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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.

Depressive symptoms not only impair quality of life in cancer patients but constitute an independent risk factor for increased mortality. In order to accurately and efficiently identify depression in cancer patients, the authors developed a biostatistical strategy to identify items of the 21-item, observer-rated Hamilton Rating Scale for Depression (Ham-D) that would optimize the diagnosis of depression among cancer patients. Exhibiting a relatively high sensitivity and specificity, our most optimal diagnostic tool contained six Ham-D items (late insomnia, agitation, psychic anxiety, diurnal mood variation, depressed mood, and genital symptoms). This study may serve as a prototype to generate valid instruments accurate for the diagnosis of major depression in other populations of cancer patients.

Background: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-alpha therapy., Methods: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFN-alpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity., Results: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-alpha therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients., Conclusions: The results suggest that reduced TRP availability plays a role in IFN-alpha-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-alpha, attenuates the behavioral consequences of IFN-alpha-mediated TRP depletion.

This article reviews the rapidly accumulating literature on the relationship between mood disorders and diabetes mellitus. Recent studies have demonstrated that depression and its associated symptoms constitute a major risk factor in the development of type 2 diabetes and may accelerate the onset of diabetes complications. Since the mid-1980s, multiple longitudinal and cross-sectional studies have scrutinized the association of diabetes with depressive symptoms and major depression. Utilizing the search terms depressive disorders, psychiatry, diabetes, and pathophysiology in MEDLINE searches (1966-2003), this article reviews studies investigating pathophysiological alterations related to glucose intolerance and diabetes in depressed patients. The few randomized, controlled studies of treatment of depression in patients with diabetes are also described. Short-term treatment of depression in patients with diabetes improves their dysphoria and other signs and symptoms of depression. Future research will confirm whether response to psychotherapy and/or psychopharmacologic treatment improves glucose control, encourages compliance with diabetes treatment, and perhaps even increases longevity.