Current Developments in the Physiological Effects of Stress: Mechanisms and Health Consequences - Structured Narrative Review

Saeed Hameed Lafta

doi:10.59675/U414

Authors

Saeed Hameed Lafta Department of Physiology & Medical Physics, College of Medicine, Warith Al-Anbiyaa University, Karbala, Iraq Author

DOI:

https://doi.org/10.59675/U414

Keywords:

Stress; allostasis; HPA axis; autonomic nervous system; heart rate variability; cardiovascular disease; cognitive function.

Abstract

Background: Stress is an essential adaptive process that links neuroendocrine, autonomic, immunological, metabolic, and behavioural reactions to a perceived or real challenge. Generally, acute activation is protective, while chronic activation or insufficient recovery could lead to multisystem dysregulation and allostatic load over time.

Objectives: To integrate current literature regarding the physiological pathways involved in the relationship between acute and chronic psychological stress and health outcomes, with a particular focus on neuroendocrine, autonomic, immune, metabolic, neural, cardiovascular, mitochondrial and cellular-aging pathways.

Method: A structured narrative review was conducted on PubMed/MEDLINE, ScienceDirect/Elsevier LeapSpace and Google Scholar citation searching. We prioritized all human systematic reviews, meta-analyses, prospective cohorts, and experimental studies published from 2019 to September 2026, and included earlier seminal studies as needed to provide conceptual or mechanistic background. We did not quantitatively pool evidence; instead, we synthesized it thematically.

Results: The literature suggests a dynamic, context-dependent stress response leading to coordinated activation of the HPA axis and the autonomic nervous system. Persistent dysregulation is linked to disrupted cortisol function, decreased autonomic recovery, inflammation, metabolic dysfunction, cardiovascular risk, cognitive risk factors, and biological ageing. Few studies have directly tested human mitochondrial evidence, though cell-free mitochondrial DNA and related markers are promising biomarker candidates. Across domains, the best evidence supports multisystem associations, and causal inference and biomarker standardization remain key limitations.

Conclusions: stress results in a biological phenotype that is not homogeneous. Its effects are stressor-specific, time-dependent, recovery-dependent, adversity-history-dependent, and susceptibility- and measurement-dependent. Future studies should focus on longitudinal multimodal phenotyping, standardized biomarkers, and causal designs to elucidate the time window during which adaptive stress responses become biologically deleterious.

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