A review of association between serum cortisol levels and cognitive performance under stress conditions

Huurun Ein Arifin; Batrisyia Qistina Basharudin; Nik Nor Eizwanie Binti Nik Yusof

Authors

Huurun Ein Arifin Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia
Batrisyia Qistina Basharudin Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia
Nik Nor Eizwanie Binti Nik Yusof Faculty of Pharmacy, University Sultan Zainal Abidin, Terengganu, Malaysia

Keywords:

Adrenal Cortex Hormones; Adult; Cognition; Cognitive Dysfunction; Cortisol; Humans; Hydrocortisone; Meta-Analysis; Neuropsychological Tests; Stress, Psychological.

Abstract

Stress is a physical, mental or emotional response from the human body to changes or challenges. Cortisol levels and cognitive function have played crucial roles in stress management. In this study, a meta-analysis was conducted to review the interaction between serum cortisol levels and cognitive function under stress conditions. We used PubMed, Scopus and Google Scholar to identify reference articles in the past 8 years regarding serum cortisol level and cognitive performance data. There are a variety of stress conditions that were evaluated, such as anxiety, depression, pregnant women, military servicemen, and other situations. Additionally, the cognitive performance was evaluated using Mini-Mental State Examination (MSSE), Wechsler Adult Intelligence Scale (WAIS), Bayley Scales mental development index (MDI), and other cognitive performance measurements. In a total of 35 articles, during stress conditions, we identified an increase of cortisol levels while the cognitive performance was impaired. We hypothesised that the stress condition would increase the serum cortisol level and that the cortisol would delay cognitive performance.

References

Villines Z. Eustress vs. distress: What is the difference? Medical News Today. 2022 May 19. https://www.medicalnewstoday.com/articles/eustress-vs-distress

Lu S, Wei F, Li G. The evolution of the concept of stress and the framework of the stress system. Cell Stress. 2021;5(6):76–85. https://doi.org/10.15698/cst2021.06.250

Schwabe L, Hermans EJ, Joëls M, Roozendaal B. Mechanisms of memory under stress. Neuron. 2022;110(9):1450–1467. https://doi.org/10.1016/j.neuron.2022.02.020

Chrousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol. 2009;5(7):374–381. https://doi.org/10.1038/nrendo.2009.106

James KA, Stromin JI, Steenkamp N, Combrinck MI. Understanding the relationships between physiological and psychosocial stress, cortisol and cognition. Front Endocrinol. 2023;14:1085950. https://doi.org/10.3389/fendo.2023.1085950

Knezevic E, Nenic K, Milanovic V, Knezevic NN. The role of cortisol in chronic stress, neurodegenerative diseases, and psychological disorders. Cells. 2022;12(23):2726. https://doi.org/10.3390/cells12232726

Watson S. What Is Cortisol? HealthCentral. 2022 Jan 13. https://www.healthcentral.com/condition/cushings-syndrome/what-is-cortisol

Thau L, Gandhi J, Sharma S. Physiology, Cortisol. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Aug 28. https://www.ncbi.nlm.nih.gov/books/NBK538239/

Michels A, Michels N. Addison disease: early detection and treatment principles. Am Fam Physician. 2014;89(7):563-568. https://pubmed.ncbi.nlm.nih.gov/24695602/

Huecker MR, Bhutta BS, Dominique E. Adrenal Insufficiency. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Aug 17. https://www.ncbi.nlm.nih.gov/books/NBK441832/

Echouffo-Tcheugui JB, Conner SC, Himali JJ, Maillard P, DeCarli CS, Beiser AS, et al. Circulating cortisol and cognitive and structural brain measures. Neurology. 2018;91(21):e1961–e1970. https://doi.org/10.1212/wnl.0000000000006549

Turpeinen U, Hämäläinen E. Determination of cortisol in serum, saliva and urine. Best Pract Res Clin Endocrinol Metab. 2013;27(6):795–801. https://doi.org/10.1016/j.beem.2013.10.008

Cai Y, Ren L, Tan S, Liu X, Li C, Gang X, et al. Mechanism, diagnosis, and treatment of cyclic Cushing’s syndrome: A review. Biomed Pharmacother. 2022;153:113301. https://doi.org/10.1016/j.biopha.2022.113301

Hinds JA, Sanchez ER. The Role of the Hypothalamus–Pituitary–Adrenal (HPA) Axis in Test-Induced Anxiety: Assessments, Physiological Responses, and Molecular Details. Stresses. 2022;2(1):146–155. https://doi.org/10.3390/stresses2010011

