Depression, adrenal steroids, and the immune system.

During the past decade, over 30 studies have examined the immune system in depression. While a number of investigators have reported depression-related alterations in peripheral blood immune cell number and function, many researchers have been unable to replicate these findings. The relationship between depression and the immune system has turned out to be much more complex than was initially anticipated. Factors which have complicated the interpretation of the research include the heterogeneity of depressed patients, the variability of immune assays, and the clinical relevance of these assays. In this review we conclude that alterations in the immune system do not appear to be a specific or reproducible biological correlate of depression but may occur in association with other variables which characterize depressed patients including age, sex and severity of depression. Conceptual frameworks for future research on the immune system and depression are discussed and include: (i) depression as a cofactor in the development, course and outcome of diseases involving the immune system; (ii) depression as a neuroimmunological disease; and (iii) depression as a model for studying neuroendocrine-immune interactions in humans. In terms of this third line of research, patients with depression consistently have been shown to display abnormalities in the secretion of adrenal steroids, and new data is presented which indicates that adrenal steroids may play a much more complex role in the modulation of the immune response than has been previously appreciated.