Psychosocial Stress and Biomarkers

???? Dr. Marc Dellière

???? Dr. Emmanuelle Cart-Tanneur - Eurofins-Biomnis

During stress, physiological and endocrine alterations, disturbances in functional systems (e.g., clinical parameters), biochemical (e.g., hormones), and metabolic pathways become inevitable, leading to alterations in metabolic biomarkers (metabolites, enzymes, hormones).

?? This cascade influences other vital early response systems (e.g., cardiovascular, central nervous, renal) and late response systems (e.g., hepatobiliary, pancreatic). Consequently, this results in multisystem involvement and a generalized disruption of a range of biomarkers specific to each system or organ.

?? Stress levels can be monitored through the measurement of biomarkers, which play a crucial role in the prognosis of stress-related diseases and disorders and in therapeutic guidance.

?? PHYSIOLOGICAL PARAMETERS, such as respiratory rate, heart rate, blood pressure, and central body temperature, are the most commonly observed markers describing environmental, social, and psychological stress.

?? Heart Rate Variability (HRV) measurement has now become an essential marker of stress. While heart rate focuses on the frequency of contractions, HRV focuses on the interval between two heartbeats. A more or less regular pattern reflects an adaptive capacity that diminishes notably during stress and also with age.

??Classic STRESS MARKERS also include endocrine changes, especially in hormone levels such as cortisol and adrenaline.

??Physiological biomarkers of chronic stress: A systematic review.

Noushad S, et al. Int J Health Sci (Qassim). 2021. PMID: 34548863

??Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

l Biosci. 2019 Oct 18;6:91. doi: 10.3389/fmolb.2019.00091. eCollection 2019.

?In my practice, to assess stress, I look for various parameters offered notably by Biomnis Eurofins Juvenalis laboratories.

-Salivary or serum CORTISOL

-Cortisol/DHEA-S Ratio, very important for determining the severity of stress (DHEA-S sulfate of dehydroepiandrosterone).

??Cortisol and DHEA-S are associated with startle potentiation during aversive conditioning in humans.

Grillon C, Pine DS, Baas JM, Lawley M, Ellis V, Charney DS.Psychopharmacology (Berl). 2006 Jun;186(3):434-41. doi: 10.1007/s00213-005-0124-2.

??Associations between job strain and the cortisol/DHEA-S ratio among management and nonmanagement personnel.

Gadinger MC, Loerbroks A, Schneider S, Thayer JF, Fischer JE. Psychosom Med. 2011 Jan;73(1):44-52. doi: 10.1097/PSY.0b013e3181fc6fe8.

-The Cortisol Awakening Response (CAR), feasible through 2 saliva samples, evaluates adrenal response upon awakening by measuring the rise in cortisol levels 30 minutes after waking compared to baseline levels.

-Serum Magnesium, although its measurement only provides imperfect information on magnesium status. In some cases, exploring thyroid function may be interesting.

-Free triiodothyronine (Free T3 or FT3), a thyroid hormone whose levels depend closely on the conversion of free T4, participates in regulating numerous metabolic reactions (cardiac, muscular, nervous, and digestive activity).

-Additionally, Vitamin D, a major parameter due to its multiple implications (bone and joint health, immunity, inflammation, mood, cognition).

?? OXIDATIVE STRESS

Psychosocial stress generates OXIDATIVE STRESS, making an Oxidative Stress Assessment interesting. Numerous pathological processes are direct or indirect consequences of oxidative stress, reflecting dysfunction in mechanisms normally responsible for its control.

- Copper and zinc, cofactors for more than 300 enzymes, are particularly involved in antioxidant defenses and immune support. Their imbalance (ideally equal to 1) serves as a marker of oxidative stress.

- Selenium, important for antioxidant protection and proper synthesis of thyroid hormones, is a cofactor for glutathione peroxidase (GPX), closely linked to its levels.

- High-sensitivity C-reactive protein (CRP) indicates low-grade inflammation, with well-described links to oxidative stress.

- Uric acid, while not strictly an antioxidant, has intrinsic antioxidant properties.

- Oxidized LDL represents the end product of oxidative stress on lipids.

- The ratio between glutathione peroxidase (GPX) and glutathione reductase (GR) reflects the balance between reduced and oxidized glutathione, indicating oxidative stress processes.

