Salivary Biomarkers of Stress, Anxiety and Depression

Sylwia Chojnowska, Iwona Ptaszyńska-Sarosiek, Alina Kępka, Małgorzata Knaś, Napoleon Waszkiewicz, Sylwia Chojnowska, Iwona Ptaszyńska-Sarosiek, Alina Kępka, Małgorzata Knaś, Napoleon Waszkiewicz

Abstract

Stress, anxiety and depressive disorders are often characterized by the activation of the stress axis, which results in similar symptoms at some point in these disorders. These disorders are closely related to each other-they occur simultaneously or follow one another. The diagnosis of stress, anxiety and depression is not a perfect procedure currently-it is based on patient observation and an interview with the patient and their family. There are no laboratory tests that would dispel the doubts of the doctor making the diagnosis and allow the appropriate treatment to be implemented as soon as possible. Therefore, this study will review the components of saliva that could be helpful in the quick diagnosis of stress, anxiety and/or depression. Such potential salivary biomarkers could also be useful in monitoring the effectiveness of pharmacological treatment prescribed by a psychiatrist. The following are promising salivary biomarkers of stress, anxiety or depression: cortisol, immunoglobulin A (sIgA), lysozyme, melatonin, α-amylase (sAA), chromogranin A (CgA) and fibroblast growth factor 2 (FGF-2). To the best valuable potential salivary markers of stress, we can include cortisol, lysozyme, sAA and CgA. To differentiate depression from stress, salivary cortisol and melatonin can be helpful. Fluctuations in the concentrations of the above-mentioned substances in saliva indicate a particularly strong relationship with typical human psychological problems, such as stress, depression or anxiety.

Keywords: anxiety; depression; salivary biomarkers; stress.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The procedure currently used to diagnose stress, anxiety and depression.

References

    1. World Health Organization . The ICD-10 Classiffication of Mental and Behavior Disorders: Clinical Description and Diagnostics Guideline. WHO; Geneva, Switzerland: 1992.
    1. Wang F.S., Aguilar-Gaxiola S., Alonso J., Angermeyer M.C., Borges G., Bromet E.J., Bruffaerts R., De Girolamo G., De Graaf R., Gureje O., et al. Use of mental health services for anxiety, mood, and substance disorders in 17 countries in the WHO world mental health surveys. Lancet. 2007;370:841–850. doi: 10.1016/S0140-6736(07)61414-7.
    1. Nobis A., Zalewski D., Waszkiewicz N. Peripheral Markers of Depression. J. Clin. Med. 2020;9:3793. doi: 10.3390/jcm9123793.
    1. Angold A., Costello E.J. Depressive comorbidity in children andadolescents: Empirical, theoretical, and methodological issues. Am. J. Psychiatr. 1993;150:1779–1791.
    1. Stein D.J., Hollander E. Współchorobowość Depresji i Zaburzeń Lękowych. Via Medica; Gdańsk, Poland: 2004.
    1. Graaf R., Bijl R.V., Spijker J., Beekman A.T.F., Vollebergh W.A.M. Temporal sequencing of lifetime mood disorders in relation to comorbid anxiety and substance use disorders. Findings from the Netherlands Mental Health and Incidence Study. Soc. Psychiatr. Psychiatr. Epidemiol. 2003;38:1–11. doi: 10.1007/s00127-003-0597-4.
    1. Wittchen H.U., Kessler R.C., Pfister H., Lieb M. Why do people with anxiety disorders become depressed? A prospective-longitudinal community study. Acta Psychiatr. Scand. 2000;406:14–23. doi: 10.1111/j.0065-1591.2000.acp29-03.x.
    1. McEwen B.S. Stress, adaptation, and disease. Allostasis and allostatic load. Ann. N. Y. Acad. Sci. 1998;840:33–44. doi: 10.1111/j.1749-6632.1998.tb09546.x.
    1. Middeldorp C., Cath D.C., Van Dyck R., Boomsma D.I. The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychol. Med. 1999;35:611–624. doi: 10.1017/S003329170400412X.
    1. Boyer P. Do anxiety and depression have a common pathophysiological mechanism? Acta Psychiatr. Scand. 2000;406:24–29. doi: 10.1111/j.0065-1591.2000.acp29-04.x.
