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Related Experiment Videos

Mineralocorticoid receptor function in major depression.

Elizabeth A Young1, Juan F Lopez, Virginia Murphy-Weinberg

  • 1Mental Health Research Institute and Department of Psychiatry, University of Michigan, 205 Zina Pitcher Pl, Ann Arbor, MI 48109-0720, USA. eayoung@umich.edu

Archives of General Psychiatry
|January 7, 2003
PubMed
Summary

Major depression is linked to increased mineralocorticoid receptor (MR) activity, contrary to expectations. This suggests an MR/GR imbalance may contribute to depression and serotonin system changes.

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Area of Science:

  • Neuroendocrinology
  • Psychiatry

Background:

  • The hypothalamic-pituitary-adrenal (HPA) axis is regulated by mineralocorticoid receptors (MR) and glucocorticoid receptors (GR).
  • MR activity is present throughout the circadian rhythm, while GR sensitivity may be reduced in major depression.
  • Glucocorticoids can down-regulate both MR and GR.

Purpose of the Study:

  • To investigate the functional activity of the MR system in individuals with major depression.
  • To test the hypothesis that major depression is associated with decreased MR activity.

Main Methods:

  • Spironolactone, an MR antagonist, was administered to patients with major depression and matched controls.
  • Corticotropin and cortisol secretion levels were assessed in response to spironolactone challenge.
  • Studies were conducted in the morning, during peak HPA axis activation, with medication-free participants.

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Main Results:

  • Spironolactone increased cortisol secretion in both depressed patients and controls.
  • Depressed patients exhibited higher cortisol secretion levels and a distinct pattern of increase post-spironolactone.
  • Spironolactone significantly affected corticotropin secretion in depressed patients, but not in controls.

Conclusions:

  • Major depression is characterized by high functional MR system activity, despite elevated baseline cortisol.
  • The findings suggest a potential imbalance in the MR/GR ratio in major depression.
  • This MR/GR imbalance may play a role in the etiology of depression and associated serotonin system alterations.