Juvenalis Biomnis-specific index, calculated from 9 parameters selected for their statistical relevance, offers a highly precise assessment of oxidative stress, providing avenues for possible management. This choice also simplifies pre-analytics, ensuring feasibility of the assessment along with diagnostic contribution to oxidative stress.

?? Additionally, vitamins A, C, and E, superoxide dismutase (SOD), and Coenzyme Q10, the body's main antioxidant, are worth considering. However, Coenzyme Q10 deficiency, while not exceptional, should not be considered a marker of oxidative stress.

??Psychosocial work environment and oxidative stress among nurses.

Salem EA, Ebrahem SM.J Occup Health. 2018 Mar 27;60(2):182-191. doi: 10.1539/joh.17-0186-OA.

??Childhood psychosocial stress is linked with impaired vascular endothelial function, lower SIRT1, and oxidative stress in young adulthood.

Jenkins NDM, Rogers EM, Banks NF, Tomko PM, Sciarrillo CM, Emerson SR, Taylor A, Teague TK.Am J Physiol Heart Circ Physiol. 2021 Sep 1;321(3):H532-H541. doi: 10.1152/ajpheart.00123.2021.

??Association of acute psychosocial stress with oxidative stress: Evidence from serum analysis.

Kim E, Zhao Z, Rzasa JR, Glassman M, Bentley WE, Chen S, Kelly DL, Payne GF.Redox Biol. 2021 Nov;47:102138. doi: 10.1016/j.redox.2021.102138.

?? LOW-GRADE INFLAMMATION

Psychosocial stress inducing LOW-GRADE INFLAMMATION makes Low-Grade Inflammation Assessment relevant.

- Highly sensitive CRP, elevated in low-grade inflammation, particularly arterial wall inflammation linked to heart attacks. Additionally, stress is associated with neuroinflammation.

- Erythrocyte fatty acids, major components of cell membranes and regulators of the inflammatory response, evaluate the impact of lipid intake on the omega-6/omega-3 polyunsaturated fatty acid balance, crucial for structural and anti-inflammatory organism homeostasis. This can also identify a pro-inflammatory state through the AA/EPA ratio, signaling increased risk.

- Homocysteine, crucial for cellular methylation processes, with elevated levels indicating vascular inflammatory alerts due to deficiencies in vitamins B6, B9, or B12.

??Stimulation of systemic low-grade inflammation by psychosocial stress. Rohleder N.Psychosom Med. 2014 Apr;76(3):181-9. doi: 10.1097/PSY.0000000000000049.

??Low-grade systemic inflammation and the workplace. Viljoen M, Thomas Neé Negrao BL.Work. 2021;69(3):903-915. doi: 10.3233/WOR-213523.

??Psychosocial stressors at work and inflammatory biomarkers: PROspective Quebec Study on Work and Health. Duchaine CS, Brisson C, Talbot D, Gilbert-Ouimet M, Trudel X, Vézina M, Milot A, Diorio C, Ndjaboué R, Giguère Y, Masse B, Dionne CE, Maunsell E, Laurin D.Psychoneuroendocrinology. 2021 Nov;133:105400. doi: 10.1016/j.psyneuen.2021.105400.

?? INTESTINAL BARRIER

Psychosocial stress can alter the intestinal barrier at various levels, leading to MICROBIOTA DYSBIOSIS, INTESTINAL HYPERPERMEABILITY (leaky gut), and INTESTINAL INFLAMMATION. Interestingly, these elements are closely related and regulate each other.

An intestinal hyperpermeability assessment may include:

- Casein IgG, indicating intestinal epithelium integrity. It helps rule out leaky gut hypothesis when normal.

- Intestinal microbiota, consisting of trillions of bacteria, viruses, and fungi in the gut, protects and strengthens immune defenses if well-balanced. Predominance of harmful bacteria can lead to dysbiosis, causing certain inflammatory diseases.

- Fecal zonulin, a functional indicator of intestinal permeability.

??Psychological Stress, Intestinal Barrier Dysfunctions, and Autoimmune Disorders: An Overview.

Ilchmann-Diounou H, Menard S.Front Immunol. 2020 Aug 25;11:1823. doi: 10.3389/fimmu.2020.01823.

??Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism.

Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelingen C, Verschueren S, Houben E, Salim Rasoel S, T?th J, Holvoet L, Farré R, Van Oudenhove L, Boeckxstaens G, Verbeke K, Tack J.Gut. 2014 Aug;63(8):1293-9. doi: 10.1136/gutjnl-2013-305690.