Issue 24-1, 2025

Review

https://doi.org/10.38025/2078-1962-2025-24-1-67-74

Advanced Capabilities for In Vitro Stress Diagnostics: a Review

View article (Download PDF file)



Download XML file

* ORCIDYana G. Pekhova, ORCIDAnna A. Kuzyukova, ORCIDLarisa A. Marchenkova

National Medical Research Center for Rehabilitation and Balneology, Moscow, Russia


ABSTRACT

INTRODUCTION. The effects of stress negatively affect both physical and mental health. Recently, there has been a sharp increase in interest in studying evidence-based methods for diagnosing stress and effective interventions for its correction.

AIM. Comprehensive assessment of modern possibilities of stress objectification using laboratory diagnostics of its markers based on data from literary sources.

MATERIALS AND METHODS. To select publications, we studied the PubMed, Web of Science (Web of Science Core Collection and Medline), Cochrane Library databases, included data from meta-analyses and review articles, full-text articles investigating the relationship between laboratory biomarkers and stress. The search depth of publications was 10 years, from 2014 to 2024, and a number of earlier, fundamental works on the neurophysiology of stress were also included in the review.

RESULTS AND DISCUSSION Cortisol is the most reliable and frequently used laboratory marker of both acute and chronic stress, while the study of other potential biomarkers continues to grow. Psychometric questionnaires and functional diagnostic methods reflecting the degree of sympathetic activation are widely used in stress diagnostics. The integrated use of various diagnostic tools, including laboratory biomarkers of stress, will provide a multimodal approach, will contribute to a more complete picture of the stress response and will increase the degree of verification of stress conditions.

CONCLUSION.  The effectiveness of training according to the target parameter of electromyogram amplitude for automated locomotion (walking), in the presence of paresis of the central genesis, can be questioned and requires further research.


KEYWORDS: stress, chronic stress, biomarkers, cortisol, salivary cortisol, urinary cortisol, hair cortisol, salivary alpha-amylase, dehydroepiandrosterone, sympathetic-adrenal system, hypothalamic-pituitary-adrenal axis

FOR CITATION:

Pehova Ya.G., Kuzyukova A.A., Marchenkova L.A. Advanced Capabilities for In Vitro Stress Diagnostics: a Review.Bulletin of Rehabilitation Medicine. 2025; 24(1):67–74. https://doi.org/10.38025/2078-1962-2025-24-1-67-74 (In Russ.).

FOR CORRESPONDENCE: Yana G. Pekhova, Е-mail: pehovayg@nmicrk.ru


References:

