Investigation of Neopterin and Neurophysiological Measurements as Biomarkers of Anxiety and Stress
DOI:
https://doi.org/10.15540/nr.11.1.25Keywords:
anxiety, biomarkers, brainwaves, heart rate variability, inflammation, neopterin, stressAbstract
The aim of this study was to investigate whether the inflammatory marker neopterin and certain neurophysiological measurements could be used as complementary markers for stress and anxiety symptoms as determined by the Depression, Anxiety, and Stress Scale (DASS-21) questionnaire. A cohort of 158 respondents completed the DASS-21 and biographical questionnaire which were used to stratify health sciences university students between Group A (n = 20), who had high levels of symptoms, and Group B (n = 20) who had normal levels of stress and anxiety. Neurophysiological measurements were taken from these participants, namely heart rate variability (HRV), blood pressure (BP), blood-volume pulse (BVP), electrodermal activity (EDA), and quantitative electroencephalography (qEEG). Each participant also donated a urine sample which was tested for neopterin concentration using an enzyme-linked immunosorbent assay (ELISA). Neopterin positively correlated with the stress and anxiety scores, while HRV and BVP were negatively correlated with these scores. In terms of qEEG, delta and hibeta wave activity increased in the left and frontal brain regions of participants with high mental health scores, whereas alpha wave activity decreased in these regions. High DASS scores were associated with elevated neopterin concentration and neurophysiological changes (brain waves, HRV, and BVP).
References
Akin, A., & Çetin, B. (2007). The Depression Anxiety and Stress Scale (DASS): The study of validity and reliability. Kuram ve Uygulamada Egitim Bilimleri, 7(1), 260–268.
Albert, P. R., Benkelfat, C., & Descarries, L. (2012). The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philosophical Transactions of the Royal Society B: Biological Sciences, 367(1601), 2378–2381. https://doi.org/10.1098/rstb.2012.0190
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
An, E., Nolty, A. A. T., Amano, S. S., Rizzo, A. A., Buckwalter, J. G., & Rensberger, J. (2020). Heart rate variability as an index of resilience. Military Medicine, 185(3–4), 363–369. https://doi.org/10.1093/milmed/usz325
Antony, M., Bieling, P., Cox, B., Enns, M., & Swinson, R. (1998). Psychometric properties of the 42-item and 21-item versions of the Depression Anxiety Stress Scales in clinical groups and a community sample. Psychological Assessment, 10(2), 176–181. https://doi.org/10.1037/1040-3590.10.2.176
Arias, D., Saxena, S., & Verguet, S. (2022). Quantifying the global burden of mental disorders and their economic value. eClinicalMedicine, 54, Article 101675. https://doi.org/10.1016/j.eclinm.2022.101675
Atmaca, M., Kuloglu, M., Tezcan, E., Onal, S. l., & Ustundag, B. (2002). Neopterin levels and dexamethasone suppression test in posttraumatic stress disorder. European Archives of Psychiatry and Clinical Neuroscience, 252(4), 161–165. https://doi.org/10.1007/s00406-002-0374-5
Awadalla, S., Davies, E. B., & Glazebrook, C. (2020). A longitudinal cohort study to explore the relationship between depression, anxiety and academic performance among Emirati university students. BMC Psychiatry, 20(1), Article 448. https://doi.org/10.1186/s12888-020-02854-z
Bagdy, G. (1998). Serotonin, anxiety, and stress hormones: Focus on 5-HT receptor subtypes, species and gender differencesa. Annals of the New York Academy of Sciences, 851(1), 357–363. https://doi.org/10.1111/j.1749-6632.1998.tb09009.x
Bankier, B., Barajas, J., Martinez-Rumayor, A., & Januzzi, J. L. (2008). Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients. European Heart Journal, 29(18), 2212–2217. https://doi.org/10.1093/eurheartj/ehn326
Bauer, M. E., & Teixeira, A. L. (2019). Inflammation in psychiatric disorders: What comes first? Annals of the New York Academy of Sciences, 1437(1), 57–67. https://doi.org/10.1111/nyas.13712
