{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:41:49Z","timestamp":1792078909715,"version":"4.4.0"},"reference-count":116,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Anxiety and depression are highly prevalent mental health disorders often associated with dysregulation of neuroendocrine and immune systems, particularly the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis and the sympathetic\u2013adrenal\u2013medullary (SAM) system. Recent research highlights the potential of salivary biomarkers to serve as non-invasive indicators for psychological distress. This narrative review synthesizes current evidence on key salivary biomarkers, cortisol, alpha-amylase (sAA), secretory immunoglobulin A (sIgA), chromogranin A (CgA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u03b1), C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF), and salivary microRNAs (miRNAs), in relation to anxiety, depression, and stress. A comprehensive literature search (2010\u20132025) was conducted using multiple databases and relevant MeSH terms. The review reveals consistent associations between these salivary analytes and stress-related disorders, reflecting changes in neuroendocrine activity, immune response, and neuroplasticity. Cortisol and sAA mirror acute stress reactivity, while cytokines and CRP indicate chronic inflammation. BDNF and miRNAs provide insight into neuroplastic dysfunction and gene regulation. Despite promising results, limitations such as variability in sampling methods and biomarker specificity remain. In conclusion, salivary biomarkers offer a promising avenue for early detection, monitoring, and personalization of treatment in mood and anxiety disorders. Conclusions: Cortisol and alpha-amylase serve as the principal markers of acute stress response, whereas cytokines such as IL-6 and TNF-\u03b1, together with CRP, indicate chronic inflammation associated with extended emotional distress.<\/jats:p>","DOI":"10.3390\/cimb47070488","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:53:13Z","timestamp":1750917193000},"page":"488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Salivary Biomarkers as a Predictive Factor in Anxiety, Depression, and Stress"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2312-6987","authenticated-orcid":false,"given":"Dana Gabriela","family":"Budala","sequence":"first","affiliation":[{"name":"Department of Dentures, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-9672","authenticated-orcid":false,"given":"Ionut","family":"Luchian","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos Ioan","family":"Virvescu","sequence":"additional","affiliation":[{"name":"Department of Dental Materials, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teona","family":"Tudorici","sequence":"additional","affiliation":[{"name":"Department of Dentures, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Constantin","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinovia","family":"Surlari","sequence":"additional","affiliation":[{"name":"Department of Fixed Prosthodontics, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7404-399X","authenticated-orcid":false,"given":"Oana","family":"Butnaru","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan Nicolae","family":"Bosinceanu","sequence":"additional","affiliation":[{"name":"Department of Dentures, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0319-0538","authenticated-orcid":false,"given":"Cosmin","family":"Bida","sequence":"additional","affiliation":[{"name":"Department of Dentures, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Hancianu","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12325-021-01859-8","article-title":"Generalised Anxiety Disorder and Depression: Contemporary Treatment Approaches","volume":"38","author":"Goodwin","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41392-024-01738-y","article-title":"Major depressive disorder: Hypothesis, mechanism, prevention and treatment","volume":"9","author":"Cui","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"140","DOI":"10.5455\/msm.2023.35.140-145","article-title":"Disability Weights and Years Lived with Disability of Depression with and Without Suicidality","volume":"35","author":"Pranjic","year":"2023","journal-title":"Mater Sociomed"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kim, C.B., Ock, M., Jung, Y.S., Kim, K.B., Kim, Y.E., Kim, K.A., and Yoon, S.J. (2021). Estimation of Years Lived with Disability Using a Prevalence-Based Approach: Application to Major Psychiatric Disease in Korea. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18179056"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/09638237.2020.1765999","article-title":"A comparison of disease burden and the government budget for mental health in Korea","volume":"31","author":"Go","year":"2020","journal-title":"Ment. Health"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sic, A., Bogicevic, M., Brezic, N., Nemr, C., and Knezevic, N.N. (2025). Chronic Stress and Headaches: The Role of the HPA Axis and Autonomic Nervous System. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020463"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"DeMorrow, S. (2018). Role of the Hypothalamic-Pituitary-Adrenal Axis in Health and Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040986"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Surdu, A., Foia, L.G., Luchian, I., Trifan, D., Tatarciuc, M.S., Scutariu, M.M., Ciupilan, C., and Budala, D.G. (2025). Saliva as a Diagnostic Tool for Systemic Diseases\u2014A Narrative Review. Medicina, 61.","DOI":"10.3390\/medicina61020243"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1002\/jssc.202100384","article-title":"Saliva, a bodily fluid with recognized and potential diagnostic applications","volume":"44","author":"Boroumand","year":"2021","journal-title":"Sep. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chojnowska, S., Ptaszy\u0144ska-Sarosiek, I., K\u0119pka, A., Kna\u015b, M., and Waszkiewicz, N. (2021). Salivary Biomarkers of Stress, Anxiety and Depression. Clin. Med., 10.","DOI":"10.3390\/jcm10030517"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tammayan, M., Jantaratnotai, N., and Pachimsawat, P. (2021). Differential responses of salivary cortisol, amylase, and chromogranin A to academic stress. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256172"},{"key":"ref_12","first-page":"247","article-title":"Effect of stress, anxiety and depression on unstimulated salivary flow rate and xerostomia","volume":"11","author":"Gholami","year":"2017","journal-title":"Dent. Res. Dent. Clin. Dent. Prospect."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/ijos.2016.38","article-title":"Saliva in the diagnosis of diseases","volume":"8","author":"Zhang","year":"2016","journal-title":"Int. Oral Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.11613\/BM.2015.018","article-title":"Clinical and diagnostic utility of saliva as a non-invasive diagnostic fluid: A systematic review","volume":"25","author":"Nunes","year":"2015","journal-title":"Biochem. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3390\/psychiatryint5020010","article-title":"Effects of a One-Day Experiential Sheep-Rearing Experience on Motivation, Anxiety, and Frontal Lobe Brain Activity in Patients with Chronic Psychiatric Disorders: A Crossover Pilot Study","volume":"5","author":"Shimizu","year":"2024","journal-title":"Psychiatry Int."},{"key":"ref_16","first-page":"230","article-title":"Stress: Facts and theories through literature review","volume":"2","author":"Shahsavarani","year":"2015","journal-title":"Int. Med Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1177\/0098628316662768","article-title":"Life stress and health","volume":"43","author":"Slavich","year":"2016","journal-title":"Teach. Psychol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Vlenterie, R., Geuijen, P.M., van Gelder, M.M.H.J., and Roeleveld, N. (2021). Questionnaires and salivary cortisol to measure stress and depression in mid-pregnancy. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250459"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sacchini, S., Bombardi, C., Arbelo, M., and Herr\u00e1ez, P. (2023). The Hypothalamus of the Beaked Whales: The Paraventricular, Supraoptic, and Suprachiasmatic Nuclei. Biology, 12.","DOI":"10.3390\/biology12101319"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kageyama, K., Iwasaki, Y., and Daimon, M. (2021). Hypothalamic Regulation of Corticotropin-Releasing Factor under Stress and Stress Resilience. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212242"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.coemr.2021.03.011","article-title":"Sleep and Circadian Regulation of Cortisol: A Short Review","volume":"18","author":"Yuen","year":"2021","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Andreadi, A., Andreadi, S., Todaro, F., Ippoliti, L., Bellia, A., Magrini, A., Chrousos, G.P., and Lauro, D. (2025). Modified Cortisol Circadian Rhythm: The Hidden Toll of Night-Shift Work. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052090"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rusch, J.A., Layden, B.T., and Dugas, L.R. (2023). Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1130689"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nandam, L.S., Brazel, M., Zhou, M., and Jhaveri, D.J. (2020). Cortisol and Major Depressive Disorder-Translating Findings From Humans to Animal Models and Back. Front. Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00974"},{"key":"ref_25","first-page":"673","article-title":"Audiovisual video eyeglass distraction during dental treatment in children","volume":"41","author":"Ram","year":"2010","journal-title":"Quintessence Int."},{"key":"ref_26","first-page":"604","article-title":"Diagnosis and treatment of molar incisor hypomineralization","volume":"27","author":"Wright","year":"2006","journal-title":"Contemp. Dent. Pract."