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Chronic stress profoundly affects mental health, significantly influencing mood, behavior, and overall quality of life. Research closely links chronic stress with mental health conditions such as depression, anxiety, and substance use disorders. Ongoing exposure to stress can lead to physiological and psychological changes, initiating a cycle of emotional distress and maladaptive coping mechanisms.
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Hypothalamic stress systems in mood disorders.

Florian Holsboer1, Marcus Ising2

  • 1HMNC Brain Health GmbH, Munich, Germany.

Handbook of Clinical Neurology
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Summary

Stress system dysfunction is common in depression. Targeting neuropeptide receptors may treat mood disorders, but requires companion tests to identify suitable patients for these novel therapies.

Keywords:
Corticotropin-releasing hormoneDepressionNeuropeptide SNeuropeptide YNeuropeptide receptorsOrexins/hypocretinsOxytocinVasopressin

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Psychiatry

Background:

  • Stress system dysfunction characterizes depression and mood disorders.
  • Corticosteroid receptor function influences neuroendocrine responses to stress, impacting resilience and risk for mental health conditions.
  • Neuropeptides like corticotropin-releasing hormone (CRH) and vasopressin (AVP) are key in stress adaptation.

Purpose of the Study:

  • To explore the role of neuropeptides in stress-related mental disorders.
  • To address the challenges in developing neuropeptide-based treatments for depression and anxiety.
  • To highlight the need for patient stratification in neuropeptide drug development.

Main Methods:

  • Review of neuroscience data on neuropeptide systems and stress response.
  • Analysis of clinical trial designs for neuropeptide receptor antagonists.
  • Conceptual framework for companion diagnostic development.

Main Results:

  • Neuropeptides (CRH, AVP, oxytocin, N S, N Y, orexin) are crucial for stress adaptation.
  • Neuropeptide receptors are specific targets for distinct patient populations.
  • Previous clinical trials failed due to a lack of patient stratification.

Conclusions:

  • Neuropeptide receptor-targeting drugs offer potential for treating stress-related disorders.
  • Effective clinical translation requires companion diagnostic tests to identify patient subgroups.
  • Future research must focus on developing these companion tests for personalized medicine approaches.