Beaufort, I. N., De Weert-Van Oene, G. H., Buwalda, V. A. J., de Leeuw, J. R. J., & Goudriaan, A. E. (2017). The Depression, Anxiety and Stress Scale (DASS-21) as a screener for depression in substance use disorder inpatients: A pilot study. European Addiction Research, 23(5), 260–268. https://doi.org/10.1159/000485182
Berdowska, A., & Zwirska-Korczala, K. (2001). Neopterin measurement in clinical diagnosis. Journal of Clinical Pharmacy and Therapeutics, 26(5), 319–329. https://doi.org/10.1046/j.1365-2710.2001.00358.x
Blackhart, G. C., Minnix, J. A., & Kline, J. P. (2006). Can EEG asymmetry patterns predict future development of anxiety and depression?: A preliminary study. Biological Psychology, 72(1), 46–50. https://doi.org/10.1016/j.biopsycho.2005.06.010
Blokland, A., Lieben, C., & Deutz, N. E. P. (2002). Anxiogenic and depressive-like effects, but no cognitive deficits, after repeated moderate tryptophan depletion in the rat. Journal of Psychopharmacology, 16(1), 39–49. https://doi.org/10.1177/026988110201600112
Bouayed, J., Rammal, H., & Soulimani, R. (2009). Oxidative stress and anxiety: Relationship and cellular pathways. Oxidative Medicine and Cellular Longevity, 2(2), 63–67. https://doi.org/10.4161/oxim.2.2.7944
Brown, R. R., Lee, C. M., Kohler, P. C., Hank, J. A., Storer, B. E., & Sondel, P. M. (1989). Altered tryptophan and neopterin metabolism in cancer patients treated with recombinant interleukin 21. Cancer Research, 49(17), 4941–4944.
Buist–Bouwman, M. A., De Graaf, R., Vollebergh, W. A. M., Alonso, J., Bruffaerts, R., Ormel, J., & ESEMeD/MHEDEA 2000 Investigators (2006). Functional disability of mental disorders and comparison with physical disorders: A study among the general population of six European countries. Acta Psychiatrica Scandinavica, 113(6), 492–500. https://doi.org/10.1111/j.1600-0447.2005.00684.x
Capuron, L., & Castanon, N. (2016). Role of inflammation in the development of neuropsychiatric symptom domains: Evidence and mechanisms. In R. Dantzer & L. Capuron (Eds.), Inflammation-associated depression: Evidence, mechanisms and implications (pp. 31–44). Current topics in behavioral neurosciences (vol. 31). Springer, Cham. https://doi.org/10.1007/7854_2016_14
Chalmers, J. A., Quintana, D. S., Abbott, M. J., & Kemp, A. H. (2014). Anxiety disorders are associated with reduced heart rate variability: A meta-analysis. Frontiers in Psychiatry, 5, Article 80. https://doi.org/10.3389/fpsyt.2014.00080
Charmandari, E., Tsigos, C., & Chrousos, G. (2005). Endocrinology of the stress response. Annual Review of Physiology, 67, 259–284. https://doi.org/10.1146/annurev.physiol.67.040403.120816
Chu, B., Marwaha, K., Sanvictores, T., & Ayers, D. (2022). Physiology, stress reaction. StatPearls. StatPearls Publishing.
Cohen, B. E., Edmondson, D., & Kronish, I. M. (2015). State of the art review: Depression, stress, anxiety, and cardiovascular disease. American Journal of Hypertension, 28(11), 1295–1302. https://doi.org/10.1093/ajh/hpv047
Crawford, J. R., & Henry, J. D. (2003). The Depression Anxiety Stress Scales (DASS): Normative data and latent structure in a large non-clinical sample. British Journal of Clinical Psychology, 42(2), 111–131. https://doi.org/10.1348/014466503321903544
Crestani, F., Lorez, M., Baer, K., Essrich, C., Benke, D., Laurent, J. P., Belzung, C., Fritschy, J. M., Lüscher, B., & Mohler, H. (1999). Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Nature Neuroscience, 2(9), 833–839. https://doi.org/10.1038/12207
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience, 9(1), 46–56. https://doi.org/10.1038/nrn2297
De Beurs, E., Van Dyck, R., Marquenie, Lange, A., & Blonk, R. (2001). De DASS: Een vragenlijst voor het meten van epressivee, angst en stress [The DASS: A questionnaire for the measurement of depression, anxiety, and stress]. Gedragstherapie, 34(1), 35–53.