    1. Chaves C., Castellanos T., Abrams M., Vazquez C. The impact of economic recessions on depression and individual and social well-being: The case of Spain (2006–2013) Soc. Psychiatr. Psychiatr. Epidemiol. 2018;53:977–986. doi: 10.1007/s00127-018-1558-2.
    1. Beaglehole B., Mulder R.T., Frampton C.M., Boden J.M., Newton-Howes G., Bell C.J. Psychological distress and psychiatric disorder after natural disasters: Systematic review and metaanalysis. Br. J. Psychiatr. 2018;213:716–722. doi: 10.1192/bjp.2018.210.
    1. Alonso J., Angermeyer M.C., Bernet S., Bruffaerts T.S., Brugha H., Bryson G., de Girolamo R., Graaf K., Demyttenaere I., Gasquet J.M., et al. Prevalence of mental disorders in Europe: Results from European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr. Scand. 2004;109:21–27. doi: 10.1111/j.1600-0047.2004.00325.x.
    1. McEwen B.S. The neurobiology of stress: From serendipity to clinical relevance. Brain Res. 2000;886:172–189. doi: 10.1016/S0006-8993(00)02950-4.
    1. Maes M., Kubera M., Obuchowiczwa E., Goehler L.E., Brzeszcz J. Depression’s multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways. Neuro Endocrinol. Lett. 2011;32:7–24.
    1. Kendler K.S., Thornton L.M., Gardner C.O. Stressful life events and previous episodes in the etiology of major depression in women: An evaluation of the “kindling” hypothesis. Am. J. Psychiatr. 2000;157:1243–1251. doi: 10.1176/appi.ajp.157.8.1243.
    1. Beck A.T., Ward C.H., Mendelson M., Mock J., Erbaugh J. An Inventory for Measuring Depression. Arch. Gen. Psychiatr. 1961;4:561–571. doi: 10.1001/archpsyc.1961.01710120031004.
    1. Hamilton M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatr. 1960;23:56–62. doi: 10.1136/jnnp.23.1.56.
    1. Montgomery S.A., Åsberg M. A New Depression Scale Designed to be Sensitive to Change. Br. J. Psychiatr. 1979;134:382–389. doi: 10.1192/bjp.134.4.382.
    1. Chojnowska S., Baran T., Wilińska I., Sienicka P., Cabaj-Wiater I., Knaś M. Human saliva as a diagnostic material. Adv. Med. Sci. 2018;63:185–191. doi: 10.1016/j.advms.2017.11.002.
    1. Kaufman E., Lamster I.B. The diagnostic applications of saliva—A review. Crit. Rev. Oral Biol. Med. 2002;13:197–212. doi: 10.1177/154411130201300209.
    1. Nunes L.A., Mussavira S., Bindhu O.S. Clinical and diagnostic utility of saliva as a non-invasive diagnostic fluid: A systematic review. Biochem. Med. 2015;25:177–192. doi: 10.11613/BM.2015.018.
    1. Kochurova E.V., Kozlov S.V. The diagnostic possibilities of saliva. Klin. Lab. Diagn. 2014;1:13–15.
    1. Al Kawas S.A., Rahim Z.H., Ferguson D.B. Potential uses of human salivary protein and peptide analysis in the diagnostic of disease. Arch. Oral Biol. 2012;57:1–9. doi: 10.1016/j.archoralbio.2011.06.013.
    1. Wong D.T. Saliva the body’s mirror. Dimens. Dent. Hyg. 2006;4:14–17.
    1. Ivkovic N., Bozovic A., Racic M., Popovic-Grubac D., Davidovic B. Biomarkers of stress in saliva. Acta Facult. Med. Nis. 2015;32:91–99.
    1. Stachniuk J., Kubalczyk P., Furmaniak P., Głowacki R. A versatile method for analysis of saliva, plasma and urine for total thiols using HPLC with UV detection. Talanta. 2016;155:70–77. doi: 10.1016/j.talanta.2016.04.031.
    1. Hartwig S., Auwärter V., Pragst F. Effect of hair care and hair cosmetics on the concentrations of fatty acid ethyl esters in hair as markers of chronically elevated alcohol consumption. Forensic Sci. Int. 2003;131:90–97. doi: 10.1016/S0379-0738(02)00412-7.
    1. Sternberg E.M. Neural regulation of innate immunity: A coordinated nonspecific host response to pathogens. Nat. Rev. Immunol. 2006;6:318–328. doi: 10.1038/nri1810.