Mbiydzenyuy NE, Qulu LA. Stress, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, and aggression. Metab Brain Dis. 2024;39(8):1613–1636. https://doi.org/10.1007/s11011-024-01391-7

Caldwell JA, Niro PJ, Farina EK, McClung JP, Caron GR, Lieberman HR. A Z-score based method for comparing the relative sensitivity of behavioral and physiological metrics. PLoS One. 2019;14(8):e0220749. https://doi.org/10.1371/journal.pone.0220749

Anjum A, Anwar H, Sohail MU, Ali Shah SM, Hussain G, Rasul A, et al. The association between serum cortisol, thyroid profile, and anthropometric parameters of undergraduate students under examination stress. Eur J Inflamm. 2021;25. https://doi.org/10.1177/20587392211000884

Varanoske AN, Wells AJ, Kozlowski GJ, Gepner Y, Frosti CL, Boffey D, et al. Effects of β-alanine supplementation on physical performance and endocrine function during a 24 h simulated military operation. Physiol Rep. 2018;6(24):e13938. https://doi.org/10.14814/phy2.13938

Noushad S, Sajid U, Ahmed S, Ansari B. Assessment of Cortisol, Brain-Derived Neurotropic factor, C - reactive protein, Interleukin-6 levels and cognitive decline after trauma exposure. Ann Psychophysiol. 2021;8(1):06-14.

Bermejo JL, Ribeiro B, Marco-Ahulló A, Villarrasa-Sapiña I, Garcia-Masso X. Increased cortisol levels caused by acute resistance physical exercise impair memory and learning ability. PeerJ. 2022;10:e13000. https://doi.org/10.7717/peerj.13000

Pan C, Cao Y, Ge J, Li Y, Feng W, Yan J, et al. Mediation on the association between HPA axis hyperactivity and cognitive impairment by abnormal hippocampal function. J Affect Disord. 2025;382:39–47. https://doi.org/10.1016/j.jad.2025.04.055

Shao Z, Zikereya T, Peng J, Luo M, Chen J, Shi K. Comparative study on the effects of different types of acute exercise on cortisol levels and cognitive functions. [Preprint]. 2024. https://doi.org/10.1101/2024.09.14.613054

Torbati AG, Nejat H, Toozandehjani H, Samari AA, Akbari Amarghan H. Effect of Compassion-Focused Therapy (CFT) on Blood Cortisol and Cognitive-Emotion Regulation in Drug Abusers. Jundishapur J Health Sci. 2020;12(1):e100148. https://doi.org/10.5812/jjhs.100148

Baliyan S, Cimadevilla JM, De Vidania S, Pulopulos MM, Sandi C, Venero C. Differential Susceptibility to the Impact of the COVID-19 Pandemic on Working Memory, Empathy, and Perceived Stress: The Role of Cortisol and Resilience. Brain Sci. 2021;11(3):348. https://doi.org/10.3390/brainsci11030348

Lieberman HR, Farina EK, Caldwell J, Williams KW, Thompson LA, Niro PJ, et al. Cognitive function, stress hormones, heart rate and nutritional status during simulated captivity in military survival training. Physiol Behav. 2016;165:86–97. https://doi.org/10.1016/j.physbeh.2016.06.037

De Oliveira LF, Pessoa T, Fechio JJ, Fernandes JA, Sampaio RC, Vardaris CV, et al. Uric Acid and Cortisol Levels in Plasma Correlate with Pre-Competition Anxiety in Novice Athletes of Combat Sports. Brain Sci. 2022;12(6):712. https://doi.org/10.3390/brainsci12060712

Varanoske AN, McClung HL, Sepowitz JJ, Halagarda CJ, Farina EK, Berryman CE, et al. Stress and the gut-brain axis: Cognitive performance, mood state, and biomarkers of blood-brain barrier and intestinal permeability. Brain Behav Immun. 2022;101:383-393. https://doi.org/10.1016/j.bbi.2022.02.002

Becker L, Rohleder N. Associations between Attention and Implicit Associative Learning in Healthy Adults: The Role of Cortisol and Salivary Alpha-Amylase Responses to an Acute Stressor. Brain Sci. 2020;10(8):544. https://doi.org/10.3390/brainsci10080544