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67(5), 446–457. https://doi.org/10.1016/j.biopsych.2009.09.033
Dreyer, Z., Henn, C., & Hill, C. (2019). Validation of the Depression Anxiety Stress Scale-21 (DASS-21) in a non-clinical sample of South African working adults. Journal of Psychology in Africa, 29(4), 346–353. https://doi.org/10.1080/14330237.2019.1647499
Dunbar, P. R., Hill, J., & Neale, T. J. (1993). Urinary neopterin quantification indicates altered cell-mediated immunity in healthy subjects under psychological stress. Australian & New Zealand Journal of Psychiatry, 27(3), 495–501. https://doi.org/10.3109/00048679309075808
Dunbar, P. R., Hill, J., Neale, T. J., & Mellsop, G. W. (1992). Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. Psychological Medicine, 22(4), 1051–1057. https://doi.org/10.1017/s0033291700038629
Dunn, A. J. (2006). Effects of cytokines and infections on brain neurochemistry. Clinical Neuroscience Research, 6(1–2), 52–68. https://doi.org/10.1016/j.cnr.2006.04.002
Dyrbye, L. N., Massie, F. S., Eacker, A., Harper, W., Power, D., Durning, S. J., Thomas, M. R., Moutier, C., Satele, D., Sloan, J., & Shanafelt, T. D. (2010). Relationship between burnout and professional conduct and attitudes among US medical students. JAMA, 304(11), 1173–1180. https://doi.org/10.1001/jama.2010.1318
Dyrbye, L. N., Thomas, M. R., & Shanafelt, T. D. (2005). Medical student distress: Causes, consequences, and proposed solutions. Mayo Clinic Proceedings, 80(12), 1613–1622. https://doi.org/10.4065/80.12.1613
Dyrbye, L. N., Thomas, M. R., & Shanafelt, T. D. (2006). Systematic review of depression, anxiety, and other indicators of psychological distress among U.S. and Canadian medical students. Academic Medicine, 81(4), 354–373. https://doi.org/10.1097/00001888-200604000-00009
Edwards, K. M., Wilson, K. L., Sadja, J., Ziegler, M. G., & Mills, P. J. (2011). Effects on blood pressure and autonomic nervous system function of a 12-week exercise or exercise plus DASH-diet intervention in individuals with elevated blood pressure. Acta Physiologica, 203(3), 343–350. https://doi.org/10.1111/j.1748-1716.2011.02329.x
Eisenberg, D., Golberstein, E., & Hunt, J. (2009). Mental Health and Academic Success in College. The B. E. Journal of Economic Analysis & Policy, 9(1), Article 40. https://doi.org/10.2202/1935-1682.2191
Eisenhut, M. (2013). Neopterin in diagnosis and monitoring of infectious diseases. Journal of Biomarkers, 2013, Article 196432. https://doi.org/10.1155/2013/196432
Fares, J., Al Tabosh, H., Saadeddin, Z., El Mouhayyar, C., & Aridi, H. (2016). Stress, burnout and coping strategies in preclinical medical students. North American Journal of Medical Sciences, 8(2), 75–81. https://doi.org/10.4103/1947-2714.177299
Ferrari, A. J., Santomauro, D. F., Mantilla Herrera, A. M., Shadid, J., Ashbaugh, C., Erskine, H. E., Charlson, F. J., Degenhardt, L., Scott, J. G., McGrath, J. J., Allebeck, P., Benjet, C., Breitborde, N. J. K., Brugha, T., Dai, X., Dandona, L., Dandona, R., Fischer, F., Haagsma, J. A., … Whiteford, H. A. (2022). Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet Psychiatry, 9(2), 137–150. https://doi.org/10.1016/S2215-0366(21)00395-3
Forgione, F. A. (2018). Diagnostic dissent: Experiences of perceived misdiagnosis and stigma in persons diagnosed with schizophrenia. Journal of Humanistic Psychology, 59(1), 69–98. https://doi.org/10.1177/0022167818777151
Fuchs, D., Avanzas, P., Arroyo-Espliguero, R., Jenny, M., Consuegra-Sánchez, L., & Kaski, J. (2009). The role of neopterin in atherogenesis and cardiovascular risk assessment. Current Medicinal Chemistry, 16, 4644–4653. https://doi.org/10.2174/092986709789878247
Gao, K., Mu, C.-L., Farzi, A., & Zhu, W.-Y. (2020). Tryptophan metabolism: A link between the gut microbiota and brain. Advances in Nutrition, 11(3), 709–723. https://doi.org/10.1093/advances/nmz127
