Clinical relevance of stress biomarkers as health-disease indicators

Keywords: Psychophysiology, psychological stress, autonomic regulation, stress response, physiological markers


Stress is a protective mechanism inherent in living organisms. In humans, it fulfils an adaptive function, capable of generating responses at different levels: physiological, metabolic, endocrine, cognitive, among others. Constant exposure to stressful events or stimuli is capable of exceeding the person's resources, causing discomfort and progressively wearing down health. Recently, a significant increase in stress-associated diseases has been observed. The consequences of this problem are multiple; personal, socioeconomic, and professional difficulties. Current evidence shows that daily stress will tend to increase in the upcoming years, affecting the quality of life and mental health of the population in general. Both environmental and natural factors as well as the economic and social repercussions derived from the current pandemic tend to further aggravate this problem. Given this scenario, developing strategies that promote mental health and the prevention of its associated pathologies is a priority. One way to develop more effective intervention programs is through the use of biomarkers, many of which show high diagnostic sensitivity and specificity, and which represent a wide interest within the clinical area and psychotherapeutic intervention. The objective of this article is to make a general review of the main biomarkers used in clinical practice, as well as potential biomarkers that allow the identification of early signs of health problems related to mental stress in a more efficient and accessible way.


Download data is not yet available.


Gianaros PJ, Jennings JR. Host in the machine: A neurobiological perspective on psychological stress and cardiovascular disease. Am. Psychol. 2018;73(8):1031–44.

Iob E, Steptoe A. Cardiovascular disease and hair cortisol: A novel biomarker of chronic stress. Curr. Cardiol. Rep. 2019;21(10):116.

Toohey K, Pumpa K, McKune A, Cooke J, Welvaert M, Northey J, et al. The impact of high-intensity interval training exercise on breast cancer survivors: a pilot study to explore fitness, cardiac regulation and biomarkers of the stress systems. BMC. Cancer. 2020;20(1):787.

Poplawski J, Radmilovic A, Montina TD, Metz GAS. Cardiorenal metabolic biomarkers link early life stress to risk of non-communicable diseases and adverse mental health outcomes. Sci. Rep. 2020;10(1):13295.

The A-F, Reijmerink I, van der Laan M, Cnossen F. Heart rate variability as a measure of mental stress in surgery: a systematic review. Int. Arch. Occup. Environ. Heal. 2020;93(7):805–21.

Zamkah A, Hui T, Andrews S, Dey N, Shi F, Sherratt RS. Identification of suitable biomarkers for stress and emotion detection for future personal affective wearable sensors. Biosens. 2020;10(4):40.

Hagen E, Erga AH, Hagen KP, Nesvåg SM, McKay JR, Lundervold AJ, et al. One-year sobriety improves satisfaction with life, executive functions and psychological distress among patients with polysubstance use disorder. J. Subst. Abus. Treat. 2017;76:81–7.

Soder HE, Wardle MC, Schmitz JM, Lane SD, Green C, Vujanovic AA. Baseline resting heart rate variability predicts post-traumatic stress disorder treatment outcomes in adults with co-occurring substance use disorders and post-traumatic stress. Psychophys. 2019;56(8).

D’Souza MA JM, Wardle M, Green CE, Lane SD, Schmitz JM, Vujanovic AA. Resting heart rate variability: Exploring associations with symptom severity in adults with substance use disorders and posttraumatic stress. J. Dual. Diagn. 2019;15(1):2–7.

Benson S, Ayre E, Garrisson H, Wetherell MA, Verster JC, Scholey A. Alcohol hangover and multitasking: Effects on mood, cognitive performance, stress reactivity, and perceived effort. J. Clin. Med. 2020;9(4):1154.

González E, Arias F, Szerman N, Vega P, Mesias B, Basurte I. Coexistence between personality disorders and substance use disorder. Madrid study about prevalence of dual pathology. Actas. Esp. Psiquiatr. 2019;47(6):218–28.

Daviu N, Bruchas MR, Moghaddam B, Sandi C, Beyeler A. Neurobiological links between stress and anxiety. Neurobiol. Stress. 2019;11(100191):100191.

