Cause or consequence? Understanding the role of cortisol in the increased inflammation observed in depression

Glucocorticoids such as cortisol are a class of steroid hormones that play an important role in co-ordinating the body's response to stress. Elevated cortisol levels and increased inflammation have frequently been reported in patients with depression. The currently accepted ‘glucocorticoid resistance’ model posits this increased inflammation as a consequence of reduced sensitivity to cortisol’s putative anti-inflammatory action. However, opposing evidence has accumulated that supports a more recent model, which instead proposes that cortisol possesses immune potentiating properties and may thus directly cause the increased inflammation seen in depression. Despite all of this, a clear explanation of the neuroendocrine mechanism that contributes to the development of depression is still lacking and thus requires further investigation in improved future studies.