García-Gutiérrez, M. S., Navarrete, F., Sala, F., Gasparyan, A., Austrich-Olivares, A., & Manzanares, J. (2020). Biomarkers in psychiatry: Concept, definition, types and relevance to the clinical reality. Frontiers in Psychiatry, 11, Article 432. https://doi.org/10.3389/fpsyt.2020.00432
Gass, P., Reichardt, H. M., Strekalova, T., Henn, F., & Tronche, F. (2001). Mice with targeted mutations of glucocorticoid and mineralocorticoid receptors: Models for depression and anxiety? Physiology & Behavior, 73(5), 811–825. https://doi.org/10.1016/S0031-9384(01)00518-2
Ghisoni, K., de Paula Martins R., Barbeito, L., & Latini, A. (2015). Neopterin as a potential cytoprotective brain molecule. Journal of Psychiatric Research, 71, 134–139. https://doi.org/10.1016/j.jpsychires.2015.10.003
Gieseg, S. P., Baxter-Parker, G., & Lindsay, A. (2018). Neopterin, inflammation, and oxidative stress: What could we be missing? Antioxidants, 7(7), Article 80. https://doi.org/10.3390/antiox7070080
Godoy, L. D., Rossignoli, M. T., Delfino-Pereira, P., Garcia-Cairasco, N., & de Lima Umeoka, E. H. (2018). A comprehensive overview on stress neurobiology: Basic concepts and clinical implications. Frontiers in Behavioral Neuroscience, 12, Article 127. https://doi.org/10.3389/fnbeh.2018.00127
Goebert, D., Thompson, D., Takeshita, J., Beach, C., Bryson, P., Ephgrave, K., Kent, A., Kunkel, M., Schechter, J., & Tate, J. (2009). Depressive symptoms in medical students and residents: A multischool study. Academic Medicine, 84(2), 236–241. https://doi.org/10.1097/ACM.0b013e31819391bb
Gordan, R., Gwathmey, J. K., & Xie, L.-H. (2015). Autonomic and endocrine control of cardiovascular function. World Journal of Cardiology, 7(4), 204–214. https://doi.org/10.4330/wjc.v7.i4.204
Guest, P. C. (2017). Biomarkers and mental illness: It's not all in the mind. Copernicus Books.
Guy-Evans, O. (2021, April 13). Temporal lobe: Definition, functions, and location. Simple Psychology. Retrieved January 22. www.simplypsychology.org/temporal-lobe.html
Hamerlinck, F. F. V. (1999). Neopterin: A review. Experimental Dermatology, 8(3), 167–176. https://doi.org/10.1111/j.1600-0625.1999.tb00367.x
Handouzi, W., Maaoui, C., Pruski, A., & Moussaoui, A. (2014). Objective model assessment for short-term anxiety recognition from blood volume pulse signal. Biomedical Signal Processing and Control, 14, 217–227. https://doi.org/10.1016/j.bspc.2014.07.008
Haroon, E., Raison, C. L., & Miller, A. H. (2012). Psychoneuroimmunology meets neuropsychopharmacology: Translational implications of the impact of inflammation on behavior. Neuropsychopharmacology, 37(1), 137–162. https://doi.org/10.1038/npp.2011.205
Henry, J. D., & Crawford, J. R. (2005). The short-form version of the Depression Anxiety Stress Scales (DASS-21): Construct validity and normative data in a large non-clinical sample. British Journal of Clinical Psychology, 44(2), 227–239. https://doi.org/10.1348/014466505X29657
Hillebrand, S., Gast, K. B., de Mutsert, R., Swenne, C. A., Jukema, J. W., Middeldorp, S., Rosendaal, F. R., & Dekkers, O. M. (2013). Heart rate variability and first cardiovascular event in populations without known cardiovascular disease: Meta-analysis and dose–response meta-regression. EP Europace, 15(5), 742–749. https://doi.org/10.1093/europace/eus341
Ho, T. C., Pham, H. T., Miller, J. G., Kircanski, K., & Gotlib, I. H. (2020). Sympathetic nervous system dominance during stress recovery mediates associations between stress sensitivity and social anxiety symptoms in female adolescents. Development and Psychopathology, 32(5), 1914–1925. https://doi.org/10.1017/S0954579420001261
Hodes, G. E., Kana, V., Menard, C., Merad, M., & Russo, S. J. (2015). Neuroimmune mechanisms of depression. Nature Neuroscience, 18(10), 1386–1393. https://doi.org/10.1038/nn.4113
Hoehn–Saric, R., & McLeod, D. R. (1988). The peripheral sympathetic nervous system. Its role in normal and pathologic anxiety. Psychiatric Clinics of North America, 11(2), 375–386.