Bremner JD, Moazzami K, Wittbrodt MT, Nye JA, Lima BB, Gillespie CF, et al. Diet, stress and mental health. Nutrients. 2020;12(8):2428.

Michels N, Matthys D, Thumann B, Marild S, De Henauw S. Children’s stress-related reports and stress biomarkers interact in their association with metabolic syndrome risk. Stress. Heal. 2018;34(4):523–33.

Jonsdottir IH, Sjörs Dahlman A. Endocrine and immunological aspects of burnout: a narrative review. Eur. J. Endocrinol. 2019;180(3):147–158.

Pozzato I, Craig A, Gopinath B, Tran Y, Dinh M, Gillett M, et al. Biomarkers of autonomic regulation for predicting psychological distress and functional recovery following road traffic injuries: protocol for a prospective cohort study. BMJ. Open. 2019;9(4):e024391.

Dhama K, Latheef SK, Dadar M, Samad HA, Munjal A, Khandia R, et al. Biomarkers in stress related diseases/disorders: Diagnostic, prognostic, and therapeutic values. Front. Mol. Biosci. 2019;6:91.

Cantus DS, López NS, Ballester MC, Gómez SS, de la Rubia Ortíz JE. El estrés en la enfermedad de Parkinson: Biomarcadores cortisol y amilasa. Revisión sistemática. Rev. Cient. Soc. Esp. Enferm. Neurol. 2019;(50):12–22.

Allen TM, Struemph KL, Toledo-Tamula MA, Wolters PL, Baldwin A, Widemann B, et al. The Relationship Between Heart Rate Variability, Psychological Flexibility, and Pain in Neurofibromatosis Type 1. Pain. Pract. 2018;18(8):969–78.

Lo EWV, Wei YH, Hwang BF. Association between occupational burnout and heart rate variability: A pilot study in a high-tech company in Taiwan. Med. (United States). 2020;99(2):1–11.

Pribék IK, SzH ucs KF, Süle M, Grosz G, Ducza E, Vigh D, et al. Detection of acute stress by smooth muscle electromyography: A translational study on rat and human. Life. Sci. 2021;277(119492):119492.

Park J, Ross A, Klagholz SD, Bevans MF. The role of biomarkers in research on caregivers for cancer patients: A scoping review. Biol. Res. Nurs. 2018;20(3):300–11.

Hernández-Ceruelos A, Vázquez-Alvarado P, Pelallo-Martínez N, Muñoz-Juárez S. Bioindicators and Biomarkers. Mex. J. Med. Res. 2013;1(2).

Condon EM. Chronic stress in children and adolescents: A review of biomarkers for use in pediatric research. Biol. Res. Nurs. 2018;20(5):473–96.

Arango V SS. Biomarcadores para la evaluación de riesgo en la salud humana. Rev. Fac. Nac. Sal. Púb. 2012;30(1):75–82.

Fossion R, Rivera AL, Estañol B. A physicist’s view of homeostasis: how time series of continuous monitoring reflect the function of physiological variables in regulatory mechanisms. Physiol. Meas. 2018;39(8):84007.

Cozma S, Dima-Cozma LC, Ghiciuc CM, Pasquali V, Saponaro A, Patacchioli FR. Salivary cortisol and α-amylase: subclinical indicators of stress as cardiometabolic risk. Braz. J. Med. Biol. Res. 2017;50(2):e5577.

Lee DY, Kim E, Choi MH. Technical and clinical aspects of cortisol as a biochemical marker of chronic stress. BMB. Rep. 2015;48(4):209–16.

Lengacher CA, Reich RR, Paterson CL, Shelton M, Shivers S, Ramesar S, et al. A large randomized trial: Effects of mindfulness-based stress reduction (MBSR) for breast cancer (BC) survivors on salivary cortisol and IL-6. Biol. Res. Nurs. 2019;21(1):39–49.

Eddington HS, McLeod M, Trickey AW, Barreto N, Maturen K, Morris AM. Patient-reported distress and age-related stress biomarkers among colorectal cancer patients. Canc. Med. 2021;10(11):3604–12.

