Hormones, Stress and Depression

  • Marianne B. Müller
  • Florian Holsboer
Conference paper
Part of the Research and Perspectives in Endocrine Interactions book series (RPEI)


Every disturbance of the body, either real or imagined, evokes a stress response. Essential to this stress response is the activation of the hypothalamic-pituitary-adrenocortical (HPA) system, finally resulting in the release of glucocorticoid hormones from the adrenal cortex. Glucocorticoid hormones, in turn, feed back to this system by central activation of two types of corticosteroid receptors: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Whereas a brief period of controllable stress, experienced with general arousal and excitement, can be a challenge and might thus be beneficial, chronically elevated levels of circulating corticosteroid hormones are believed to enhance vulnerability to a variety of diseases, including human affective disorders.

The cumulative evidence makes a strong case implicating corticosteroid receptor dysfunction in the pathogenesis of affective disorders. Corticosteroid receptor dysfunction is followed by changes in the sensitivity of the system to the inhibitory effects of glucocorticoids on the synthesis of CRH and vasopressin in hypothalamic neurons. Changes in CRH and vasopressin levels, in turn, determine the responsiveness of the axis to subsequent stressors: increased production of these neuropeptides leads to increased HPA responses to stress and might be associated with an enhanced anxiety state. Although definitive controlled trials remain to be conducted, there is evidence indicating that cortisol-lowering or corticosteroid receptor antagonist treatments, as well as CRH type 1 receptor antagonists, may be of clinical benefit in individuals with major depression. Therefore, a more detailed knowledge of GR and CRH receptor signalling pathways will ultimately lead to the development of novel neuropharmacological intervention strategies.


Glucocorticoid Receptor Mineralocorticoid Receptor Dexamethasone Suppression Test Corticosteroid Receptor Corticosteroid Hormone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Marianne B. Müller
    • 1
  • Florian Holsboer
    • 1
  1. 1.Max Planck Institute of PsychiatryMunichGermany

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