Skip to main content

Advertisement

Log in

The enduring effects of abuse and related adverse experiences in childhood

A convergence of evidence from neurobiology and epidemiology

European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Background

Childhood maltreatment has been linked to a variety of changes in brain structure and function and stress–responsive neurobiological systems. Epidemiological studies have documented the impact of childhood maltreatment on health and emotional well–being.

Methods

After a brief review of the neurobiology of childhood trauma, we use the Adverse Childhood Experiences (ACE) Study as an epidemiological “case example” of the convergence between epidemiologic and neurobiological evidence of the effects of childhood trauma. The ACE Study included 17,337 adult HMO members and assessed 8 adverse childhood experiences (ACEs) including abuse, witnessing domestic violence, and serious household dysfunction. We used the number of ACEs (ACE score) as a measure of cumulative childhood stress and hypothesized a "doseresponse" relationship of the ACE score to 18 selected outcomes and to the total number of these outcomes (comorbidity).

Results

Based upon logistic regression analysis, the risk of every outcome in the affective, somatic, substance abuse, memory, sexual,and aggressionrelated domains increased in a graded fashion as the ACE score increased (P <0.001). The mean number of comorbid outcomes tripled across the range of the ACE score.

Conclusions

The graded relationship of the ACE score to 18 different outcomes in multiple domains theoretically parallels the cumulative exposure of the developing brain to the stress response with resulting impairment in multiple brain structures and functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abercrombie ED, Jacobs BL (1987) Single–unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. I. Acutely presented stressful and non–stressful stimuli. J Neurosci 7:2837–2847

    CAS  PubMed  Google Scholar 

  2. Anda RF, Chapman DP, Felitti VJ, Edwards VE, Williamson DF, Croft JP, Giles WH (2002a) Adverse Childhood Experiences and Risk of Paternity in Teen Pregnancy. Obstet Gynecol 100:37–45

    Article  Google Scholar 

  3. Anda RF, Croft JB, Felitti VJ, Nordenberg D, Giles WH, Williamson DF, Giovino GA (1999) Adverse childhood experiences and smoking during adolescence and adulthood. J Am Med Assoc 282:1652

    Article  CAS  Google Scholar 

  4. Anda RF, Felitti VJ, Chapman DP, Croft JB, Williamson DF, Santelli J, Dietz PM, Marks JS (2001) Abused boys, battered mothers, and male involvement in teen pregnancy. Pediatrics 107(2):e19

    Article  CAS  PubMed  Google Scholar 

  5. Anda RF, Whitfield CL, Felitti VJ, Chapman D, Edwards VJ, Dube SR, Williamson DF (2002b) Adverse childhood experiences, alcoholic parents and later risk of alcoholism and depression. Psychiatr Serv 53:1001–1009

    Article  Google Scholar 

  6. Anda RF, Williamson D, Jones D, Macera C, Eaker E, Glassman A, Marks J (1993) Depressed affect, hopelessness and the risk of ischemic heart disease in a cohort of US adults. Epidemiology 4:285–294

    Article  CAS  PubMed  Google Scholar 

  7. Anderson CM, Teicher MH, Polcari A, Renshaw PI (2002) Abnormal T2 relaxation time in the cerebellar vermis of adults sexually abused in childhood: potential role of the vermis in stress–enhanced risk for drug abuse. Psychoneuroendocrinology 27:231–244

    Article  PubMed  Google Scholar 

  8. Beers SR, De Bellis MD (2002) Neuropsychological function in children with maltreatment–related posttraumatic stress disorder. Am J Psychiatry 159(3):483–486

    Article  PubMed  Google Scholar 

  9. Bennett AJ, Lesch KP, Heils A, Long JC, Lorenz JG, Shoaf SE, Champoux M, Suomi SJ, Linnoila MV, Higley JD (2002) Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7:118–122

    Article  CAS  PubMed  Google Scholar 

  10. Bremner JD (2003a) Long–term effects of childhood abuse on brain and neurobiology. Child Adolesc Psychiatr Clin North Am 12:271–292

