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The Trier Social Stress Test Protocol for Inducing Psychological Stress
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Hypothalamic-pituitary-adrenal axis and stress.

Carolin Leistner1, Andreas Menke2

  • 1Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, Wuerzburg, Germany.

Handbook of Clinical Neurology
|October 3, 2020
PubMed
Summary

Women exhibit greater stress-related mental health issues due to sex differences in the hypothalamic-pituitary-adrenal (HPA) axis response. This review examines HPA axis function in males and females across species.

Keywords:
FKBP5GenderGlucocorticoid receptorHPA axisHypothalamic–pituitary–adrenal axisSex

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Area of Science:

  • Neuroendocrinology
  • Psychiatry
  • Comparative Biology

Background:

  • Stress significantly contributes to mental disorders, with higher prevalence in women, including major depression and PTSD.
  • The hypothalamic-pituitary-adrenal (HPA) axis is a key neuroendocrine system regulating stress responses, crucial for maintaining health.
  • HPA axis dysregulation is implicated in various mental and physical disorders, highlighting its critical role.

Purpose of the Study:

  • To review and synthesize existing literature on sex differences in HPA axis function in response to stress.
  • To explore how these sex differences in HPA axis regulation may contribute to the higher incidence of stress-related mental disorders in women.
  • To compare findings from preclinical rodent models with human studies regarding HPA axis sex dimorphisms.

Main Methods:

  • Review of preclinical rodent studies investigating sex-based differences in HPA axis activation and stress hormone output.
  • Analysis of human studies examining HPA axis responses to various stressors, considering factors like contraceptive use and menstrual cycle phase.
  • Synthesis of literature comparing HPA axis function between males and females in response to acute and chronic stress.

Main Results:

  • Preclinical models consistently demonstrate that the female HPA axis exhibits a more rapid activation and greater stress hormone release compared to males.
  • Human studies present inconsistent findings, potentially due to variations in stressor types, hormonal contraceptive use, and menstrual cycle stage in female participants.
  • Evidence suggests significant sex differences in HPA axis regulation, though direct translation from animal models to humans requires careful consideration of confounding factors.

Conclusions:

  • Sex differences in HPA axis regulation are evident and may partially explain the higher prevalence of stress-related disorders in women.
  • Further research in humans is needed to reconcile inconsistent findings and clarify the precise mechanisms underlying HPA axis sex dimorphisms.
  • Understanding these sex differences is crucial for developing targeted prevention and treatment strategies for stress-related mental health conditions.