Rangel Granados ES. Los marcadores psicofisiológicos. Dando certeza al fenómeno psicológico. Bol. Cient. Esc. Super. Ato. Tula. 2017;4(8).

Pulopulos MM, Vanderhasselt MA, De Raedt R. Association between changes in heart rate variability during the anticipation of a stressful situation and the stress-induced cortisol response. Psychoneuroendocri. 2018;94:63–71.

Woody A, Hamilton K, Livitz IE, Figueroa WS, Zoccola PM. Buccal telomere length and its associations with cortisol, heart rate variability, heart rate, and blood pressure responses to an acute social evaluative stressor in college students. Stress. 2017;20(3):249–57.

Egawa M, Haze S, Gozu Y, Hosoi J, Onodera T, Tojo Y, et al. Evaluation of psychological stress in confined environments using salivary, skin, and facial image parameters. Sci. Rep. 2018;8(1):8264.

Hovland A, Pallesen S, Hammar Å, Hansen AL, Thayer JF, Tarvainen MP, et al. The relationships among heart rate variability, executive functions, and clinical variables in patients with panic disorder. Int. J. Psychophysiol. 2012;86(3):269–75.

Thayer JF, Hansen AL, Saus-Rose E, Johnsen BH. Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health. Ann. Behav. Med. 2009;37(2):141–53.

Thayer JF, Lane RD. A model of neurovisceral integration in emotion regulation and dysregulation. J. Affect. Disord. 2000 Dec 2;61(3):201–16.

Laborde S, Mosley E, Thayer JF. Heart Rate Variability and Cardiac Vagal Tone in Psychophysiological Research – Recommendations for Experiment Planning, Data Analysis and Data Reporting. Front. Psychol. 2017;8:213.

Järvelin-Pasanen S, Sinikallio S, Tarvainen MP. Heart rate variability and occupational stress-systematic review. Ind. Heal. 2018;56(6):500–11.

Koerten HR, Watford TS, Dubow EF, O’Brien WH. Cardiovascular effects of brief mindfulness meditation among perfectionists experiencing failure. Psychophys. 2020;57(4):e13517.

Thayer JF, Ahs F, Fredrikson M, Sollers 3rd JJ, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci. Biobehav. Rev. 2012;36(2):747–56.

Mann SL, Selby EA, Bates ME, Contrada RJ. Integrating affective and cognitive correlates of heart rate variability: A structural equation modeling approach. Int. J. Psychophysiol. 2015;98(1):76–86.

Hamilton JL, Alloy LB. Atypical reactivity of heart rate variability to stress and depression across development: Systematic review of the literature and directions for future research. Clin. Psychol. Rev. 2016;50:67–79

Hildebrandt LK, Mccall C, Engen HG, Singer T. Cognitive flexibility, heart rate variability, and resilience predict fine-grained regulation of arousal during prolonged threat. Psychophysiol. 2016;53(6):880–90.

Schaub C, Von Gunten A, Morin D, Wild P, Gomez P, Popp J. The effects of hand massage on stress and agitation among people with dementia in a hospital setting: A pilot study. Appl. Psychophysiol. Biofeedback. 2018;43(4):319–32.

van der Zwan JE, de Vente W, Huizink AC, Bögels SM, de Bruin EI. Physical activity, mindfulness meditation, or heart rate variability biofeedback for stress reduction: a randomized controlled trial. Appl. Psychophysiol. Biofeedback. 2015;40(4):257–68.

Abbing A, de Sonneville L, Baars E, Bourne D, Swaab H. Anxiety reduction through art therapy in women. Exploring stress regulation and executive functioning as underlying neurocognitive mechanisms. PLoS. One. 2019;14(12):e0225200.

Lopes-Júnior LC, Bomfim E, Olson K, Neves ET, Silveira DSC, Nunes MDR, et al. Effectiveness of hospital clowns for symptom management in paediatrics: systematic review of randomised and non-randomised controlled trials. BMJ. 2020;371:m4290.

How to Cite
Morales-López, C. A. (2022). Clinical relevance of stress biomarkers as health-disease indicators. Mexican Journal of Medical Research ICSA, 10(20), 34-43.