High plasma concentrations of cortisol and thromboxane B2 in patients with depression

Modulation of the hypothalamic-pituitary-adrenal axis in major depression is thought to depend on the hypothalamus and other areas of the central nervous system, or both. Hypothalamic over-activity may be responsible for the hypercortisolism observed in 50% of depressed subjects. To investigate the relation between psychosocial factors and cardiovascular disease, morning (8 AM) plasma concentrations of cortisol and thromboxane B2 (the stable metabolite of thromboxane A2, an eicosanoid closely linked to thrombotic disorders) were measured by radioimmunoassay in 32 patients with major depression (DSM III) triggered by psychosocial events and in 9 nondepressed volunteers. The depressed patients were studied in two groups, 16 with cortisol levels under 90 ng/mL and 16 with levels over 90 ng/mL. All the healthy non-depressed subjects had cortisol values over 100 ng/mL. The depressed patients with high cortisol had significantly higher plasma TxB2 concentrations than the other two groups. In addition, plasma cortisol and TxB2 concentrations correlated significantly over the whole group of depressed patients and in the high cortisol sub-group but not in the low-cortisol sub-group or in the nondepressed subjects. These findings appear to support the recently proposed role of the hypothalamic dysfunction associated with affective disorders in the pathogenesis of cardiovascular disease.