HPA Axis & Cortisol Modulation — References

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Parent Topic: HPA Axis & Cortisol Modulation | References Hub: 01 - Foundations References MOC

Primary Literature & Landmark Studies

Citation: McEwen, B. S. (1998). Protective and damaging effects of stress mediators. New England Journal of Medicine, 338(3), 171–179.
Identifiers: DOI: 10.1056/NEJM199801153380307 (DOI · SciDB · Scholar) | PMID: 9428819 (PubMed · Europe PMC) | Companion Neurobiology Review: McEwen (2007), Physiological Reviews, 87(3), 873–904, DOI: 10.1152/physrev.00041.2006 (DOI · SciDB · Scholar) (PMID: 17615391 (PubMed · Europe PMC))
Study Design: Landmark neuroendocrine and clinical synthesis defining allostasis and allostatic load across four failure archetypes (repeated hits, lack of adaptation, prolonged response / failure to shut off evening cortisol, and inadequate/blunted CAR response).
Key Quantitative Outcomes:
- Demonstrated that sustained glucocorticoid elevation and loss of diurnal trough inhibit adult neurogenesis in the dentate gyrus, induce reversible apical dendritic atrophy in hippocampal CA3 and medial prefrontal cortex (mPFC) neurons, and drive dendritic arborization and synaptic spinogenesis in the basolateral amygdala, locking the organism into chronic hypervigilance and metabolic insulin resistance.

Citation: Adam, E. K., Quinn, M. E., Tavernier, R., McQuillan, M. T., Dahlke, K. A., & Gilbert, K. E. (2017). Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis. Psychoneuroendocrinology, 83, 25–41.
Identifiers: DOI: 10.1016/j.psyneuen.2017.05.018 (DOI · SciDB · Scholar) | PMID: 28578301 (PubMed · Europe PMC)
Study Design: Systematic review and meta-analysis of 80 studies ( $N = 36, 939$ individuals) examining associations between diurnal salivary cortisol slopes (awakening/morning to evening decline) and 12 mental and physical health domains.
Key Quantitative Outcomes:
- A flatter diurnal cortisol slope (failure to suppress evening cortisol) was significantly associated with poorer overall health across all studies ( $r = 0.147, p < 0.001$ ), with particularly strong effect sizes for immune and inflammatory dysregulation ( $r = 0.289$ ), obesity/adiposity ( $r = 0.244$ ), cancer outcomes ( $r = 0.233$ ), fatigue ( $r = 0.219$ ), and depression ( $r = 0.125$ ).

Citation: Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root in reducing stress and anxiety in adults. Indian Journal of Psychological Medicine, 34(3), 255–262.
Identifiers: DOI: 10.4103/0253-7176.106022 (DOI · SciDB · Scholar) | PMID: 23439798 (PubMed · Europe PMC)
Study Design: 60-day prospective, randomized, double-blind, placebo-controlled trial in adults with chronic stress ( $N = 64$ ; 300 mg twice daily [600 mg/day] KSM-66 Withania somnifera root extract vs. placebo).
Key Quantitative Outcomes:
- Ashwagandha supplementation reduced serum cortisol levels by 27.9% from baseline (vs. 7.9% in placebo; $p = 0.0006$ ), reduced Perceived Stress Scale (PSS) scores by 44.0% ( $p < 0.0001$ ), and reduced GHQ-28 anxiety and insomnia subscale scores by 69.7% ( $p < 0.0001$ ) with no serious adverse events.

Citation: Starks, M. A., Starks, S. L., Kingsley, M., Purpura, M., & Jäger, R. (2008). The effects of phosphatidylserine on endocrine response to moderate intensity exercise. Journal of the International Society of Sports Nutrition, 5, 11.
Identifiers: DOI: 10.1186/1550-2783-5-11 (DOI · SciDB · Scholar) | PMID: 18662395 (PubMed · Europe PMC) | Companion Dose-Response Trial: Monteleone et al. (1992), Eur J Clin Pharmacol, 42(4), 385–388, DOI: 10.1007/BF00280123 (DOI · SciDB · Scholar) (PMID: 1325348 (PubMed · Europe PMC))
Study Design: 10-day randomized, double-blind, placebo-controlled crossover trial in healthy males ( $N = 10$ ; 600 mg/day soy-derived phosphatidylserine vs. placebo prior to graded cycle ergometer exercise).
Key Quantitative Outcomes:
- Phosphatidylserine (600 mg/day) lowered peak plasma cortisol concentrations by 39% ( $p = 0.004$ ) and cortisol area under the curve (AUC) by 35% ( $p = 0.008$ ) while increasing the testosterone-to-cortisol AUC ratio by 184% ( $p = 0.02$ ).