Yehuda R, Golier JA, Kaufman S. Circadian rhythm of salivary cortisol in Holocaust survivors with and without PTSD. Am J Psychiatry. 2005;162(5):998–1000.PubMedCrossRefGoogle Scholar
  48. 48.
    Sudheimer K, Flournoy J, Gershon A, et al. HPA axis and late life depression. In: Lavretsky H, Sajatovic M, Reynolds CF, editors. Late-life mood disorders. New York: Oxford University Press; 2013.Google Scholar
  49. 49.
    Graham JE, Christian LM, Kiecolt-Glaser JK. Stress, age, and immune function: toward a lifespan approach. J Behav Med. 2006;29(4):389–400.PubMedCrossRefGoogle Scholar
  50. 50.
    Langley-Evans SC, McMullen S. Developmental origins of adult disease. Med Princ Pract. 2010;19(2):87–98.PubMedCrossRefGoogle Scholar
  51. 51.
    Merlot E, Couret D, Otten W. Prenatal stress, fetal imprinting and immunity. Brain Behav Immun. 2008;22(1):42–51.PubMedCrossRefGoogle Scholar
  52. 52.
    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.PubMedCrossRefGoogle Scholar
  53. 53.
    Bellinger DL, Lubahn C, Lorton D. Maternal and early life stress effects on immune function: relevance to immunotoxicology. J Immunotoxicol. 2008;5(4):419–44.PubMedCrossRefGoogle Scholar
  54. 54.
    Bauer ME, Wieck A, Lopes RP, et al. Interplay between neuroimmunoendocrine systems during post-traumatic stress disorder: a minireview. Neuroimmunomodulation. 2010;17(3):192–5.PubMedCrossRefGoogle Scholar
  55. 55.
    Danese A, Pariante CM, Caspi A, et al. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci U S A. 2007;104(4):1319–24.PubMedCrossRefGoogle Scholar
  56. 56.
    Kiecolt-Glaser JK, Gouin JP, Weng NP, et al. Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation. Psychosom Med. 2011;73(1):16–22.PubMedCrossRefGoogle Scholar
  57. 57.
    Gouin JP, Glaser R, Malarkey WB, et al. Childhood abuse and inflammatory responses to daily stressors. Ann Behav Med. 2012;44(2):287–92.PubMedCrossRefGoogle Scholar
  58. 58.
    Macphee AG, Divol L, Kemp AJ, et al. Limitation on prepulse level for cone-guided fast-ignition inertial confinement fusion. Phys Rev Lett. 2010;104(5):055002.PubMedCrossRefGoogle Scholar
  59. 59.
    McLeod JD. Childhood parental loss and adult depression. J Health Soc Behav. 1991;35:205–20.CrossRefGoogle Scholar
  60. 60.
    Gorey KM, Leslie DR. The prevalence of child sexual abuse: integrative review adjustment for potential response and measurement biases. Child Abuse Negl. 1997;21(4):391–8.PubMedCrossRefGoogle Scholar
  61. 61.
    MacMillan HL, Fleming JE, Trocme N, et al. Prevalence of child physical and sexual abuse in the community. Results from the Ontario Health Supplement. JAMA. 1997;278(2):131–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Gershon A, Minor K, Hayward C. Gender, victimization, and psychiatric outcomes. Psychol Med. 2008;38(10):1377–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Caspi A, Hariri AR, Holmes A, et al. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry. 2010;167(5):509–27.PubMedCrossRefGoogle Scholar
  64. 64.
    Williams LM, Gatt JM, Schofield PR, et al. ‘Negativity bias’ in risk for depression and anxiety: brain–body fear circuitry correlates, 5-HTT-LPR and early life stress. NeuroImage. 2009;47(3):804–14.PubMedCrossRefGoogle Scholar
  65. 65.
    Aas M, Djurovic S, Athanasiu L, et al. Serotonin transporter gene polymorphism, childhood trauma, and cognition in patients with psychotic disorders. Schizophr Bull. 2010;38(1):15–22.CrossRefGoogle Scholar
  66. 66.
    Caspi 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(5631):386–9.PubMedCrossRefGoogle Scholar
  67. 67.
    O’Hara R, Schroder CM, Mahadevan R, et al. Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol. Mol Psychiatry. 2007;12(6):544–55.PubMedCrossRefGoogle Scholar
  68. 68.
    Gillespie NA, Whitfield JB, Williams B, et al. The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychol Med. 2005;35(1):101–11.PubMedCrossRefGoogle Scholar
  69. 69.
    Bet PM, Penninx BW, Bochdanovits Z, et al. Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: new evidence for a gene–environment interaction. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(5):660–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Binder 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(11):1291–305.PubMedCrossRefGoogle Scholar
  71. 71.
