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.