    Article  Google Scholar 

  11. Bremner JD (2003b) Does Stress Damage the Brain? Understanding trauma–based disorders from a neurological perspective. New York: Norton

    Google Scholar 

  12. Bremner JD, Krystal JH, Southwick SM, Charney DS (1996a) Noradrenergic mechanisms in stress and anxiety: I Preclinical studies. Synapse 23:28–38

    Article  CAS  Google Scholar 

  13. Bremner JD, Narayan M, Staib LH, Southwick SM, McGlashan T, Charney DS (1999) Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. Am J Psychiatry 156:1787–1795

    CAS  PubMed  Google Scholar 

  14. Bremner JD, Randall P, Scott TM, Capelli S, Delaney R, Mc– Carthy G, Charney DS (1995) Deficits in short–term memory in adult survivors of childhood abuse. Psychiatry Res 59:97–107

    Article  CAS  PubMed  Google Scholar 

  15. Bremner JD, Randall P, Vermetten E, Staib L, Bronen RA, Mazure C, Capelli S, McCarthy G, Innis RB, Charney DS (1997) Magnetic image resonance–based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse: a preliminary report. Biol Psychiatry 41:23–32

    Article  CAS  PubMed  Google Scholar 

  16. Bremner JD, Southwick M, Darnell MA, Charney DS (1996b) Chronic PTSD in Vietnam combat veterans: Course of illness and substance abuse. Am J Psychiatry 153:369–375

    CAS  Google Scholar 

  17. Bremner JD, Vermetten E (2001) Stress and development: behavioral and biological consequences. Dev Psychopathol 13:473–489

    Article  Google Scholar 

  18. Bremner JD, Vythilingam M, Anderson G, Vermetten E, Mc– Glashan T, Heninger G, Rasmusson A, Southwick SM, Charney DS (2003) Assessment of the hypothalamic–pituitary–adrenal (HPA) axis over a 24–hour diurnal period and in response to neuroendocrine challenges in women with and without early childhood sexual abuse and posttraumatic stress disorder (PTSD). Biol Psychiatry 54:710–718

    Article  CAS  PubMed  Google Scholar 

  19. Bremner JD, Vythilingam M, Vermetten E, Adil J, Khan S, Nazeer A, Afzal N, McGlashan T, Elzinga B, Anderson GM, Heninger G, Southwick SM, Charney DS (2003) Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse. Psychoneuroendocrinology 28:733–750

    Article  CAS  PubMed  Google Scholar 

  20. Bremner JD, Vythilingam M, Vermetten E, Southwick SM, Mc– Glashan T, Nazeer A, Khan S, Vaccarino LV, Soufer R, Garg PK, Ng CK, Staib LH, Duncan JS, Charney DS (2003) MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder. Am J Psychiatry 160:924–932

    Article  PubMed  Google Scholar 

  21. Brodsky BS, Malone KM, Ellis SP, Dulit RA, Mann JJ (1997) Characteristics of borderline personality disorder associated with suicidal behavior. Am J Psychiatry 154:1715–1719

    CAS  PubMed  Google Scholar 

  22. Brown D (2001) (Mis)representations of the long–term effects of childhood sexual abuse in the courts. J Child Sex Abuse 9:79–107

    Article  Google Scholar 

  23. Caldji C, Francis D, Sharma S, Plotsky PM, Meaney MJ (2000) The effects of early rearing environment on the development of GABA and central benzodiazepine receptor levels and noveltyinduced fearfulness in the rat. Neuropsychopharmacology 22:219–229

    Article  CAS  PubMed  Google Scholar 

  24. Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ (1998) Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci. USA 95:5335–5340

    Article  CAS  PubMed  Google Scholar 

  25. Carrion VG, Steiner H (2000) Trauma and dissociation in delinquent adolescents. J Am Acad Child Adolesc Psychiatry 39:353–359

    Article  CAS  PubMed  Google Scholar 

  26. Carrion VG, Weems CF, Eliez S, Patwardhan A, Brown W, Ray RD, Reiss AL (2001) Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder. Biol Psychiatry 50:943–951

