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

Christine Heim, Donald J Newport, Stacey Heit, Yolanda P. Graham, Molly Wilcox, Robert Bonsall, Andrew H. Miller, Charles Nemeroff

Research output: Contribution to journalArticle

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Abstract

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 petsistent 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 [Cl], 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% Cl, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% Cl, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001). Conclusion: 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.

Original languageEnglish
Pages (from-to)592-597
Number of pages6
JournalJournal of the American Medical Association
Volume284
Issue number5
StatePublished - Aug 2 2000
Externally publishedYes

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Sex Offenses
Depression
Corticotropin-Releasing Hormone
Psychological Stress
Adrenocorticotropic Hormone
Corticotropin-Releasing Hormone Receptors
Menstruation
Autonomic Nervous System
Disease Susceptibility
Anxiety Disorders
Mood Disorders
Bipolar Disorder
Psychotic Disorders
Substance-Related Disorders
Psychiatry
Hydrocortisone
Anxiety
Heart Rate
Outcome Assessment (Health Care)
Physical Abuse

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pituitary-adrenal and automatic responses to stress in women after sexual and physical abuse in childhood. / Heim, Christine; Newport, Donald J; Heit, Stacey; Graham, Yolanda P.; Wilcox, Molly; Bonsall, Robert; Miller, Andrew H.; Nemeroff, Charles.

In: Journal of the American Medical Association, Vol. 284, No. 5, 02.08.2000, p. 592-597.

Research output: Contribution to journalArticle

Heim, Christine ; Newport, Donald J ; Heit, Stacey ; Graham, Yolanda P. ; Wilcox, Molly ; Bonsall, Robert ; Miller, Andrew H. ; Nemeroff, Charles. / Pituitary-adrenal and automatic responses to stress in women after sexual and physical abuse in childhood. In: Journal of the American Medical Association. 2000 ; Vol. 284, No. 5. pp. 592-597.
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abstract = "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 petsistent 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 [Cl], 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{\%} Cl, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95{\%} Cl, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001). Conclusion: 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.",
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AU - Miller, Andrew H.

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N2 - 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 petsistent 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 [Cl], 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% Cl, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% Cl, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001). Conclusion: 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.

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