Hoge, E. A., Brandstetter, K., Moshier, S., Pollack, M. H., Wong, K. K., & Simon, N. M. (2009). Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder. Depression and Anxiety, 26(5), 447–455. https://doi.org/10.1002/da.20564
Hojat, M., Mangione, S., Nasca, T. J., Rattner, S., Erdmann, J. B., Gonnella, J. S., & Magee, M. (2004). An empirical study of decline in empathy in medical school. Medical Education, 38(9), 934–941. https://doi.org/10.1111/j.1365-2929.2004.01911.x
Holwerda, S. W., Luehrs, R. E., Gremaud, A. L., Wooldridge, N. A., Stroud, A. K., Fiedorowicz, J. G., Abboud, F. M., & Pierce, G. L. (2018). Relative burst amplitude of muscle sympathetic nerve activity is an indicator of altered sympathetic outflow in chronic anxiety. Journal of Neurophysiology, 120(1), 11–22. https://doi.org/10.1152/jn.00064.2018
Hourani, L. L., Davila, M. I., Morgan, J., Meleth, S., Ramirez, D., Lewis, G., Kizakevich, P. N., Eckhoff, R., Morgan, T., Strange, L., Lane, M., Weimer, B., & Lewis, A. (2020). Mental health, stress, and resilience correlates of heart rate variability among military reservists, guardsmen, and first responders. Physiology & Behavior, 214, Article 112734. https://doi.org/10.1016/j.physbeh.2019.112734
Huber, C., Batchelor, J. R., Fuchs, D., Hausen, A., Lang, A., Niederwieser, D., Reibnegger, G., Swetly, P., Troppmair, J., & Wachter, H. (1984). Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. Journal of Experimental Medicine, 160(1), 310–316. https://doi.org/10.1084/jem.160.1.310
Inserra, A., Mastronardi, C. A., Rogers, G., Licinio, J., & Wong, M. L. (2019). Neuroimmunomodulation in major depressive disorder: Focus on caspase 1, inducible nitric oxide synthase, and interferon-gamma. Molecular Neurobiology, 56(6), 4288–4305. https://doi.org/10.1007/s12035-018-1359-3
Jamil, H., Alakkari, M., Al-Mahini, M. S., Alsayid, M., & Al Jandali, O. (2022). The impact of anxiety and depression on academic performance: A cross-sectional study among medical students in Syria. Avicenna Journal of Medicine, 12(3), 111–119. https://doi.org/10.1055/s-0042-1755181
Jiang, L.-C., Yan, Y.-J., Jin, Z.-S., Hu, M.-L., Wang, L., Song, Y., Li, N.-N., Su, J., Wu, D.-X., & Xiao, T. (2020). The Depression Anxiety Stress Scale-21 in Chinese hospital workers: Reliability, latent structure, and measurement invariance across genders. Frontiers in Psychology, 11, Article 247. https://doi.org/10.3389/fpsyg.2020.00247
Johnson, J. D., Barnard, D. F., Kulp, A. C., & Mehta, D. M. (2019). Neuroendocrine regulation of brain cytokines after psychological stress. Journal of the Endocrine Society, 3(7), 1302–1320. https://doi.org/10.1210/js.2019-00053
Kanda, P. A. M., Anghinah, R., Smidth, M. T., & Silva, J. M. (2009). The clinical use of quantitative EEG in cognitive disorders. Dementia & Neuropsychologia, 3(3), 195–203. https://doi.org/10.1590/S1980-57642009DN30300004
Karason, K., Mølgaard, H., Wikstrand, J., & Sjöström, L. (1999). Heart rate variability in obesity and the effect of weight loss. The American Journal of Cardiology, 83(8), 1242–1247. https://doi.org/10.1016/s0002-9149(99)00066-1
Kemp, A. H., Quintana, D. S., Felmingham, K. L., Matthews, S., & Jelinek, H. F. (2012). Depression, comorbid anxiety disorders, and heart rate variability in physically healthy, unmedicated patients: implications for cardiovascular risk. PLoS ONE, 7(2), Article e30777. https://doi.org/10.1371/journal.pone.0030777
