The Dexamethasone/Corticotropin-Releasing Factor Test in Men with Major Depression: Role of Childhood Trauma

Background: The dexamethasone/corticotropin-releasing factor (CRF) test is considered to be the most sensitive measure of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and has been demonstrated to be altered in patients with major depression (MDD). Although childhood trauma is a demonstrated risk factor for MDD and patients with a history of childhood abuse and MDD demonstrate HPA axis hyperactivity, the dexamethasone/CRF test remains unstudied in this population. We determined the impact of childhood trauma on dexamethasone/CRF test results in patients with MDD. Methods: Forty-nine healthy men, ages 18-60 years, without mania or psychosis, active substance abuse, or eating disorder and medication-free were recruited into four study groups, including: 1) normal subjects with no childhood abuse history or psychiatric disorder (n = 14); 2) men with childhood abuse histories without current MDD (n = 14); 3) men with childhood abuse histories with current MDD (n = 15); and 4) men with current MDD and no childhood abuse history (n = 6). Plasma adrenocorticotropin (ACTH) and cortisol concentrations were measured in response to dexamethasone/CRF administration. Results: Men with childhood trauma histories exhibited increases in ACTH and cortisol responses to dexamethasone/CRF compared with non-abused men. In particular, abused men with current MDD showed increased responsiveness compared with control subjects and depressed men without childhood abuse experience. Increased response was associated with the severity, duration, and earlier onset of the abuse. The effects were not explained by concurrent posttraumatic stress disorder. Conclusions: Childhood trauma increases HPA axis activity as measured with the dexamethasone/CRF test in adult men with MDD, potentially reflecting environmental risk for developing depression.