Neuroendocrine Modulation of Depression and Resilience
Summary
Depression and resilience are shaped by dynamic interactions between the nervous and endocrine systems, in which stress hormones, neuropeptides and growth factors modulate neural circuits underlying mood and coping. Central to this modulation is the hypothalamic–pituitary–adrenal (HPA) axis, whose dysregulation leads to altered cortisol release and impaired negative feedback in key limbic regions. Concurrently, adrenal-derived steroids such as dehydroepiandrosterone (DHEA) exert neuroprotective and antiglucocorticoid actions, buffering stress responses and promoting synaptic plasticity. Neuropeptides including oxytocin further influence social bonding and stress resilience by attenuating HPA axis activation and fostering adaptive coping strategies. Together, these neuroendocrine signals converge on prefrontal, hippocampal and amygdala circuits to determine vulnerability or resistance to mood disorders. Advances in understanding cellular and molecular mediators of these pathways have opened avenues for novel biomarkers and targeted interventions, ranging from pharmacological modulation of steroid receptors to psychosocial enrichment programmes. Given the global burden of depression, integrating neuroendocrine insights into prevention and treatment promises to enhance resilience across diverse populations.
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Neuroendocrine Modulation of Depression and Resilience publication trend
The graph below shows the total number of articles in neuroendocrine modulation of depression and resilience across all publications each year (not limited to Nature Index journals).
Technical terms
HPA axis: Hypothalamic–pituitary–adrenal axis, the principal neuroendocrine system controlling stress hormone release.
Cortisol: Primary glucocorticoid hormone that regulates energy metabolism and modulates mood under stress.
DHEA: Dehydroepiandrosterone, an adrenal steroid that counteracts glucocorticoid effects and supports neuroplasticity.
Oxytocin: Neuropeptide involved in social bonding and attenuation of the stress response.
Glucocorticoid receptor: Intracellular receptor mediating cellular responses to cortisol and shaping feedback regulation.
Resilience: The capacity to maintain or restore psychological well-being in the face of adversity.
References
- Enriched Environment Exposure Enhances Social Interactions and Oxytocin Responsiveness in Male Long-Evans Rats. Frontiers in Behavioral Neuroscience (2018).
- Contingency-based emotional resilience: effort-based reward training and flexible coping lead to adaptive responses to uncertainty in male rats. Frontiers in Behavioral Neuroscience (2014).
- Disrupted development from head to tail: Pervasive effects of postnatal restricted resources on neurobiological, behavioral, and morphometric outcomes. Frontiers in Behavioral Neuroscience (2022).
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