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.psyneuen.2017.05.018","article-title":"Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis","volume":"83","author":"Adam","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.2147\/NDT.S199746","article-title":"Cognitive impairment in depression: Recent advances and novel treatments","volume":"15","author":"Perini","year":"2019","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"James, K.A., Stromin, J.I., Steenkamp, N., and Combrinck, M.I. (2023). Understanding the relationships between physiological and psychosocial stress, cortisol and cognition. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1085950"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1177\/1359105317738323","article-title":"The cortisol awakening response after sleep deprivation: Is the cortisol awakening response a \u201cresponse\u201d to awakening or a circadian process?","volume":"25","author":"Vargas","year":"2020","journal-title":"Health Psychol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.2147\/NDT.S62289","article-title":"The cortisol awakening response and major depression: Examining the evidence","volume":"11","author":"Dedovic","year":"2015","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.psyneuen.2015.09.016","article-title":"Determinants of cortisol awakening responses to naps and nighttime sleep","volume":"63","author":"Devine","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.psyneuen.2015.10.010","article-title":"Assessment of the cortisol awakening response: Expert consensus guidelines","volume":"63","author":"Stalder","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/clinchem\/hvab076","article-title":"Improving the Dexamethasone Suppression Test","volume":"67","author":"Keevil","year":"2021","journal-title":"Clin. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1469-7610.1988.tb00719.x","article-title":"Salivary cortisol hypersecretion in juvenile depression","volume":"29","author":"Foreman","year":"1988","journal-title":"Child Psychol. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/01.psy.0000156939.89050.28","article-title":"Depressive symptoms are associated with blunted cortisol stress responses in very low-income women","volume":"67","author":"Burke","year":"2005","journal-title":"Psychosom. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Qiu, Q., Yang, L., He, M., Gao, W., Mar, H., Li, J., and Wang, G. (2023). The Effects of Forest Therapy on the Blood Pressure and Salivary Cortisol Levels of Urban Residents: A Meta-Analysis. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20010458"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105950","DOI":"10.1016\/j.psyneuen.2022.105950","article-title":"Reliability of three versus five saliva sampling times for assessing the cortisol awakening response","volume":"147","author":"Nasser","year":"2023","journal-title":"Psychoneuroendocrinology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Constantin, V., Luchian, I., Goriuc, A., Budala, D.G., Bida, F.C., Cojocaru, C., Butnaru, O.M., and Virvescu, D.I. (2025). Salivary Biomarkers Identification: Advances in Standard and Emerging Technologies. Oral, 5.","DOI":"10.3390\/oral5020026"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Salahuddin, M.F., Bugingo, R., Mahdi, F., Spencer, D., Manzar, M.D., and Paris, J.J. (2025). Physiological and Psychological Impacts of Shift Work Among Student Pharmacists: Sex Differences in Stress and Health Outcomes. Psychiatry Int., 6.","DOI":"10.3390\/psychiatryint6020047"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Godoy, L.D., Rossignoli, M.T., Delfino-Pereira, P., Garcia-Cairasco, N., and de Lima Umeoka, E.H. (2018). A Comprehensive Overview on Stress Neurobiology: Basic Concepts and Clinical Implications. Front. Behav. Neurosci., 12.","DOI":"10.3389\/fnbeh.2018.00127"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1083\/jcb.200604167","article-title":"Organization of beta-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes","volume":"176","author":"Shcherbakova","year":"2007","journal-title":"Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2147\/NDT.S2380","article-title":"Adenylyl cyclase-cyclicAMP signaling in mood disorders: Role of the crucial phosphorylating enzyme protein kinase A","volume":"4","author":"Dwivedi","year":"2008","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11487","DOI":"10.1074\/jbc.M007631200","article-title":"cAMP-dependent protein kinase induces cAMP-response element-binding protein phosphorylation via an intracellular calcium release\/ERK-dependent pathway in striatal neurons","volume":"276","author":"Zanassi","year":"2001","journal-title":"Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s12529-019-09843-x","article-title":"Salivary Alpha-Amylase as a Biomarker of Stress in Behavioral Medicine","volume":"27","author":"Ali","year":"2020","journal-title":"Int. Behav. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e132","DOI":"10.4317\/jced.51355","article-title":"Usefulness of salivary alpha amylase as a biomarker of chronic stress and stress related oral mucosal changes\u2014A pilot study","volume":"6","author":"Vineetha","year":"2014","journal-title":"Clin. Exp. Dent."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Vors, O., Marqueste, T., and Mascret, N. (2018). The Trier Social Stress Test and the Trier Social Stress Test for groups: Qualitative investigations. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195722"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Guti\u00e9rrez, M.S., Navarrete, F., Sala, F., Gasparyan, A., Austrich-Olivares, A., and Manzanares, J. (2020). Biomarkers in Psychiatry: Concept, Definition, Types and Relevance to the Clinical Reality. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.00432"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Christidis, N., Baghernejad, P., Deyhim, A., and Jasim, H. (2020). Salivary Alpha-Amylase in Experimentally-Induced Muscle Pain. Diagnostics, 10.","DOI":"10.3390\/diagnostics10090722"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dixit, S., Kumar, A., and Srinivasan, K. (2023). A Current Review of Machine Learning and Deep Learning Models in Oral Cancer Diagnosis: Recent Technologies, Open Challenges, and Future Research Directions. Diagnostics, 13.","DOI":"10.3390\/diagnostics13071353"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.archoralbio.2004.06.007","article-title":"Effect of physiological stress on salivary cortisol and amylase levels in healthy young adults","volume":"49","author":"Takai","year":"2004","journal-title":"Arch. Oral Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3109\/10253890902822664","article-title":"Salivary \u03b1-amylase stability, diurnal profile and lack of response to the cold hand test in young women","volume":"12","author":"Kammerer","year":"2009","journal-title":"Stress"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1469-8986.2009.00957.x","article-title":"Salivary alpha-amylase stress reactivity across different age groups","volume":"47","author":"Strahler","year":"2010","journal-title":"Psychophysiology"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yamaguchi, S., Watanabe, K., Sugimura, N., Shishido, I., Konya, I., Fujita, T., Yoshimitsu, Y., Kato, S., Ito, Y.M., and Yano, R. (2022). Salivary Biomarker Profiles and Chronic Fatigue among Nurses Working Rotation Shifts: An Exploratory Pilot Study. Healthcare, 10.","DOI":"10.3390\/healthcare10081416"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Borr\u00e1s, R., Navarrete, J., Bellosta-Batalla, M., Mart\u00ednez-Brot\u00f3ns, C., and Mart\u00ednez-Rubio, D. (2022). Changes in Salivary Immunoglobulin A, Stress, and Burnout in a Workplace Mindfulness Intervention: A Pilot Study. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19106226"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bbi.2015.08.017","article-title":"Psychological distress and salivary secretory immunity","volume":"52","author":"Engeland","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1136\/oem.59.12.836","article-title":"Self perceived work related stress and the relation with salivary IgA and lysozyme among emergency department nurses","volume":"59","author":"Yang","year":"2002","journal-title":"Occup. Environ. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Koh, D., Ng, V., and Naing, L. (2014). Alpha Amylase as a Salivary Biomarker of Acute Stress of Venepuncture from Periodic Medical Examinations. Front. Public Health, 2.","DOI":"10.3389\/fpubh.2014.00121"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1055\/s-0032-1304638","article-title":"Response of salivary markers of autonomic activity to elite competition","volume":"33","author":"Dia","year":"2012","journal-title":"Int. Sports Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/dev.21590","article-title":"Children\u2019s anxiety symptoms and salivary immunoglobulin A: A mutual regulatory system?","volume":"60","author":"Ma","year":"2018","journal-title":"Dev. Psychobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"104912","DOI":"10.1016\/j.psyneuen.2020.104912","article-title":"Salivary free light chains as a new biomarker to measure psychological stress: The impact of a university exam period on salivary immunoglobulins, cortisol, DHEA and symptoms of infection","volume":"122","author":"Irshad","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1001\/jamapediatrics.2021.2482","article-title":"Global Prevalence of Depressive and Anxiety Symptoms in Children and Adolescents During COVID-19: A Meta-analysis","volume":"175","author":"Racine","year":"2021","journal-title":"JAMA Pediatr."