    Article  CAS  PubMed  Google Scholar 

  27. Carrion VG, Weems CF, Ray RD, Glaser B, Hessl D, Reiss AL (2002) Diurnal salivary cortisol in pediatric posttraumatic stress disorder. J Biol Psychiatry 51:575–582

    Article  CAS  Google Scholar 

  28. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5–HTT gene. Science 301:386–389

    Article  CAS  PubMed  Google Scholar 

  29. CDC (2002) Annual smoking–attributable mortality, years of potential life lost, and economic costs – United States, 1995–1999. MMWR 51:300–303

    Google Scholar 

  30. Chapman DP, Anda RF, Felitti VJ, Dube SR, Edwards VJ, Whitfield CL (2004) Epidemiology of adverse childhood experiences and depressive disorders in a large health maintenance organization population. J Affect Disord 82:217–225

    Article  PubMed  Google Scholar 

  31. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress–induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Nat Acad Sci USA 98:12796–12801

    Article  CAS  PubMed  Google Scholar 

  32. De Bellis MD, Baum AS, Birmaher B, Keshavan MS, Eccard CH, Boring AM, Jenkins FJ, Ryan ND (1999) AE Bennett Research Award. Developmental traumatology. Part I: Biological stress systems. Biol Psychiatry 15(45):1259–1270

    Article  Google Scholar 

  33. De Bellis MD, Baum AS, Birmaher B, Ryan ND (1997) Urinary catecholamine excretion in childhood overanxious and posttraumatic stress disorders. Ann NY Acad Sci 821:451–455

    Article  CAS  PubMed  Google Scholar 

  34. DeBellis MD, Chrousos GP, Dorn LD, Burke L, Helmers K, Kling MA, Trickett PK, Putnam FW (1994) Hypothalamic–pituitaryadrenal axis dysregulation in sexually abused girls. J Clin Endocrinol Metab 78:249–255

    Article  CAS  Google Scholar 

  35. De Bellis MD, Keshavan MS, Clark DB, Casey BJ, Giedd JN, Boring AM, Frustaci K, Ryan ND (1999) AE Bennett Research Award. Developmental traumatology. Part II: Brain development. Biol Psychiatry 45:1271–1284

    Article  CAS  PubMed  Google Scholar 

  36. De Bellis MD, Keshavan MS, Shifflett H, Iyengar S, Beers SR, Hall J, Moritz G (2002) Brain structures in pediatric maltreatmentrelated posttraumatic stress disorder: a sociodemographically matched study. Biol Psychiatry 52:1066–1078

    Article  PubMed  Google Scholar 

  37. De Bellis M, Thomas L (2003) Biologic findings of post–traumatic stress disorder and child maltreatment. Curr Psychiatry Rep 5:108–117

    Article  PubMed  Google Scholar 

  38. DellaFemina D, Yeager CA, Lewis DO (1990) Child abuse: adolescent records vs. adult recall. Child Abuse Negl 14:227–231

    Article  CAS  Google Scholar 

  39. Deutch AY, Roth RH (1990) The determinants of stress–induced activation of the prefrontal cortical dopamine system. Prog Brain Res 85:367–402

    Article  CAS  PubMed  Google Scholar 

  40. Diamond DM, Fleshner M, Ingersoll N, Rose GM (1996) Psychological stress impairs spatial working memory: relevance to electrophysiological studies of hippocampal function. Behav Neurosci 110:661–672

    Article  CAS  PubMed  Google Scholar 

  41. Dietz PM, Spitz AM, Anda RF, Williamson DF, McMahon PM, Santelli JS, Nordenberg DF, Felitti VJ, Kendrick JS (1999) Unintended pregnancy among adult women exposed to abuse or household dysfunction during their childhood. J Am Med Assoc 282:1359–1364

    Article  CAS  Google Scholar 

  42. Dong M, Anda RF, Felitti VJ, Dube SR, Giles WH (2003a) The relationship of exposure to childhood sexual abuse to other forms of abuse, neglect and household dysfunction during childhood. Child Abuse Negl 27:625–639