Forse JN, Beckner ME, Giles GE, Brunyé TT, Eddy MD, Cantelon JA, et al. Psychological, physical, and cognitive factors that influence tactical performance during a military relevant virtual reality scenario. Cogn Res Princ Implic. 2025;10(1):76. https://doi.org/10.1186/s41235-025-00687-6

Brand S, Mikoteit T, Kalak N, Bahmani DS, Lemola S, Gerber M, et al. Cortisol Impacted on Explicit Learning Encoding, but Not on Storage and Retrieval. Front Psychol. 2018;9:2240. https://doi.org/10.3389/fpsyg.2018.02240

José E, Frechette A, Pokhvisneva I, Arcego DM, Barth B, Tejada C, et al. Examining attachment, cortisol secretion, and cognitive neurodevelopment in preschoolers and its predictive value for telomere length at age seven. Front Behav Neurosci. 2022;16:954977. https://doi.org/10.3389/fnbeh.2022.954977

Cintineo HP, Arent SM. Anticipatory Salivary Cortisol and State Anxiety Before Competition Predict Match Outcome in Division I Collegiate Wrestlers. J Strength Cond Res. 2019;33(11):2905–2908. https://doi.org/10.1519/jsc.0000000000003376

La Fratta I, Franceschelli S, Speranza L, Patruno A, Michetti C, Ballerini P, et al. Salivary oxytocin, cognitive anxiety and self-confidence in pre-competition athletes. Sci Rep. 2021;11(1):16877. https://doi.org/10.1038/s41598-021-96392-7

Dziembowska I, Wójcik M, Słomka A, Żekanowska E. Female Volleyball Players Are More Prone to Cortisol Anticipatory Stress Response than Sedentary Women. Medicina (Kaunas). 2019;55(6):258. https://doi.org/10.3390/medicina55060258

Bortolotto I, De Brum APS, Guecheva TN, De Souza LM, De Paula-Ramos ALL, Trindade C, et al. DNA damage, salivary cortisol levels, and cognitive parameters in a nursing team. Mutat Res Genet Toxicol Environ Mutagen. 2020;861-862:503300. https://doi.org/10.1016/j.mrgentox.2020.503300

Gabrys RL, Howell JW, Cebulski SF, Anisman H, Matheson K. Acute stressor effects on cognitive flexibility: mediating role of stressor appraisals and cortisol. Stress. 2019;22(2):182–189. https://doi.org/10.1080/10253890.2018.1494152

Shields MR, Brooks MA, Koltyn KF, Kim JS, Cook DB. Cognitive Resilience and Psychological Responses across a Collegiate Rowing Season. Med Sci Sports Exerc. 2017;49(11):2276–2285. https://doi.org/10.1249/MSS.0000000000001353

Sang YM, Wang LJ, Mao HX, Lou XY, Zhu YJ. The association of short-term memory and cognitive impairment with ghrelin, leptin, and cortisol levels in non-diabetic and diabetic elderly individuals. Acta Diabetol. 2018;55(6):531–539. https://doi.org/10.1007/s00592-018-1111-5

Cullen AE, Addington J, Bearden CE, Stone WS, Seidman LJ, Cadenhead KS, et al. Stressor-Cortisol Concordance Among Individuals at Clinical High-Risk for Psychosis: Novel Findings from the NAPLS Cohort. Psychoneuroendocrinology. 2020;115:104649. https://doi.org/10.1016/j.psyneuen.2020.104649

Alloway TP, Gathercole SE, Kirkwood H, Elliott J. The working memory rating scale: A classroom-based behavioral assessment of working memory. Learn Individ Differ. 2008;19(2):242–245. https://doi.org/10.1016/j.lindif.2008.10.003

Xin Z, Gu S, Yi L, Li H, Wang F. Acute Exposure to the Cold Pressor Stress Impairs Working Memory Functions: An Electrophysiological Study. Front Psychiatry. 2020;11:544540. https://doi.org/10.3389/fpsyt.2020.544540

Hadipour M. The Impacts of Video Games on Cognitive Function and Cortisol Levels in Young Female Volunteers. [Preprint]. Academia.edu; 2019.

