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

Context Evidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-re leasing factor (CRF) systems may mediate this association. Objective To determine whether early-life stress results in a persistent se nsitization of the hypothalamic-pituitary-adrenal axis to mild stress in ad ulthood, thereby contributing to vulnerability to psychopathological condit ions, Design and Setting Prospective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emery University Hospi tal, Atlanta, Ga. Participants Forty-nine healthy women aged 18 to 45 years with regular mens es, with no history of mania or psychosis, with no active substance abuse o r eating disorder within 6 months, and who were free of hormonal and psycho tropic medications were recruited into 4 study groups (n = 12 with no histo ry of childhood abuse or psychiatric disorder [controls]; n =13 with diagno sis of current major depression who were sexually or physically abused as c hildren; n = 14 without current major depression who were sexually or physi cally abused as children; and n = 10 with diagnosis of current major depres sion and no history of childhood abuse). Main Outcome Measures Adrenocorticotropic hormone (ACTH) and cortisol level s and heart rate responses to a standardized psychosocial laboratory stress or compared among the 4 study groups. Results Women with a history of childhood abuse exhibited increased pituita ry-adrenal and autonomic responses to stress compared with controls. This e ffect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major de pression diagnosis exhibited a more than 6-fold greater ACTH response to st ress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/ml]; 95% co nfidence 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 hy persecretion, is a persistent consequence of childhood abuse that may contr ibute to the diathesis for adulthood psychopathological conditions. Further more, these results imply a role for CRF receptor antagonists in the preven tion and treatment of psychopathological conditions related to early-life s tress.