    Article  Google Scholar 

  43. Dong M, Dube SR, Felitti VJ, Giles WH, Anda RF (2003b) Adverse childhood experiences and self–reported liver disease: new insights into a causal pathway. Arch Int Med 163:1949–1956

    Article  Google Scholar 

  44. Dube SR, Anda RF, Felitti VJ, Chapman D, Williamson DF, Giles WH (2001) Childhood abuse, household dysfunction and the risk of attempted suicide throughout the life span: findings from the Adverse Childhood Experiences Study. J Am Med Assoc 286:3089–3096

    Article  CAS  Google Scholar 

  45. Dube SR, Anda RF, Felitti VJ, Croft JB, Edwards VJ, Giles WH (2001) Growing up with Parental alcohol abuse: Exposure to childhood abuse, neglect and household dysfunction. Child Abuse Negl 25:1627–1640

    Article  CAS  PubMed  Google Scholar 

  46. Dube SR, Anda RF, Felitti VJ, Edwards VJ, Croft JB (2002a) Adverse childhood experiences and personal alcohol abuse as an adult. Addict Behav 27:713–725

    Article  Google Scholar 

  47. Dube SR, Anda RF, Felitti VJ, Edwards VJ, Williamson DF (2002b) Exposure to abuse, neglect and household dysfunction among adults who witnessed intimate partner violence as children. Violence Vict 17:3–17

    Article  Google Scholar 

  48. Dube SR, Felitti VJ, Chapman DP, Giles WH, Anda RF (2003a) Childhood abuse, neglect and household dysfunction and the risk of illicit drug use: the Adverse Childhood Experience Study. Pediatrics 111:564–572

    Article  Google Scholar 

  49. Dube SR, Felitti VJ, Dong M, Giles WH, Anda RF (2003b) The impact of adverse childhood experiences on health problems: evidence from four birth cohorts dating back to 1900. Prev Med 37:268–277

    Article  Google Scholar 

  50. Dube SR, Williamson DF, Thompson T, Felitti VJ, Anda RF (2004) Assessing the Reliability of Retrospective Reports of Adverse Childhood Experiences Among Adult HMO Members Attending a Primary Care Clinic. Child Abuse Negl 28(7):729–737

    Article  PubMed  Google Scholar 

  51. Driessen M, Herrmann J, Stahl K, Zwaan M, Meier S, Hill A, Osterheider M, Petersen D (2000) Magnetic resonance imaging volumes of the hippocampus and the Amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 57:1115–1122

    Article  CAS  PubMed  Google Scholar 

  52. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606

    CAS  PubMed  Google Scholar 

  53. Edwards VJ, Anda RF, Felitti VJ, Dube SR (2003a) Adverse childhood experiences and health–related quality of life as an adult. In: Kendall–Tackett K (ed) Victimization and Health, American Psychological Association, pp 81–94

  54. Edwards VJ, Anda RF, Nordenberg DF, Felitti VJ, Williamson DF, Wright JA (2001) Bias assessment or child abuse survey: factors affecting probability of response to a survey about childhood abuse. Child Abuse Negl 25:307–312

    Article  CAS  PubMed  Google Scholar 

  55. Edwards VJ, Fivush R, Anda RF, Felitti VJ, Nordenberg DF (2001) Autobiographical memory disturbances in childhood abuse survivors. In: Freyd JJ, DePrince AP (eds) Trauma and Cognitive Science: A meeting of minds, science, and human experience. Binghamton, NY: Haworth Press. Also published in Aggression, Maltreatment, and Trauma

  56. Edwards VJ, Holden GW, Anda RF, Felitti VJ (2003b) Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the Adverse Childhood Experiences (ACE) Study. Am J Psychiatry 160:1453–1460

    Article  Google Scholar 

  57. El–Sheikh M, Harger J, Whitson S (2001) Exposure to interparental conflict and children’s adjustment and physical health: the moderating role of vagal tone. Child Dev 72:1617–1636