  1. Engert V., Linz R., Grant J.A. Embodied stress: The physiological resonance of psychosocial stress. Psychoneuroendocrinology. 2019; 105: 138–146. https://doi.org/10.1016/j.psyneuen.2018.12.221
  2. Chrousos G.P. Stress and disorders of the stress system. Nat Rev Endocrinol. 2009; 5(7): 374–381. https://doi.org/10.1038/nrendo.2009.106
  3. Behrends J., Bischofberger J., Deutzmann R. et al. Physiologie. Stuttgart: Thieme. 2017; 831 p. https://dx.doi.org/10.1055/b-004-132217
  4. Giacomello G., Scholten A., Parr M.K. Current methods for stress marker detection in saliva. J Pharm Biomed Anal. 2020; 191: 113604. https://doi.org/10.1016/j.jpba.2020.113604
  5. McEwen B.S., Bowles N.P., Gray J.D. et al. Mechanisms of stress in the brain. Nature Neuroscience. 2015; 18(10): 1353–1363. https://doi.org/10.1038/nn.4086
  6. Shields G.S, Sazma M.A., Yonelinas A.P. The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol. Neurosci Biobehav Rev. 2016; 68: 651–668. https://doi.org/10.1016/j.neubiorev.2016.06.038
  7. Sapolsky R.M. Glucocorticoids, the evolution of the stress-response, and the primate predicament. Neurobiol Stress. 2021; 14: 100320. https://doi.org/10.1016/j.ynstr.2021.100320
  8. Eddy P., Wertheim E.H., Hale M.W. et al. A Systematic Review and Revised Meta-analysis of the Effort-Reward Imbalance Model of Workplace Stress and Hypothalamic-Pituitary-Adrenal Axis Measures of Stress. Psychosom Med. 2023; 85(5): 450–460. https://doi.org/10.1097/PSY.0000000000001155
  9. Marty M.A., Sega S.L. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th Ed. American Psychiatric Publishing. 2013; 947 p.
  10. Chow Y., Masiak J., Mikotajewska E. et al. Limbic brain structures and burnout-A systematic review. Adv Med Sci. 2018; 63(1): 192–198. https://doi.org/10.1016/j.advms.2017.11.004
  11. Engel S., Laufer S., Klusmann H. et al. Cortisol response to traumatic stress to predict PTSD symptom development — a systematic review and meta-analysis of experimental studies. Eur J Psychotraumatol. 2023; 14(2): 2225153. https://doi.org/10.1080/20008066.2023.2225153
  12. Rincon-Cortes M., Herman J.P., Lupien S. et al. Stress: Influence of sex, reproductive status and gender. Neurobiol Stress. 2019; 9(10): 100155. https://dx.doi.org/10.1016/j.ynstr.2019.100155
  13. Woo E., Sansing L.H., Arnsten A.F.T. et al. Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes. Chronic Stress (Thousand Oaks). 2021; 5: 24705470211029254. https://doi.org/10.1177/24705470211029254
  14. Agorastos A., Chrousos G.P. The neuroendocrinology of stress: The stress-related continuum of chronic disease development. Mol Psychiatry. 2022; 27(1): 502–513. https://doi.org/10.1038/s41380-021-01224-9
  15. Ganesan A., Kumar G., Gauthaman J. et al. Exploring the Relationship between Psychoneuroimmunology and Oral Diseases: A Comprehensive Review and Analysis. J Lifestyle Med. 2024; 14(1): 13–19. https://doi.org/10.15280/jlm.2024.14.1.13
  16. Balasamy S., Atchudan R., Arya S. et al. Cortisol: Biosensing and detection strategies. Clin Chim Acta. 2024; 562: 119888. https://doi.org/10.1016/j.cca.2024.119888
  17. Iob E., Steptoe A. Cardiovascular Disease and Hair Cortisol: a Novel Biomarker of Chronic Stress. Current Cardiology Reports. 2019; 21(10): 116. https://doi.org/10.1007/s11886-019-1208-7
  18. Noushad Sh., Ahmed S., Ansari B. et al. Physiological biomarkers of chronic stress: A systematic review. Int J Health Sci (Qassim). 2021; 15(5): 46–59.
  19. Kokka I., Chrousos G.P., Darviri C. et al. Measuring Adolescent Chronic Stress: A Review of Established Biomarkers and Psychometric Instruments. Horm Res Paediatr. 2023; 96(1): 74–82. https://doi.org/10.1159/000522387