    1. Gozansky W.S., Lynn J.S., Laudenslager M.L., Kohrt W.M. Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic-pituitary-adrenal axis activity. Clin. Endocrinol. 2005;63:336–341. doi: 10.1111/j.1365-2265.2005.02349.x.
    1. Schwartz E.B., Granger D.A., Susman E.J., Gunnar M.R., Laird B. Assessing salivary cortisol in studies of child development. Child Develop. 1998;69:1503–1513. doi: 10.1111/j.1467-8624.1998.tb06173.x.
    1. Johnson L.R., editor. Essential Medical Physiology. 3rd ed. Elsevier Academic Press; San Diego, CA, USA: 2003. pp. 499–502.
    1. Hellhammer D.H., Wüst S., Kudielka B.M. Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology. 2009;34:163–171. doi: 10.1016/j.psyneuen.2008.10.026.
    1. Schoofs D., Hartmann R., Wolf O.T. Neuroendocrine stress responses to an oral academic examination: No strong influence of sex, repeated participation and personality traits. Stress. 2008;11:52–61. doi: 10.1080/10253890701453943.
    1. Gröschl M. Current Status of Salivary Hormone Analysis. Clin. Chem. 2008;54:1759–1769. doi: 10.1373/clinchem.2008.108910.
    1. Clow A., Hucklebridge F., Thorn L. The Cortisol Awakening Response in Context. Int. Rev. Neurobiol. 2010;93:153–175. doi: 10.1016/s0074-7742(10)93007-9.
    1. Miller G.E., Chen E., Zhou E.S. If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychol. Bull. 2007;133:25–45. doi: 10.1037/0033-2909.133.1.25.
    1. Heim C., Ehlert U., Hellhammer D.H. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000;25:1–35. doi: 10.1016/S0306-4530(99)00035-9.
    1. Fries E., Hesse J., Hellhammer J., Hellhammer D.H. A new view on hypocortisolism. Psychoneuroendocrinology. 2005;30:1010–1016. doi: 10.1016/j.psyneuen.2005.04.006.
    1. Hek K., Direk N., Newson R.S., Hofman A., Hoogendijk W.J.G., Mulder C.L., Tiemeier H. Anxiety disorders and salivary cortisol levels in older adults: A population-based study. Psychoneuroendocrinology. 2013;38:300–305. doi: 10.1016/j.psyneuen.2012.06.006.
    1. Yonekura T., Takeda K., Shetty V., Yamaguchi M. Relationship between salivary cortisol and depression in adolescent survivors of a major natural disaster. J. Physiol. Sci. 2014;64:261–267. doi: 10.1007/s12576-014-0315-x.
    1. Knorr U., Vinberg M., Kessing L.V., Wetterslev J. Salivary cortisol in depressed patients versus control persons: A systematic review and meta-analysis. Psychoneuroendocrinology. 2010;35:1275–1286. doi: 10.1016/j.psyneuen.2010.04.001.
    1. Cohen S., Miller G.E., Rabin B.S. Psychological stress and antibody response to immunization: A critical review of the human literature. Psychosom. Med. 2001;63:7–18. doi: 10.1097/00006842-200101000-00002.
    1. Nomura S., Handri S., Honda H. Development of a bionanodevice for detecting stress levels. IOP Conf. Ser. Mater. Sci. Eng. 2011;21:012029. doi: 10.1088/1757-899X/21/1/012029.
    1. Svobodová I., Chaloupková H., Koncel R., Bartos L., Hradecká L., Jebavý L. Cortisol and Secretory Immunoglobulin A Response to Stress in German Shepherd Dogs. PLoS ONE. 2014;9:e90820. doi: 10.1371/journal.pone.0090820.
    1. Engeland C.G., Hugo F.N., Hilgert J.B., Nascimento G.G., Celeste R.K., Lim H.-J., Marucha P.T., Bosch J.A. Psychological distress and salivary secretory immunity. Brain Behav. Immun. 2016;52:11–17. doi: 10.1016/j.bbi.2015.08.017.
    1. Sava G., Benetti A., Ceschia V., Pacor S. Lysozyme and cancer: Role of exogenous lysozyme as anticancer agent (review) Anticancer. Res. 1989;9:583–591.