Kemp, A. H., Quintana, D. S., Gray, M. A., Felmingham, K. L., Brown, K., & Gatt, J. M. (2010). Impact of depression and antidepressant treatment on heart rate variability: A review and meta-analysis. Biological Psychiatry, 67(11), 1067–1074. https://doi.org/10.1016/j.biopsych.2009.12.012
Kessler, R. C. (1997). The effects of stressful life events on depression. Annual Review of Psychology, 48, 191–214. https://doi.org/10.1146/annurev.psych.48.1.191
Klaus, F., Guetter, K., Schlegel, R., Seifritz, E., Rassi, A., Thöny, B., Cathomas, F., & Kaiser, S. (2021). Peripheral biopterin and neopterin in schizophrenia and depression. Psychiatry Research, 297, Article 113745. https://doi.org/10.1016/j.psychres.2021.113745
Kreibig, S. (2010). Autonomic nervous system activity in emotion: A review. Biological Psychology, 84(3), 394–421. https://doi.org/10.1016/j.biopsycho.2010.03.010
Kubota, Y., Chen, L. Y., Whitsel, E. A., & Folsom, A. R. (2017). Heart rate variability and lifetime risk of cardiovascular disease: The atherosclerosis risk in communities study. Annals of Epidemiology, 27(10), 619–625.e2. https://doi.org/10.1016/j.annepidem.2017.08.024
Kudat, H., Akkaya, V., Sozen, A. B., Salman, S., Demirel, S., Ozcan, M., Atilgan, D., Yilmaz, M. T., & Guven, O. (2006). Heart rate variability in diabetes patients. Journal of International Medical Research, 34(3), 291–296. https://doi.org/10.1177/147323000603400308
Kushki, A., Fairley, J., Merja, S., King, G., & Chau, T. (2011). Comparison of blood volume pulse and skin conductance responses to mental and affective stimuli at different anatomical sites. Physiological Measurement, 32(10), 1529–1539. https://doi.org/10.1088/0967-3334/32/10/002
Lanser, L., Kink, P., Egger, E. M., Willenbacher, W., Fuchs, D., Weiss, G., & Kurz, K. (2020). Inflammation-induced tryptophan breakdown is related with anemia, fatigue, and depression in cancer. Frontiers in Immunology, 11, Article 249. https://doi.org/10.3389/fimmu.2020.00249
Lovibond, S. H., & Lovibond, P. F. (1995). Manual for the depression anxiety stress scales (2nd Ed.). Psychology Foundation of Australia.
Macaluso, M., & Preskorn, S. H. (2012). How biomarkers will change psychiatry: From clinical trials to practice. Part I: Introduction. Journal of Psychiatric Practice, 18(2), 118–121. https://doi.org/10.1097/01.pra.0000413277.11091.25
Maes, M., Scharpé, S., Meltzer, H. Y., Okayli, G., Bosmans, E., D'Hondt, P., Vanden Bossche, B. V., & Cosyns, P. (1994). Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: Further evidence for an immune response. Psychiatry Research, 54(2), 143–160. https://doi.org/10.1016/0165-1781(94)90003-5
Maes, M., Song, C., Lin, A., De Jongh, R., Van Gastel, A., Kenis, G., Bosmans, E., De Meester, I., Benoy, I., Neels, H., Demedts, P., Janca, A., Scharpé, S., & Smith, R. S. (1998). The effects of psychological stress on humans: Increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine, 10(4), 313–318. https://doi.org/10.1006/cyto.1997.0290
Maes, M., Van der Planken, M., Stevens, W. J., Peeters, D., DeClerck, L. S., Bridts, C. H., Schotte, C., & Cosyns, P. (1992). Leukocytosis, monocytosis and neutrophilia: Hallmarks of severe depression. Journal of Psychiatric Research, 26(2), 125–134. https://doi.org/10.1016/0022-3956(92)90004-8
Maggi, E., Parronchi, P., Manetti, R., Simonelli, C., Piccinni, M. P., Rugiu, F. S., De Carli, M., Ricci, M., & Romagnani, S. (1992). Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones. Journal of Immunology, 148(7), 2142–2147.