  20. Iqbal T., Elahi A., Wijns W. et al. Cortisol detection methods for stress monitoring in connected health. Health Sciences Review. 2023; 6(3): 100079. https://doi.org/10.1016/j.hsr.2023.100079
  21. Nater U.M., Skoluda N., Strahler J. Biomarkers of stress in behavioural medicine. Curr Opin Psychiatry. 2013; 26(5): 440–445. https://dx.doi.org/10.1097/YCO.0b013e328363b4ed
  22. Tian R., Hou G., Song L. et al. Chronic grouped social restriction triggers long-lasting immune system adaptations. Oncotarget. 2017; 8(20): 33652–33657. https://doi.org/10.18632/oncotarget.16856
  23. Kiecolt-Glaser J.K., Preacher K.J., MacCallum R.C. et al. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA. 2003; 100(15): 9090–9095. https://doi.org/10.1073/pnas.1531903100
  24. Mert M., Tanakol R., Karpuzoglu H. et al. Spectral effect: each population must have its own normal midnight salivary cortisol reference values determined. Arch. Med. Sci. 2013; 9: 872–876. https://doi.org/10.5114/aoms.2013.38681
  25. Adam E.K., Quinn M.E., Tavernier R. et al. Diurnal cortisol slopes and mental and physical health out-comes: A systematic review and meta-analysis. Psychoneuroendocrinology. 2017; 83: 25–41. https://dx.doi.org/10.1016/j.psyneuen.2017.05.018
  26. Rogerson O., Wilding S., Prudenzi A. et al. Effectiveness of stress management interventions to change cortisol levels: a systematic review and meta-analysis. Psychoneuroendocrinology. 2024; 159: 106415. https://doi.org/10.1016/j.psyneuen.2023.106415
  27. Ostinelli G., Scovronec AIcetaS., Ouellette A.S. et al. Deciphering the Association Between Hypothalamus-Pituitary-Adrenal Axis Activity and Obesity: A Meta-Analysis. Obesity (Silver Spring). 2021; 29(5): 846–858. https://doi.org/10.1002/oby.23125
  28. De Vente W., Olff M., Van Amsterdam J. et al. Physiological differences between burnout patients and healthy controls: Blood pressure, heart rate, and cortisol responses. Occup Environ Med. 2003; 60(Suppl. 1): i54–61. https://doi.org/10.1136/oem.60.suppl_1.i54
  29. Lovallo W.R. Stress and Health: Biological and Psychological Interactions. Thousand Oaks. CA: SAGE. 3rd Ed. 2016. 352 p.
  30. Benz A., Meier M., Mankin M. et al. The duration of the cortisol awakening pulse exceeds sixty minutes in a meaningful pattern. Psychoneuroendocrinology. 2019; 105: 187–194. https://doi.org/10.1016/j.psyneuen.2018.12.225
  31. John K.A., Cogswell M.E., Campbell N.R. et al. Accuracy and Usefulness of Select Methods for Assessing Complete Collection of 24-Hour Urine: A Systematic Review. J Clin Hypertens (Greenwich). 2016; 18(5): 456–467. https://doi.org/10.1111/jch.12763
  32. Steckl A.J., Ray P. Stress biomarkers in biological fluids and their point-of-Use detection. ACS Sens. 2018; 3(10): 2025–2044. https://doi.org/10.1021/acssensors.8b00726
  33. O’Connor D.B., Gartland N., O’Connor R.C. Stress, cortisol and suicide risk Int. Rev. Neurobiol. 2020; 152: 101–130. https://doi.org/10.1016/bs.irn.2019.11.006
  34. Ruttle P.L., Javaras K.N., Klein M.H. et al. Concurrent and longitudinal associations between diurnal cortisol and body mass index across adolescence. J. Adolesc. Health. 2013; 52(6): 731–737. https://doi.org/10.1016/j.jadohealth.2012.11.013
  35. Stalder T., Steudte-Schmiedgen S., Alexander N. et al. Stress-related and basic determinants of hair cortisol in humans: A metaanalysis. Psychoneuroendocrinology. 2017; 77: 261–274. https://dx.doi.org/10.1016/j.psyneuen.2016.12.017
  36. Li Y., Jia W., Yan N. et al. Associations between chronic stress and hair cortisol in children: A systematic review and meta-analysis. J Affect Disord. 2023; 329: 438–447. https://doi.org/10.1016/j.jad.2023.02.123
  37. Pageau L.M., Ng T.J., Ling J. et al. Associations between hair cortisol and blood pressure: a systematic review and meta-analysis. J Hypertens. 2023; 41(6): 875–887. https://doi.org/10.1097/HJH.0000000000003412