},{"key":"ref_63","first-page":"338","article-title":"Confinamiento y distanciamiento social: Estr\u00e9s, ansiedad, depresi\u00f3n en ni\u00f1os y adolescentes [Confinement and social distancing: Stress, anxiety, depression in children and adolescents]","volume":"60","year":"2022","journal-title":"Rev. Med. Inst. Mex. Seguro Soc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2220\/biomedres.19.401","article-title":"Salivary chromogranin a as an index of psychosomatic stress response","volume":"19","author":"Nakane","year":"1998","journal-title":"Biomed. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1080\/14769670600909594","article-title":"Salivary chromogranin-A as a marker of psychological stress during a cognitive test battery in humans","volume":"9","author":"Kanamura","year":"2006","journal-title":"Stress"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.jclinane.2005.08.001","article-title":"Assessment of psychological tension after premedication by measurement of salivary chromogranin A","volume":"17","author":"Obara","year":"2005","journal-title":"Clin. Anesthesiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1080\/08035250500538940","article-title":"Evaluation of psychosomatic stress in children by measuring salivary chromogranin A","volume":"95","author":"Lee","year":"2006","journal-title":"Acta Paediatr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"108","DOI":"10.4103\/1463-1741.33951","article-title":"Salivary chromogranin A as a measure of stress response to noise","volume":"8","author":"Miyakawa","year":"2006","journal-title":"Noise Health"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/da.22353","article-title":"Updated meta-analysis of classical fear conditioning in the anxiety disorders","volume":"32","author":"Duits","year":"2015","journal-title":"Depress. Anxiety"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2220\/biomedres.29.221","article-title":"The effects of examination stress on salivary cortisol, immunoglobulin A, and chromogranin A in nursing students","volume":"29","author":"Takatsuji","year":"2008","journal-title":"Biomed. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cell.2020.05.054","article-title":"Origin and Function of Stress-Induced IL-6 in Murine Models","volume":"182","author":"Qing","year":"2020","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Robinson, R., Srinivasan, M., Shanmugam, A., Ward, A., Ganapathy, V., Bloom, J., Sharma, A., and Sharma, S. (2020). Interleukin-6 trans-signaling inhibition prevents oxidative stress in a mouse model of early diabetic retinopathy. Redox Biol., 34.","DOI":"10.1016\/j.redox.2020.101574"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"112715","DOI":"10.1016\/j.bbr.2020.112715","article-title":"High IL-6 in military personnel relates to multiple traumatic brain injuries and post-traumatic stress disorder","volume":"392","author":"Rodney","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1080\/10253890.2022.2094704","article-title":"Association of stress-related neural activity and baseline interleukin-6 plasma levels in healthy adults","volume":"25","author":"Voges","year":"2022","journal-title":"Stress"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wagnon, I.M., Jabur, L.J., Niedermayer, G., M\u00fcnch, G., Karl, T., Chesworth, R., and Gyengesi, E. (2023). Chronic interleukin-6 mediated neuroinflammation decreases anxiety, and impaires spatial memory in aged female mice. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1267818"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e2412556","DOI":"10.1002\/advs.202412556","article-title":"Microglia-Derived Interleukin-6 Triggers Astrocyte Apoptosis in the Hippocampus and Mediates Depression-Like Behavior","volume":"12","author":"Shen","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e3757","DOI":"10.1210\/clinem\/dgaa476","article-title":"IL-6 Response to Psychosocial Stress Predicts 12-month Changes in Cardiometabolic Biomarkers in Perimenopausal Women","volume":"105","author":"Zannas","year":"2020","journal-title":"Clin. Endocrinol. Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7561","DOI":"10.1017\/S0033291723001290","article-title":"The causal role of C-reactive protein and interleukin-6 on anxiety and depression symptoms and life satisfaction: Mendelian randomisation analyses in the HUNT study","volume":"53","author":"Bekkevold","year":"2023","journal-title":"Psychol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Jang, D.I., Lee, A.H., Shin, H.Y., Song, H.R., Park, J.H., Kang, T.B., Lee, S.R., and Yang, S.H. (2021). The Role of Tumor Necrosis Factor Alpha (TNF-\u03b1) in Autoimmune Disease and Current TNF-\u03b1 Inhibitors in Therapeutics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052719"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.cgh.2020.07.013","article-title":"Anxiety and Depression Leads to Anti-Tumor Necrosis Factor Discontinuation in Inflammatory Bowel Disease","volume":"19","author":"Dolovich","year":"2021","journal-title":"Clin. Gastroenterol Hepatol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Yao, L., Pan, L., Qian, M., Sun, W., Gu, C., Chen, L., Tang, X., Hu, Y., Xu, L., and Wei, Y. (2020). Tumor Necrosis Factor-\u03b1 Variations in Patients with Major Depressive Disorder Before and After Antidepressant Treatment. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.518837"},{"key":"ref_82","first-page":"1056","article-title":"Relationship between Tumor Necrosis Factor-Alpha and Neuropeptide Y Expression and Neurological Function Score in Epileptic Children","volume":"50","author":"Qiu","year":"2021","journal-title":"Iran. Public Health"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Pondeljak, N., Lugovi\u0107-Mihi\u0107, L., Davidovi\u0107, B.L., Karlovi\u0107, D., Han\u017eek, M., and Neuberg, M. (2025). Serum Levels of IL-6 and TNF-\u03b1, Salivary Morning Cortisol and Intensity of Psychological Stress in Patients with Allergic Contact Hand Dermatitis and Healthy Subjects. Life, 15.","DOI":"10.3390\/life15030351"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1177\/0022034519837240","article-title":"Targeted TNF-\u03b1 Overexpression Drives Salivary Gland Inflammation","volume":"98","author":"Limaye","year":"2019","journal-title":"Dent. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bbi.2014.08.008","article-title":"Salivary markers of inflammation in response to acute stress","volume":"44","author":"Slavish","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kibune, R., Muraoka, K., Morishita, M., Ariyoshi, W., and Awano, S. (2022). Relationship between Dynamics of TNF-\u03b1 and Its Soluble Receptors in Saliva and Periodontal Health State. Dent. J., 10.","DOI":"10.3390\/dj10020025"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1111\/ejn.15031","article-title":"C-Reactive protein: Marker of risk for post-traumatic stress disorder and its potential for a mechanistic role in trauma response and recovery","volume":"55","author":"Friend","year":"2022","journal-title":"Eur. J. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Shah, K., Kumari, R., and Jain, M. (2024). Unveiling stress markers: A systematic review investigating psychological stress biomarkers. Dev. Psychobiol., 66.","DOI":"10.1002\/dev.22490"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"100410","DOI":"10.1016\/j.bbih.2021.100410","article-title":"The association of anxiety and stress-related disorders with C-reactive protein (CRP) within UK Biobank","volume":"19","author":"Kennedy","year":"2022","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Akhter, N., Wilson, A., Arefanian, H., Thomas, R., Kochumon, S., Al-Rashed, F., Abu-Farha, M., Al-Madhoun, A., Al-Mulla, F., and Ahmad, R. (2023). Endoplasmic Reticulum Stress Promotes the Expression of TNF-\u03b1 in THP-1 Cells by Mechanisms Involving ROS\/CHOP\/HIF-1\u03b1 and MAPK\/NF-\u03baB Pathways. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015186"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.bbi.2018.07.026","article-title":"Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: Preliminary results","volume":"73","author":"Mehta","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Murawska-Cia\u0142owicz, E., Wiatr, M., Cia\u0142owicz, M., Gomes de Assis, G., Borowicz, W., Rocha-Rodrigues, S., Paprocka-Borowicz, M., and Marques, A. (2021). BDNF Impact on Biological Markers of Depression\u2014Role of Physical Exercise and Training. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18147553"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/mp.2017.144","article-title":"BDNF at the synapse: Why location matters","volume":"22","author":"Song","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"de Assis, G.G., and de Almondes, K.M. (2017). Exercise-dependent BDNF as a modulatory factor for the executive processing of individuals in course of cognitive decline. A systematic review. Front. Psychol., 8.","DOI":"10.3389\/fpsyg.2017.00584"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1080\/15622975.2018.1425478","article-title":"Plasma brain-derived neurotrophic factor (pBDNF) and executive dysfunctions in patients with major depressive disorder","volume":"20","author":"Wagner","year":"2019","journal-title":"World Biol. Psychiatry"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/nyas.14458","article-title":"New insights on brain-derived neurotrophic factor epigenetics: From depression to memory extinction","volume":"1484","author":"Poon","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1017\/S1461145709991234","article-title":"Exercise-induced normalization of decreased BDNF serum concentration in elderly women with remitted major depression","volume":"13","author":"Laske","year":"2010","journal-title":"Int. Neuropsychopharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40263-013-0119-1","article-title":"Role of immune-inflammatory and oxidative and nitrosative stress pathways in the etiology of depression: Therapeutic implications","volume":"28","author":"Anderson","year":"2014","journal-title":"CNS