    1. Lee-Huang S., Huang P.L., Sun Y., Huang P.L., Kung S., Blithe D.L., Hen H. Lysozyme and RNases as anti-HIV compo-nents in β-core preparations of human chorionic gonadotropin. Proc. Natl. Acad. Sci. USA. 1999;96:2678–2681. doi: 10.1073/pnas.96.6.2678.
    1. Perera S., Uddin M., Hayes J.A. Salivary lysozyme: A noninvasive marker for the study of the effects of stress on natural immunity. Int. J. Behav. Med. 1997;4:170–178. doi: 10.1207/s15327558ijbm0402_5.
    1. Yang Y., Koh D., Ng V., Lee C.Y., Chan G., Dong F., Goh S.H., Anantharaman V., Chia S.E. Self perceived work related stress and the relation with salivary IgA and lysozyme among emergency department nurses. Occup. Environ. Med. 2002;59:836–841. doi: 10.1136/oem.59.12.836.
    1. Allgrove J.E., Oliveira M., Gleeson M. Stimulating whole saliva affects the response of antimicrobial proteins to exercise. Scand. J. Med. Sci. Sports. 2013;24:649–655. doi: 10.1111/sms.12056.
    1. Abey S.K., Yuana Y., Joseph P.V., Kenea N.D., Fourie N.H., Sherwin L.B., Gonye G.E., Smyser P.A., Stempinski E.S., Boulineaux C.M., et al. Lysozyme association with circulating RNA, extracellular vesicles, and chronic stress. BBA Clin. 2017;7:23–35. doi: 10.1016/j.bbacli.2016.12.003.
    1. Dubocovich M.L., Yun K., Al-Ghoul W.M., Benloucif S., Monica I., Masana M.I. Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J. 1998;12:1211–1220. doi: 10.1096/fasebj.12.12.1211.
    1. Karasek M. Clinical significance of melatonin. Post N. Med. 2007;10:395–398.
    1. Tsuno N., Besset A., Ritchie K. Sleep and Depression. J. Clin. Psychiatr. 2005;66:1254–1269. doi: 10.4088/JCP.v66n1008.
    1. Heitzman J. Zaburzenia snu—Przyczyna czy skutek depresji? Psych. Pol. 2009;43:499–511.
    1. Voultsios A., Kennaway D.J., Dawson D. Salivary Melatonin as a Circadian Phase Marker: Validation and Comparison to Plasma Melatonin. J. Biol. Rhythm. 1997;12:457–466. doi: 10.1177/074873049701200507.
    1. Ito Y., Iida T., Yamamura Y., Teramura M., Nakagami Y., Kawai K., Nagamura Y., Teradaira R. Relationships between Salivary Melatonin Levels, Quality of Sleep, and Stress in Young Japanese Females. Int. J. Tryptophan Res. 2013;6:75–85. doi: 10.4137/IJTR.S11760.
    1. Paul M.A., Love R.J., Jetly R., Richardson J.D., Lanius R.A., Miller J.C., Macdonald M., Rhind S.G. Blunted Nocturnal Salivary Melatonin Secretion Profiles in Military-Related Posttraumatic Stress Disorder. Front. Psychiatr. 2019;10:882. doi: 10.3389/fpsyt.2019.00882.
    1. Sundberg I., Ramklint M., Stridsberg M., Papadopoulos F.C., Ekselius L., Cunningham J.L. Salivary Melatonin in Relation to Depressive Symptom Severity in Young Adults. PLoS ONE. 2016;11:e0152814. doi: 10.1371/journal.pone.0152814.
    1. Scannapieco F.A., Torres G., Levine M.J. Salivary α-Amylase: Role in Dental Plaque and Caries Formation. Crit. Rev. Oral Biol. Med. 1993;4:301–307. doi: 10.1177/10454411930040030701.
    1. Takai N., Yamaguchi M., Aragaki T., Eto K., Uchihashi K., Nishikawa Y. Effect of physiological stress on salivary cortisol and amylase levels in healthy young adults. Arch. Oral Biol. 2004;49:963–968. doi: 10.1016/j.archoralbio.2004.06.007.
    1. O’Donnell K., Kammerer M., O’Reilly R., Taylor A., Glover V. Salivary α-amylase stability, diurnal profile and lack of response to the cold hand test in young women. Stress. 2009;12:549–554. doi: 10.3109/10253890902822664.
