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Abstract
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.
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.
Prospective controlled study conducted from May 1997 to July 1999 at the General Clinical
Research Center of Emory University Hospital, Atlanta, Ga.
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).
Adrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to
a standardized psychosocial laboratory stressor compared among the 4 study groups.
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).
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