    Article  CAS  PubMed  Google Scholar 

  58. Elzinga BM, Schmahl CG, Vermetten E, van Dyck R, Bremner JD (2003) Higher cortisol levels following exposure to traumatic reminders in abuse–related PTSD. Neuropsychopharmacology 28:1656–1665

    Article  CAS  PubMed  Google Scholar 

  59. Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, Koss MP, Marks JS (1998) Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences Study. Am J Prev Med 14:245–258

    Article  CAS  PubMed  Google Scholar 

  60. Finkelhor D, Hotaling G, Lewis IA, Smith C (1990) Sexual abuse in a national survey of adult men and women: prevalence, characteristics, and risk factors. Child Abuse Negl 14:19–28

    Article  CAS  PubMed  Google Scholar 

  61. Foote SL, Bloom E, Aston–Jones G (1983) Nucleus locus coeruleus: new evidence of anatomical and physiological specificity. Physiol Behav 63:844–914

    CAS  Google Scholar 

  62. Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ (1999) The role of corticotropin–releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry 46:1153–1166

    Article  CAS  PubMed  Google Scholar 

  63. Francis DD, Young LJ, Meaney MJ, Insel TR (2002) Naturally occurring differences in maternal care are associated with the expression of oxytocin and vasopression (V1a) receptors: gender differences. J Neuroendocrinol 14:349–353

    Article  CAS  PubMed  Google Scholar 

  64. Glaser D (2000) Child abuse and neglect and the brain: a review. J Child Psychol Psychiatry 41:97–116

    Article  CAS  PubMed  Google Scholar 

  65. Gorman JM, Mathew S, Coplan J (2002) Neurobiology of early life stress: nonhuman primate models. Clin Neuropsychiatry 7:96–103

    Article  Google Scholar 

  66. Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999a) Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2:260–265

    Article  CAS  Google Scholar 

  67. Gould E, McEwen BS, Tanapat P, Galea LA, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492–2498

    CAS  PubMed  Google Scholar 

  68. Gould E, Tanapat P (1999b) Stress and hippocampal neurogenesis. Biol Psychiatry 46:1472–1479

    Article  CAS  Google Scholar 

  69. Gutman D, Nemeroff CB (2002) Neurobiology of early life stress: rodent studies. Semin Clin Neuropsychiatry 7:89–95

    Article  PubMed  Google Scholar 

  70. Heffernan K, Cloitre M, Tardiff K, Marzuk PM, Portera L, Leon AC (2000) Childhood trauma as a correlate of lifetime opiate use in psychiatric patients. Addict Behav 25:797–803

    Article  CAS  PubMed  Google Scholar 

  71. Heim C, Nemeroff CB (2001) The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 49:1023–1039

    Article  CAS  PubMed  Google Scholar 

  72. Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB (2001) Altered pituitary–adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry 158:575–581

    Article  CAS  PubMed  Google Scholar 

  73. Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, Nemeroff CB (2000) Pituitary–adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. J Am Med Assoc 284:592–597

    Article  CAS  Google Scholar 

  74. Hillis SD, Anda RF, Dube SR, Felitti VJ, Marchbanks PA, Marks JS (2004) The association between adolescent pregnancy, longterm psychosocial outcomes, and fetal death. Pediatrics 113:320–327

    Article  PubMed  Google Scholar 

  75. Hillis SD, Anda RF, Felitti VJ, Marchbanks PA (2001) Adverse childhood experiences and sexual risk behaviors in women: a retrospective cohort study. Fam Plan Perspect 33:206–211

    Article  CAS  Google Scholar 

  76. Hillis SD, Anda RF, Felitti VJ, Nordenberg D, Marchbanks PA (2000) Adverse childhood experiences and sexually transmitted diseases in men and women: a retrospective study. Pediatrics 106:E11

    Article  CAS  PubMed  Google Scholar 

  77. Insel TR, Winslow J (1998) Serotonin and neuropeptides in affiliative behaviors. Biol Psychiatry 44:207–219

    Article  CAS  PubMed  Google Scholar 

  78. Ito Y, Teicher MH, Glod CA, Ackerman E (1998) Preliminary evidence for aberrant cortical development in abused children: a quantitative EEG study. J Neuropsychiatry Clin Neurosci 10:298–307