  38. Łoś K., Waszkiewicz N. Biological Markers in Anxiety Disorders. J Clin Med. 2021; 10(8): 1744. https://doi.org/10.3390/jcm10081744
  39. Bosch J.A., Veerman E.C., de Geus E.J. et al. α-Amylase as a reliable and convenient measure of sympathetic activity: Don’t start salivating just yet! Psychoneuroendocrinology. 2011; 36(4): 449–453. https://doi.org/10.1016/j.psyneuen.2010.12.019
  40. Thieux M., Guyon A., Seugnet L. et al. Salivary α-amylase as a marker of sleep disorders: A theoretical review. Sleep Med Rev. 2024; 74: 101894. https://doi.org/10.1016/j.smrv.2023.101894
  41. Engeland C.G., Bosch J.A., Rohleder N. Salivary biomarkers in psychoneuroimmunology. Curr Opin Behav Sci. 2019; 28: 58–65. https://doi.org/10.1016/j.cobeha.2019.01.007
  42. Chojnowska S., Ptaszyńska-Sarosiek I., Kępka A. et al. Salivary Biomarkers of Stress, Anxiety and Depression. J Clin Med. 2021; 10(3): 517. https://doi.org/10.3390/jcm10030517
  43. O’Leary E.D., Howard S., Hughes B.M. et al. Salivary α-amylase reactivity to laboratory social stress with and without acute sleep restriction. Journal of Psychophysiology. 2015; 29(2): 55–63. https://psycnet.apa.org/doi/10.1027/0269-8803/a000134
  44. Tank A.W., Lee Wong D. Peripheral and central effects of circulating catecholamines. Compr Physiol. 2015; 5(1): 1–15. https://doi.org/10.1002/cphy.c140007
  45. Cabib S., Puglisi-Allegra S. The mesoaccumbens dopamine in coping with stress. Neurosci Biobehav Rev. 2012; 36(1): 79–89. https://doi.org/10.1016/j.neubiorev.2011.04.012
  46. Ja-Hyun Baik. Stress and the dopaminergic reward system. Exp Mol Med. 2020; 52(12): 1879–1890. https://doi.org/10.1038/s12276-020-00532-4
  47. Nenezic N., Kostic S., Strac D.S. et al. Dehydroepiandrosterone (DHEA): Pharmacological Effects and Potential Therapeutic Application. Mini-Reviews in Medicinal Chemistry. 2023; 23(8): 941–952. http://dx.doi.org/10.2174/1389557522666220919125817
  48. Ahmed T., Qassem M., Kyriacou P.A. Measuring stress: a review of the current cortisol and dehydroepiandrosterone (DHEA) measurement techniques and considerations for the future of mental health monitoring. Stress. 2023; 26(1): 29–42. https://doi.org/10.1080/10253890.2022.2164187
  49. van Zuiden M., Haverkort S.Q., Tan Z. et al. DHEA and DHEA-S levels in posttraumatic stress disorder: A meta-analytic review. Psychoneuroendocrinology. 2017; 84: 76–82. https://doi.org/10.1016/j.psyneuen.2017.06.010
  50. Lennartsson A.K., Arvidson E., Börjesson M. et al. DHEA-S production capacity in relation to perceived prolonged stress. Stress. 2022; 25(1): 105–112. https://doi.org/10.1080/10253890.2021.2024803
  51. Dutheil F., de Saint Vincent S., Pereira B. et al. DHEA as a Biomarker of Stress: A Systematic Review and Meta-Analysis. Front Psychiatry. 2021; 12: 688367. https://doi.org/10.3389/fpsyt.2021.688367
  52. Asadikaram G., Khaleghi E., Sayadi, A. et al. Assessment of hormonal alterations in major depressive disorder: A clinical study. PsyCh Journal. 2019; 8(4): 423–430. https://doi.org/10.1002/pchj.290
  53. Mazgelytė E., Chomentauskas G., Dereškevičiūtė E. et al. Association of salivary steroid hormones and their ratios with time-domain heart rate variability indices in healthy individuals. J Med Biochem. 2021; 40(2): 173–180. https://doi.org/10.5937/jomb0-26045
  54. O’Connor D.B., Thayer J.F., Vedhara K. Stress and health: a review of psychobiological processes Annu. Rev. Psychol. 2021; 72(1): 663–688. https://doi.org/10.1146/annurev-psych-062520-122331



Creative Commons License
The content is available under the Creative Commons Attribution 4.0 License.

©


This is an open article under the CC BY 4.0 license. Published by the National Medical Research Center for Rehabilitation and Balneology.