Psychoneuroendocrinology of Stress Disorders

Psychoneuroendocrinology examines how psychological stressors engage neural circuits and hormonal systems to influence health and behaviour. Central to this field is the hypothalamic–pituitary–adrenal (HPA) axis, which orchestrates the release of corticotrophin-releasing hormone from the hypothalamus, adrenocorticotropic hormone from the pituitary and cortisol from the adrenal cortex. Acute activation of this axis facilitates adaptation to threat via metabolic mobilisation, heightened arousal and immune modulation. Chronic or dysregulated activation, however, can lead to maladaptive changes in brain structures—particularly the hippocampus, amygdala and prefrontal cortex—resulting in cognitive impairments, altered fear processing and emotional dysregulation. Individual vulnerability to stress disorders is shaped by genetic and epigenetic variation in HPA-axis regulatory genes, early-life adversity and sex-specific factors. Neuroendocrine biomarkers such as salivary cortisol and catecholamine levels have been investigated as predictors of symptom onset and treatment response, while interventions targeting glucocorticoid signalling show promise as adjuncts to psychotherapy. Beyond the HPA axis, interactions with the hypothalamic–pituitary–thyroid and hypothalamic–pituitary–gonadal axes, as well as neuromodulators like oxytocin and growth hormone, are increasingly recognised as contributors to stress resilience and disorder. Integrating endocrine, neural and behavioural data offers pathways towards personalised prevention strategies and treatment enhancers, with global implications for mental health care.

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Psychoneuroendocrinology of Stress Disorders publication trend

The graph below shows the total number of articles in psychoneuroendocrinology of stress disorders across all publications each year (not limited to Nature Index journals).

Technical terms

HPA axis: The network of hypothalamus, pituitary gland and adrenal cortex that controls stress hormone release.

Cortisol: A glucocorticoid hormone released by the adrenal glands in response to stress, affecting metabolism and immune function.

Extinction learning: A process by which conditioned fear responses decrease through repeated safe exposure to a threat cue.

Epigenetic modification: Stable changes in gene expression caused by chemical marks on DNA or histones, without altering the genetic code.

Glucocorticoid receptor (GR): A nuclear receptor that binds cortisol and mediates its effects on target cells, including feedback regulation of the HPA axis.

References

1. Exogenous glucocorticoids to improve extinction learning for post-traumatic stress disorder patients with hypothalamic–pituitary–adrenal-axis dysregulation: a study protocol description. European Journal of Psychotraumatology (2024).
2. Salivary cortisol in post-traumatic stress disorder: a systematic review and meta-analysis. BMC Psychiatry (2018).
3. Catecholamines in Post-traumatic Stress Disorder: A Systematic Review and Meta-Analysis. Frontiers in Molecular Neuroscience (2018).
4. Hypothalamus and Post-Traumatic Stress Disorder: A Review. Brain Sciences (2023).
5. The Pathways between Cortisol-Related Regulation Genes and PTSD Psychotherapy. Healthcare (2020).