    CAS  PubMed  Google Scholar 

  79. Kaplan JR, Manuck SB, Clarkson TB, Luss M (1982) Social status, environment, and atherosclerosis in cynomolgus monkeys. Arteriosclerosis 2:359–368

    CAS  PubMed  Google Scholar 

  80. Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386:493–495

    Article  CAS  PubMed  Google Scholar 

  81. Kendall–Tackett KA, Williams LM, Finkelhor D (1993) Impact of sexual abuse on children: a review and synthesis of recent empirical studies. Psychol Bull 113:164–180

    Article  CAS  PubMed  Google Scholar 

  82. Kendler KS, Bulik CM, Silberg J, Hettema JM, Myers J, Prescott CA (2000) Childhood sexual abuse and adult psychiatric and substance abuse disorders in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry 57:953–959

    Article  CAS  PubMed  Google Scholar 

  83. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB (1995) Posttraumatic stress disorder in the national comorbidity survey. Arch Gen Psychiatry 52:1048–1060

    CAS  PubMed  Google Scholar 

  84. Kingree JB, Thompson MP, Kaslow NJ (1999) Risk factors for suicide attempts among low–income women with a history of alcohol problems. Addict Behav 24:583–587

    Article  CAS  PubMed  Google Scholar 

  85. Ladd CO, Owens MJ, Nemeroff CB (1996) Persistent changes in corticotropin–releasing factor neuronal systems induced by maternal separation. Endocrinology 137:1212–1218

    Article  CAS  PubMed  Google Scholar 

  86. Lemieux AM, Coe CL (1995) Abuse–related posttraumatic stress disorder: Evidence for chronic neuroendocrine activation in women. Psychosom Med 57:105–115

    CAS  PubMed  Google Scholar 

  87. Lilienfeld SO (2003) Comorbidity between and within childhood externalizing and internalizing disorders: reflections and directions. J Abn Child Psychol 32:285–291

    Article  Google Scholar 

  88. Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ (1997) Maternal care, hippocampal glucocorticoid receptors, and hypothalamic– pituitary–adrenal responses to stress. Science 277:1659–1662

    Article  CAS  PubMed  Google Scholar 

  89. Lo Re V, Bellini LM (2002) William of Occam and Occam’s razor (letter). Ann Int Med 136:634–635

    Google Scholar 

  90. Luine V, Villegas M, Mortinez C, McEwen BS (1994) Repeated stress causes reversible impairments of spatial memory performance. Brain Res 639:167–170

    Article  CAS  PubMed  Google Scholar 

  91. MacMillan HL, Fleming JE, Trocme N, Boyle MH, Wong M, Racine YA, Beardslee WR, Offord DR (1997) Prevalence of child physical and sexual abuse in the community: results from the Ontario Health Supplement. J Am Med Assoc 278:131–135

    Article  CAS  Google Scholar 

  92. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110

    CAS  PubMed  Google Scholar 

  93. McEwen BS, Angulo J, Cameron H, Chao HM, Daniels D, Gannon MN, Gould E, Mendelson S, Sakai R, Spencer R (1992) Paradoxical effects of adrenal steroids on the brain: Protection versus degeneration. Biol Psychiatry 31:177–199

    Article  CAS  PubMed  Google Scholar 

  94. McEwen BS, Stellar E (1993) Stress and the individual: mechanisms leading to disease. Arch Int Med 153:2093–2101

    Article  CAS  Google Scholar 

  95. Musselman DL, Evans DL, Nemeroff CB (1998) The relationship of depression to cardiovascular disease. Arch Gen Psychiatry 55:580–592

    Article  CAS  PubMed  Google Scholar 

  96. Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15:7539 –7547

    CAS  PubMed  Google Scholar 

  97. Osofsky JD (1999) The impact of violence on children. Future Child 99:33–49

    Article  Google Scholar 

  98. Perry BD (1994) Neurobiological Sequelae of Childhood Trauma: Post Traumatic Stress Disorders in Children. In: Murburg M (ed) Catecholamine Function in Post Traumatic Stress Disorder: Emerging Concepts. American Psychiatric Press, Washington, DC, pp 253–276

  99. Perry BD (2001) The neurodevelopmental impact of violence in childhood. In: Schetky D, Benedek EP (eds) Textbook of Child and Adolescent Forensic Psychiatry. American Psychiatric Press, Inc, Washington, DC pp 221–238

  100. Perry BD (2002) Childhood experience and the expression of genetic potential:What childhood neglect tells us about nature and nurture. Brain Mind 3:79–100

    Article  Google Scholar 

  101. Perry BD, Pollard R (1998) Homeostasis, stress, trauma, and adaptation. A neurodevelopmental view of childhood trauma. Child Adolesc Psychiatr Clin North Am 7:33–51, viii

    CAS  Google Scholar 

  102. Pinchus JH, Tucker GJ (1978) Behavioral Neurology, New York: Oxford

  103. Plotsky PM, Meaney MJ (1993) Early postnatal experience alters hypothalamic–corticotropin–releasing factor (CRF) mRNA, median eminence CRF content and stress–induced releasing in adult rats. Mol Brain Res 18:195–200

    Article  CAS  PubMed  Google Scholar 

  104. Putnam FW (1998) Developmental pathways in sexually abused girls. Presented at Psychological Trauma: Maturational Processes and Psychotherapeutic interventions. Harvard Medical School, Boston MA. March 20

    Google Scholar 

  105. Putnam FW (2003) Ten–year research update review; child sexual abuse. J Am Acad Child Adolesc Psychiatry 4:269–278

    Article  Google Scholar 

  106. Read J, Perry BD, Moskowith A, Connolloy J (2001) The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model. Psychiatry 64:319–345

    CAS  PubMed  Google Scholar 

  107. Repetti RL, Taylor SE, Seeman TE (2002) Risky families: family social environments and the mental and physical health of offspring. Psychol Bull 128:330–366

    Article  PubMed  Google Scholar 

  108. Rohsenow DJ, Corbett R, Devine D (1988) Molested as children: a hidden contribution to substance abuse? J Subst Abuse Treat 5:13–18

    Article  CAS  PubMed  Google Scholar 

  109. Rosenblum L, Coplan J, Friedman S, Bassoff T, Gormen JM, Andrews MW (1994) Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates. Biol Psychiatry 35:221–227

    Article  CAS  PubMed  Google Scholar 

  110. Rothman KJ, Greenland S (1998) Modern Epidemiology. Philadelphia. PA: Lippincott Raven Publications

  111. Rozanski A, Blumenthal JA, Kaplan J (1999) Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 99:2192–2217

    CAS  PubMed  Google Scholar 

  112. Sanchez MM, Ladd CO, Plotsky PM (2001) Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models. Dev Psychopathol 13:419–449

    Article  CAS  PubMed  Google Scholar 

  113. Sapolsky RM (1996) Why stress is bad for your brain. Science 273:749–750

    Article  CAS  PubMed  Google Scholar 

  114. Sapolsky RM, Uno H, Rebert CS, Finch CE (1990) Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci 10:2897–2902

    CAS  PubMed  Google Scholar 

  115. Scaer RC (2001) The neurophysiology of dissociation and chronic disease. Appl Psychophysiol Biofeedback 26:73–91

    Article  CAS  PubMed  Google Scholar 

  116. Schmahl CG, Vermetten E, Elzinga BM, Bremner JD (2003) Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder. Psychiatry Res 122:193–198

    Article  PubMed  Google Scholar 

  117. Schoenborn CA (1991) Exposure to alcoholism in the family: United States, 1988. Adv Data 205:1–13

    PubMed  Google Scholar 

  118. Shin LH, McNally RJ, Kosslyn SM, Thompson WL, Rauch SL, Alpert NM, Metzger LJ, Lasko NB, Orr SP, Pitman RK (1999) Regional cerebral blood flow during script–driven imagery in childhood sexual abuse–related PTSD: a PET investigation. Am J Psychiatry 156:575–584

    CAS  PubMed  Google Scholar 

  119. Smith MA, Kim SY, van Oers HJ, Levine S (1997) Maternal deprivation and stress induce immediate early genes in the infant rat brain. Endocrinology 138:4622–4628

    Article  CAS  PubMed  Google Scholar 

  120. Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B (1997) Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med 27:1–9

    Article  Google Scholar 

  121. Straus M, Gelles J (1990) Physical Violence in American Families: Risk Factors and Adaptations to Violence in 8, 145 Families. New Brunswick, NJ: Transaction Press

  122. Teicher MH (2000) Wounds that time wouldn’t heal: the neurobiology of childhood abuse. Cerebrum 2:50–67

    Google Scholar 

  123. Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP (2002) Developmental neurobiology of childhood stress and trauma. Psychiatr Clin North Am 25:397–426, vii–viii

    Article  PubMed  Google Scholar 

  124. Teicher MH, Ito Y, Glod CA, Andersen SL, Dumont N, Ackerman E (1997) Preliminary evidence for abnormal cortical development in physically and sexually abused children using EEG coherence and MRI. Ann N Y Acad Sci 821:160–175

    Article  CAS  PubMed  Google Scholar 

  125. Teicher MH, Ito Y, Glod CA, Schiffer F, Ackerman E (1994) Possible effects of early abuse on human brain development, as assessed by EEG coherence. Am J Neuropsychopharmacol 33:52

    Google Scholar 

  126. Valenstein ES (1998) Blaming the Brain: The Truth About Drugs and Mental Health. Basic Books, NY

    Google Scholar 

  127. van der Kolk BA, Perry JC, Herman JL (1991) Childhood origins of self–destructive behavior. Am J Psychiatry 148:1665–1671

    CAS  PubMed  Google Scholar 

  128. van Reekum R, Streiner DL, Conn DK (2001) Applying Bradford Hill’s criteria for causation to neuropsychiatry: challenges and opportunities. J Neuropsychiatry Clin Neurosci 12:318–325

    Google Scholar 

  129. Volkow ND, Fowler JS, Wang GJ (2003) The addicted human brain: insights from imaging studies. J Clin Invest 111:1444–1451

    Article  CAS  PubMed  Google Scholar 

  130. Vythilingam M, Heim C, Newport CD, Miller AH, Anderson E, Bronen R, Brummer M, Staib L, Vermetten E, Charney DS, Nemeroff CB, Bremner JD (2002) Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry 159:2072–2080

    Article  PubMed  Google Scholar 

  131. Whitfield CL, Anda RF, Dube SR, Felitti VJ (2003a) Violent childhood experiences and the risk of intimate partner violence in adults: assessment in a large health maintenance organization. J Interpersonal Violence 18:166–185

    Article  Google Scholar 

  132. Whitfield CL (2003b) The Truth about Depression: Choices for Healing. Deerfield Beach, FL: Health Communications

  133. Williams LM (1995) Recovered memories of abuse in women with documented child sexual victimization histories. J Trauma Stress 8:649–673

    Article  CAS  PubMed  Google Scholar 

  134. Williamson DF, Thompson TJ, Anda RF, Dietz WH, Felitti VJ (2002) Body weight, obesity, and self–reported abuse in childhood. Int J Obesity 26:1075–1082

    Article  CAS  Google Scholar 

  135. Wyatt GE (1985) The sexual abuse of Afro–American and white–American women in childhood. Child Abuse Negl 9:507–519

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The ACE study was supported under cooperative agreement #TS–44–10/11 from the CDC through the Association of Teachers of Preventive Medicine and a grant from the Garfield Memorial Fund.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anda, R.F., Felitti, V.J., Bremner, J.D. et al. The enduring effects of abuse and related adverse experiences in childhood. Eur Arch Psychiatry Clin Neurosci 256, 174–186 (2006). https://doi.org/10.1007/s00406-005-0624-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-005-0624-4

Key words

Navigation