Altered pituitary-adrenal axis responses to provocative challenge tests inadult survivors of childhood abuse

Objective: Early adverse life events may predispose individuals to the deve lopment of mood and anxiety disorders in adulthood, perhaps by inducing per sistent changes in corticotropin-releasing factor (CRF) neuronal systems. T he present study sought to evaluate pituitary-adrenal responses to standard hypothalamic-pituitary-adrenal axis challenge tests in adult female surviv ors of childhood abuse with and without major depressive disorder. Method: Plasma ACTH and cortisol responses to the administration of 1 mug/k g ovine CRF and plasma cortisol responses to the administration of 250 mug ACTH(1-24) were measured in healthy women without early life stress (N=20), women with childhood abuse without major depressive disorder (N=20), women with childhood abuse and major depressive disorder (N= 15), and women with major depression but no early life stress (N=11). Results: Abused women without major depressive disorder exhibited greater t han usual ACTH responses to CRF administration, whereas abused women with m ajor depressive disorder a nd depressed women without early life stress dem onstrated blunted ACTH responses. In the ACTH(1-24) stimulation test, abuse d women without major depressive disorder exhibited lower baseline and stim ulated plasma cortisol concentrations. Abused women with comorbid depressio n more often suffered from posttraumatic stress disorder and reported more recent life stress than abused women without major depressive disorder. Conclusions: These findings suggest sensitization of the anterior pituitary and counterregulative adaptation of the adrenal cortex in abused women wit hout major depressive disorder. On subsequent stress exposure, women with a history of childhood abuse may hypersecrete CRF, resulting in down-regulat ion of adenohypophyseal CRF receptors and symptoms of depression and anxiet y.