    Lesch KP. When the serotonin transporter gene meets adversity: the contribution of animal models to understanding epigenetic mechanisms in affective disorders and resilience. Curr Top Behav Neurosci. 2011;7:251–80.PubMedCrossRefGoogle Scholar
  72. 72.
    Sterley TL, Howells FM, Russell VA. Effects of early life trauma are dependent on genetic predisposition: a rat study. Behav Brain Funct. 2011;7:11.PubMedCrossRefGoogle Scholar
  73. 73.
    Hariri AR. Genetic polymorphisms: a cornerstone of translational biobehavioral research. Sci Transl Med. 2010;2(18):18ps6.PubMedCrossRefGoogle Scholar
  74. 74.
    Macrì S, Spinelli S, Adriani W, et al. Early adversity and alcohol availability persistently modify serotonin and hypothalamic–pituitary–adrenal–axis metabolism and related behavior: what experimental research on rodents and primates can tell us. Neurosci Biobehav Rev. 2007;31(2):172–80.PubMedCrossRefGoogle Scholar
  75. 75.
    George ED, Bordner KA, Elwafi HM, et al. Maternal separation with early weaning: a novel mouse model of early life neglect. BMC Neurosci. 2010;11:123.PubMedCrossRefGoogle Scholar
  76. 76.
    Baram TZ, Davis EP, Obenaus A, et al. Fragmentation and unpredictability of early-life experience in mental disorders. Am J Psychiatry. 2012;169(9):907–15.PubMedCrossRefGoogle Scholar
  77. 77.
    Wilkin MM, Waters P, McCormick CM, et al. Intermittent physical stress during early- and mid-adolescence differentially alters rats’ anxiety- and depression-like behaviors in adulthood. Behav Neurosci. 2012;126(2):344–60.PubMedCrossRefGoogle Scholar
  78. 78.
    Harro J. Animal models of depression vulnerability. Curr Top Behav Neurosci. 2012. doi: 10.1007/7854_2012_221.
  79. 79.
    Berton O, Hahn CG, Thase ME. Are we getting closer to valid translational models for major depression? Science. 2012;338(6103):75–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Dzirasa K, Covington 3rd HE. Increasing the validity of experimental models for depression. Ann N Y Acad Sci. 2012;1265:36–45.PubMedCrossRefGoogle Scholar
  81. 81.
    Pajer K, Andrus BM, Gardner W, et al. Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression. Transl Psychiatry. 2012;2:e101.PubMedCrossRefGoogle Scholar
  82. 82.
    Pryce CR, Rüedi-Bettschen D, Dettling AC, et al. Long-term effects of early-life environmental manipulations in rodents and primates: potential animal models in depression research. Neurosci Biobehav Rev. 2005;29(4–5):649–74.PubMedCrossRefGoogle Scholar
  83. 83.
    • Reed AE, Carstensen LL. The theory behind the age-related positivity effect. Front Psychol. 2012;3:339. doi: 10.3389/fpsyg.2012.00339. A striking finding from the field of aging is thepositivity effect”, which refers to older adultstendency to attend to and remember more positive than negative information, relative to younger adults. This article provides an overview of the theoretical basis of the positivity effect, discussing the implications of this phenomenon for consideration of emotional processing in older adults.PubMedCrossRefGoogle Scholar
  84. 84.
    Brewin CR, Andrews B, Gotlib IH. Psychopathology and early experience: a reappraisal of retrospective reports. Psychol Bull. 1993;113(1):82–98.PubMedCrossRefGoogle Scholar
  85. 85.
    Brown GW, Harris TO. Social origins of depression: a study of psychiatric disorder in women (1st American ed.). New York: Free Press; 1998.Google Scholar
  86. 86.
    Thompson WK, Hallmayer J, O’Hara R. Design considerations for characterizing psychiatric trajectories across the lifespan: application to effects of APOE-epsilon4 on cerebral cortical thickness in Alzheimer’s disease. Am J Psychiatry. 2011;168(9):894–903.PubMedCrossRefGoogle Scholar
  87. 87.
    MacLeod J, Nelson G. Programs for the promotion of family wellness and the prevention of child maltreatment: a meta-analytic review. Child Abuse Negl. 2000;24:1127–49.PubMedCrossRefGoogle Scholar
  88. 88.
    Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology. 2012;37(1):137–62.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Anda Gershon
    • 1
    • 2
    Email author
  • Keith Sudheimer
    • 1
  • Rabindra Tirouvanziam
    • 3
  • Leanne M. Williams
    • 1
  • Ruth O’Hara
    • 1
    • 2
  1. 1.Department of Psychiatry and Behavioral SciencesStanford University School of MedicineStanfordUSA
  2. 2.Sierra Pacific Mental Illness Research Education and Clinical Center (MIRECC)Palo Alto, Veterans Health Care SystemPalo AltoUSA
  3. 3.Department of PediatricsEmory University School of MedicineAtlantaUSA

Personalised recommendations