Drugs"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3109\/15622975.2010.545187","article-title":"Serum brain-derived neurotrophic factor: Determinants and relationship with depressive symptoms in a community population of middle-aged and elderly people","volume":"13","author":"Bus","year":"2012","journal-title":"World Biol. Psychiatry"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Schmidt, A.T., Hicks, S.D., Bergquist, B.K., Maloney, K.A., Dennis, V.E., and Bammel, A.C. (2024). Preliminary Evidence for Neuronal Dysfunction Following Adverse Childhood Experiences: An Investigation of Salivary MicroRNA Within a High-Risk Youth Sample. Genes, 15.","DOI":"10.3390\/genes15111433"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/jnc.12609","article-title":"MicroRNA-29b modulates Japanese encephalitis virus-induced microglia activation by targeting tumor necrosis factor \u03b1-induced protein 3","volume":"129","author":"Thounaojam","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jpsychires.2017.08.010","article-title":"FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats","volume":"95","author":"Xu","year":"2017","journal-title":"J. Psychiatr. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/s41380-019-0432-2","article-title":"MicroRNA regulation of persistent stress-enhanced memory","volume":"25","author":"Sillivan","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neuroscience.2015.07.045","article-title":"MicroRNAs as biomarkers of resilience or vulnerability to stress","volume":"305","author":"Chen","year":"2015","journal-title":"Neuroscience"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1016\/j.celrep.2016.10.038","article-title":"Amygdalar microRNA-15a is essential for coping with chronic stress","volume":"17","author":"Volk","year":"2016","journal-title":"Cell Rep."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Kozlowski, T., Bargiel, W., Grabarczyk, M., and Skibinska, M. (2023). Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review. Brain Sci., 13.","DOI":"10.3390\/brainsci13091334"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/jnc.14574","article-title":"The S100B story: From biomarker to active factor in neural injury","volume":"148","author":"Michetti","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.psychres.2016.09.029","article-title":"Cognitive dysfunction correlates with elevated serum S100B concentration in drug-free acutely relapsed patients with schizophrenia","volume":"247","author":"Chen","year":"2017","journal-title":"Psychiatry Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Milleit, B., Smesny, S., Rothermundt, M., Preul, C., Schroeter, M.L., Von Eiff, C., Ponath, G., Milleit, C., Sauer, H., and Gaser, C. (2016). Serum S100B protein is specifically related to white matter changes in Schizophrenia. Front. Cell. Neurosci., 10.","DOI":"10.3389\/fncel.2016.00033"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jpsychires.2022.05.004","article-title":"Predictive effect of Bayes discrimination in the level of serum protein factors and cognitive dysfunction in schizophrenia","volume":"151","author":"Huang","year":"2022","journal-title":"Psychiatr. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.cellbio.17.1.463","article-title":"How matrix metalloproteinases regulate cell behavior","volume":"17","author":"Sternlicht","year":"2021","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Costa, D., Scalise, E., Ielapi, N., Bracale, U.M., Andreucci, M., and Serra, R. (2024). Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease. Biomolecules, 14.","DOI":"10.3390\/biom14010096"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1007\/s00018-019-03171-9","article-title":"Matrix metalloproteinases in the CNS: Interferons get nervous","volume":"76","author":"Chopra","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_114","first-page":"282","article-title":"Metalloproteinases between History, Health, Disease, and the Complex Dimension of Social Determinants of Health","volume":"2","author":"Costa","year":"2023","journal-title":"Vasc. Dis."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Luchian, I., Goriuc, A., Sandu, D., and Covasa, M. (2022). The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031806"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/jre.12524","article-title":"The Role of Extracellular Matrix Metalloproteinase Inducer Glycosylation in Regulating Matrix Metalloproteinases in Periodontitis","volume":"53","author":"Zhang","year":"2018","journal-title":"Periodontal Res."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/7\/488\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:58:53Z","timestamp":1760032733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/7\/488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,26]]},"references-count":116,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cimb47070488"],"URL":"https:\/\/doi.org\/10.3390\/cimb47070488","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,26]]}}}