    1. Strahler J., Mueller A., Rosenloecher F., Kirschbaum C., Rohleder N. Salivary alpha-amylase stress reactivity across different age groups. Psychophysiology. 2010;47:587–595. doi: 10.1111/j.1469-8986.2009.00957.x.
    1. Koh D., Ng V., Naing L. Alpha Amylase as a Salivary Biomarker of Acute Stress of Venepuncture from Periodic Medical Examinations. Front. Public Health. 2014;2:121. doi: 10.3389/fpubh.2014.00121.
    1. Jafari A., Pouramir M., Shirzad A., Motallebnejad M., Bijani A., Moudi S., Abolghasem-Zade F., Dastan Z. Evaluation of Salivary Alpha Amylase as a Biomarker for Dental Anxiety. Iran. J. Psychiatr. Behav. Sci. 2018;12:9350. doi: 10.5812/ijpbs.9350.
    1. Vineetha R., Pai K.M., Vengal M., Gopalakrishna K., Narayanakurup D. Usefulness of salivary alpha amylase as a biomarker of chronic stress and stress related oral mucosal changes—A pilot study. J. Clin. Exp. Dent. 2014;6:e132–e137. doi: 10.4317/jced.51355.
    1. Van Veen J., Van Vliet I., De Rijk R., Van Pelt J., Mertens B., Zitman F. Elevated alpha-amylase but not cortisol in generalized social anxiety disorder. Psychoneuroendocrinology. 2008;33:1313–1321. doi: 10.1016/j.psyneuen.2008.07.004.
    1. Nagasawa S., Nishikawa Y., Li J., Futai Y. Simple enzyme immunoassay for the measurement of immunoreactive chromogranin A in human plasma, urine and saliva. Biomed. Res. 1998;19:407–410. doi: 10.2220/biomedres.19.407.
    1. Nishikawa Y., Li J., Futai Y., Yanaihara N., Iguchi K., Mochizuki T., Hoshino M., Janaichara C. Region-specific radio-immunoassay for human chromogranin A. Biomed. Res. 1998;19:245–251. doi: 10.2220/biomedres.19.245.
    1. Escribano D., Gutierrez A.M., Tecles F., Ceron J.J. Changes in saliva biomarkers of stress and immunity in domestic pigs exposed to a psychosocial stressor. Res. Vet. Sci. 2015;102:38–44. doi: 10.1016/j.rvsc.2015.07.013.
    1. Nakane H., Asami O., Yamada Y., Harada T., Matsui N., Kanno T., Yanaihara N. Salivary chromogranin a as an index of psychosomatic stress response. Biomed. Res. 1998;19:401–406. doi: 10.2220/biomedres.19.401.
    1. Nakane H., Asami O., Yamada Y., Harada T., Matsui N., Kanno T., Yanaihara N. Effect of negative air ions on computer operation, anxiety and salivary chromogranin A-like immunoreactivity. Int. J. Psychophysiol. 2002;46:85–89. doi: 10.1016/S0167-8760(02)00067-3.
    1. Kanamura Y., Kikukawa A., Shimamura K. Salivary chromogranin-A as a marker of psychological stress during a cognitive test battery in humans. Stress. 2006;9:127–131. doi: 10.1080/14769670600909594.
    1. Ng V., Koh D., Mok B.Y., Chia S.E., Lim L.P. Salivary biomarkers associated with academic assessment stress among dental undergraduates. J. Dent. Educ. 2003;67:1091–1094. doi: 10.1002/j.0022-0337.2003.67.10.tb03701.x.
    1. Obara S., Iwama H. Assessment of psychological tension after premedication by measurement of salivary chromogranin A. J. Clin. Anesthesiol. 2005;17:554–557. doi: 10.1016/j.jclinane.2005.08.001.
    1. Hua J., Le S.C., Larue J., Joséf M.J.C., Devillers L., Filaire E. Global stress response during asocial stress test: Impact of alexithymia and its subfactors. Psychoneuroendocrinol. 2014;50:53–61. doi: 10.1016/j.psyneuen.2014.08.003.
    1. Dia M.M., Bocanegra O.L., Teixeira R.R., Soares S.S., Espindola F.S. Response of salivary markers of autonomicactivity to elite competition. Int. J. Sports Med. 2012;33:763–768.