Flintoff J, Pattinson C, Ahamed S, Ali S, et al. Investigating associations between BDNF, cortisol, and cognitive performance during psychosocial and heat stress. Int J Neuropsychopharmacol. 2025;28(Suppl 2):ii164–ii165. https://doi.org/10.1093/ijnp/pyaf052.326

Ju Y, Wang M, Lu X, Sun J, Dong Q, Zhang L, et al. The effects of childhood trauma on the onset, severity and improvement of depression: The role of dysfunctional attitudes and cortisol levels. J Affect Disord. 2020;276:402-410. https://doi.org/10.1016/j.jad.2020.07.023

Ngampramuan S, Tungtong P, Mukda S, Jariyavilas A, Sakulisariyaporn C. Evaluation of Autonomic Nervous System, Saliva Cortisol Levels, and Cognitive Function in Major Depressive Disorder Patients. Depress Res Treat. 2018;2018:7343592. https://doi.org/10.1155/2018/7343592

Bertollo AG, Grolli RE, Plissari ME, Gasparin VA, Quevedo J, Réus GZ, et al. Stress and serum cortisol levels in major depressive disorder: A cross-sectional study. AIMS Neurosci. 2020;7(4):459–469. https://doi.org/10.3934/Neuroscience.2020028

Olié E, Guillaume S, Girod C, Cazals A, Chaudieu I, Courtet P. Dexamethasone Suppression Test May Predict More Severe/Violent Suicidal Behavior. Front Psychiatry. 2020;11:499211. https://doi.org/10.3389/fpsyt.2020.00097

Zhong X, Ning Y, Gu Y, Wu Z, Ouyang C, Liang W, et al. A reliable global cognitive decline and cortisol as an associated risk factor for patients with late-life depression in the short term: A 1-year prospective study. J Affect Disord. 2018;240:214-219. https://doi.org/10.1016/j.jad.2018.07.052

Chu B, Marwaha K, Sanvictores T, Awosika AO, Ayers D. Physiology, Stress Reaction. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK541120/

Scott TJM, Dickson JM. Effects of acute stress on executive functions in depression, generalised anxiety and borderline personality disorder. J Affect Disord Rep. 2025;20:100917. https://doi.org/10.1016/j.jadr.2025.100917

Ahmed F, Dubey DK, Garg R, Srivastava R. Effects of examination-induced stress on memory and blood pressure. J Family Med Prim Care. 2023;12(11):2757–2762. https://doi.org/10.4103/jfmpc.jfmpc_774_23

Bremner JD. Traumatic stress: effects on the brain. Dialogues Clin Neurosci. 2006;8(4):445–461. https://doi.org/10.31887/DCNS.2006.8.4/jbremner

Pulopulos MM, Baeken C, De Raedt R. Cortisol response to stress: The role of expectancy and anticipatory stress regulation. Horm Behav. 2020;117:104587. https://doi.org/10.1016/j.yhbeh.2019.104587

Ahmed F, Dubey DK, Garg R, Srivastava R. Effects of examination-induced stress on memory and blood pressure. J Fam Med Prim Care. 2023;12(11):2757–62. https://doi.org/10.4103/jfmpc.jfmpc_840_23

Zhong X, Ning Y, Gu Y, Wu Z, Ouyang C, Liang W, et al. A reliable global cognitive decline and cortisol as an associated risk factor for patients with late-life depression in the short term: A 1-year prospective study. J Affect Disord. 2018;240:214–9. https://doi.org/10.1016/j.jad.2018.07.037

Ngampramuan S, Tungtong P, Mukda S, Jariyavilas A, Sakulisariyaporn C. Evaluation of Autonomic Nervous System, Saliva Cortisol Levels, and Cognitive Function in Major Depressive Disorder Patients. Depress Res Treat. 2018;2018:7343592. https://doi.org/10.1155/2018/7343592

Bremner JD. Traumatic stress: effects on the brain. Dialogues Clin Neurosci. 2006;8(4):445–61. https://doi.org/10.31887/DCNS.2006.8.4/jbremner

Pulopulos MM, Baeken C, De Raedt R. Cortisol response to stress: The role of expectancy and anticipatory stress regulation. Horm Behav. 2020;117:104587. https://doi.org/10.1016/j.yhbeh.2019.104587

Echouffo-Tcheugui JB, Conner SC, Himali JJ, Maillard P, DeCarli CS, Beiser AS, et al. Circulating cortisol and cognitive and structural brain measures. Neurology. 2018;91(21):e1961–71. https://doi.org/10.1212/WNL.0000000000006549

Bertollo AG, Grolli RE, Plissari ME, Gasparin VA, Quevedo J, Réus GZ, et al. Stress and serum cortisol levels in major depressive disorder: a cross-sectional study. AIMS Neurosci. 2020;7(4):459–69. https://doi.org/10.3934/Neuroscience.2020026