Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood

JAMA. 2000 Aug 2;284(5):592-7. doi: 10.1001/jama.284.5.592.


Context: Evidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-releasing factor (CRF) systems may mediate this association.

Objective: To determine whether early-life stress results in a persistent sensitization of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby contributing to vulnerability to psychopathological conditions.

Design and setting: Prospective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emory University Hospital, Atlanta, Ga.

Participants: Forty-nine healthy women aged 18 to 45 years with regular menses, with no history of mania or psychosis, with no active substance abuse or eating disorder within 6 months, and who were free of hormonal and psychotropic medications were recruited into 4 study groups (n = 12 with no history of childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of current major depression who were sexually or physically abused as children; n = 14 without current major depression who were sexually or physically abused as children; and n = 10 with diagnosis of current major depression and no history of childhood abuse).

Main outcome measures: Adrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to a standardized psychosocial laboratory stressor compared among the 4 study groups.

Results: Women with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. This effect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major depression diagnosis exhibited a more than 6-fold greater ACTH response to stress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60. 4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001).

Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions. Furthermore, these results imply a role for CRF receptor antagonists in the prevention and treatment of psychopathological conditions related to early-life stress. JAMA. 2000;284:592-597

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Adult
  • Anxiety / etiology
  • Anxiety / physiopathology
  • Anxiety / psychology
  • Autonomic Nervous System / physiology
  • Child
  • Child Abuse / psychology*
  • Cohort Studies
  • Depressive Disorder / etiology
  • Depressive Disorder / physiopathology
  • Depressive Disorder / psychology
  • Female
  • Heart Rate
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / physiology*
  • Life Change Events*
  • Middle Aged
  • Pituitary-Adrenal System / physiology*
  • Prospective Studies
  • Sex Offenses / psychology*
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / physiopathology


  • Adrenocorticotropic Hormone
  • Hydrocortisone