    1. Lee T., Shimizu T., Iijima M., Obinata K., Yamashiro Y., Nagasawa S. Evaluation of psychosomatic stress in children by measuring salivary chromogranin A. Acta Paediatr. 2006;95:935–939. doi: 10.1080/08035250500538940.
    1. Miyakawa M., Matsui T., Kishikawa H., Murayama R., Uchiyama I., Itoh T., Yoshida T. Salivary chromogranin A as a measure of stress response to noise. Noise Health. 2006;8:108. doi: 10.4103/1463-1741.33951.
    1. Takatsuji K., Sugimoto Y., Ishizaki S., Ozaki Y., Matsuyama E., Yamaguchi Y. The effects of examination stresson salivary cortisol, immunoglobulin A, and chromogranin A in nursing students. Biomed. Res. 2008;29:221–224. doi: 10.2220/biomedres.29.221.
    1. Muneta Y., Yoshikawa T., Minagawa Y., Shibahara T., Maeda R., Omata Y. Salivary IgA as a useful non-invasive marker for restraint stress in pigs. J. Vet. Med. Sci. 2010;72:1295–1300. doi: 10.1292/jvms.10-0009.
    1. Graham B.M., Richardson R. Memory of fearful events: The role of fibroblast growth factor-2 in fear acquisition and extinction. Neuroscience. 2011;189:156–169. doi: 10.1016/j.neuroscience.2011.05.041.
    1. Graham B.M., Richardson R. Fibroblast growth factor-2 as a new approach to fighting fear. JAMA Psychiatr. 2015;72:959–960. doi: 10.1001/jamapsychiatry.2015.1187.
    1. Graham B.M. Fibroblast Growth Factor-2: A Promising Biomarker for Anxiety and Trauma Disorders. J. Exp. Neurosci. 2017;11:117906951774958. doi: 10.1177/1179069517749589.
    1. Duits P., Cath D.C., Lissek S., Hox J.J., Hamm A.O., Engelhard I.M., Van Den Hout M.A., Baas J.M.P. Updated meta-analysis of classical fear conditioning in the anxiety disorders. Depress. Anxiety. 2015;32:239–253. doi: 10.1002/da.22353.
    1. Bland S.T., Schmid M.J., Greenwood B.N., Watkins L.R., Maier S.F. Behavioral control of the stressor modulates stress-induced changes in neurogenesis and fibroblast growth factor-2. NeuroReport. 2006;17:593–597. doi: 10.1097/00001756-200604240-00008.
    1. Bland S.T., Tamlyn J.P., Barrientos R.M., Greenwood B.N., Watkins L.R., Campeau S., Day H.E., Maier S.F. Expression of fibroblast growth factor-2 and brain-derived neurotrophic factor mRNA in the medial prefrontal cortex and hippocampus after uncontrollable or controllable stress. Neuroscience. 2007;144:1219–1228. doi: 10.1016/j.neuroscience.2006.11.026.
    1. Giltaya E.J., Enter D., Zitmana F.G., Penninx B.W.J.H., Van Pelte J., Spinhoven J., Roelofs K. Salivary testosterone: Associations with depression, anxiety disorders, and antidepressant use in a large cohort study. J. Psychosom. Res. 2012;72:205–213. doi: 10.1016/j.jpsychores.2011.11.014.
    1. Kułak-Bejda A., Waszkiewicz N., Bejda G., Zalewska A., Maciejczyk M. Diagnostic Value of Salivary Markers in Neuropsychiatric Disorders. Dis. Markers. 2019;2019:4360612. doi: 10.1155/2019/4360612.
    1. Henry J., Carrier N., Hull N., Kabbaj M. Sex diferences in anxiety and depression: Role of testosterone. Front. Neuroendocrinol. 2014;35:42–57.
    1. Islam R., Islam R., Ahmed I., Moktadir A.A., Nahar Z., Islam M.S., Shahid S.F.B., Islam S.N., Islam S., Hasnat A. Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: A case-control study. SAGE Open Med. 2018;6:2050312118773953. doi: 10.1177/2050312118773953.
    1. Xu Y.Y., Ge J.F., Liang J., Cao Y., Shan F., Liu Y., Yan C.-Y., Xia Q.-R. Nesfatin-1 and cortisol: Potential novel diagnostic biomarkers in moderate and severe depressive disorder. Psychol. Res. Behav. Manag. 2018;11:495–502. doi: 10.2147/PRBM.S183126.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren