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Related Experiment Video

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An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
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The HPA Axis as Target for Depression.

Andreas Menke1,2

  • 1Department of Psychosomatic Medicine and Psychotherapy, Medical Park Chiemseeblick, Rasthausstr, 25, 83233 Bernau am Chiemsee, Germany.

Current Neuropharmacology
|August 15, 2023
PubMed
Summary

Major depressive disorder (MDD) involves the hypothalamus-pituitary-adrenal (HPA) axis. Targeting HPA axis components shows promise, with diagnostic tests enabling personalized MDD treatments.

Keywords:
CRH1FKBP5HPA axisSSR149415V1B receptor antagonistantidepressantsbiomarkersdepressionglucocorticoid receptor.precision medicinestressvasopressin

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Endocrinology

Background:

  • Major depressive disorder (MDD) is a prevalent, stress-related mental health condition affecting 20% of the population worldwide.
  • Abnormalities in the hypothalamus-pituitary-adrenal (HPA) axis are strongly implicated in the development of MDD.
  • Existing research highlights the HPA axis's central role in MDD pathophysiology.

Purpose of the Study:

  • To review current therapeutic strategies targeting the HPA axis for MDD treatment.
  • To explore the potential of novel drug targets within the HPA axis.
  • To emphasize the importance of diagnostic tools for precision medicine in MDD.

Main Methods:

  • Review of preclinical and clinical studies on HPA axis modulators for MDD.
  • Investigation of drug candidates including CRH1 receptor antagonists, vasopressin V1B receptor antagonists, glucocorticoid receptor antagonists, and FKBP5 antagonists.
  • Analysis of diagnostic tests like the dexamethasone-corticotrophin-releasing hormone (dex-CRH) test and molecular dexamethasone suppression (mDST) test.

Main Results:

  • Vasopressin V1B receptor antagonists and glucocorticoid receptor antagonists have shown the most promising clinical results to date.
  • FKBP5 antagonists demonstrate preclinical support and may mediate ketamine's effects.
  • HPA axis dysregulation is present only in a subset of MDD patients.

Conclusions:

  • Targeting specific HPA axis components offers potential for MDD treatment, particularly in patient subsets with HPA axis alterations.
  • Diagnostic tests are crucial for identifying patients who will benefit from HPA axis-targeted therapies.
  • Implementing companion diagnostics will facilitate a precision medicine approach for tailored MDD treatment.