Malekshahi, A., Malekshahi, R., Czornik, M., Dax, J., Wolpert, S., Bauer, H., Braun, C., & Birbaumer, N. (2020). Real-time monitoring and regulating auditory cortex alpha activity in patients with chronic tinnitus. Journal of Neural Engineering, 17(1), Article 016032. https://doi.org/10.1088/1741-2552/ab57d5
Maser, B., Danilewitz, M., Guérin, E., Findlay, L., & Frank, E. (2019). Medical student psychological distress and mental illness relative to the general population: A Canadian cross-sectional survey. Academic Medicine, 94(11), 1781–1791. https://doi.org/10.1097/acm.0000000000002958
Mayberg, H. S. (1997). Limbic-cortical dysregulation: A proposed model of depression. The Journal of Neuropsychiatry and Clinical Neurosciences, 9(3), 471–481. https://doi.org/10.1176/jnp.9.3.471
Maydych, V. (2019). The interplay between stress, inflammation, and emotional attention: Relevance for depression. Frontiers in Neuroscience, 13, Article 384. https://doi.org/10.3389/fnins.2019.00384
McCraty, R., & Shaffer, F. (2015). Heart rate variability: New perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Global Advances in Integrative Medicine and Health, 4(1), 46–61. https://doi.org/10.7453/gahmj.2014.073
Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65(9), 732–741. https://doi.org/10.1016/j.biopsych.2008.11.029
Mitra, R., & Sapolsky, R. M. (2008). Acute corticosterone treatment is sufficient to induce anxiety and amygdaloid dendritic hypertrophy. Proceedings of the National Academy of Sciences of the United States of America, 105(14), 5573–5578. https://doi.org/10.1073/pnas.0705615105
Mohammad, M. (2021). Risk factors associated with stress, anxiety, and depression among university undergraduate students. AIMS Public Health, 8(1), 36–65. https://doi.org/10.3934/publichealth.2021004
Monteiro, S., Ferreira, F. M., Pinto, V., Roque, S., Morais, M., de Sá-Calçada, D., Mota, C., Correia-Neves, M., & Cerqueira, J. J. (2016). Absence of IFNγ promotes hippocampal plasticity and enhances cognitive performance. Translational Psychiatry, 6(1), Article e707. https://doi.org/10.1038/tp.2015.194
Müller, N., & Schwarz, M. J. (2007). The immune-mediated alteration of serotonin and glutamate: Towards an integrated view of depression. Molecular Psychiatry, 12(11), 988–1000. https://doi.org/10.1038/sj.mp.4002006
Myint, A. M., Bondy, B., Baghai, T. C., Eser, D., Nothdurfter, C., Schüle, C., Zill, P., Müller, N., Rupprecht, R., & Schwarz, M. J. (2013). Tryptophan metabolism and immunogenetics in major depression: A role for interferon-γ gene. Brain, Behavior, and Immunity, 31, 128–133. https://doi.org/10.1016/j.bbi.2013.04.003
Myint, A. M., & Kim, Y. K. (2003). Cytokine–serotonin interaction through IDO: A neurodegeneration hypothesis of depression. Medical Hypotheses, 61(5–6), 519–525. https://doi.org/10.1016/S0306-9877(03)00207-X
Nathan, C. F. (1986). Peroxide and pteridine: A hypothesis on the regulation of macrophage antimicrobial activity by interferon gamma. Interferon, 7, 125–143.
Neurofeedback Alliance. (2021). Understanding brain waves. https://neurofeedbackalliance.org/understanding-brain-waves/
Nutt, D. J., & Malizia, A. L. (2001). New insights into the role of the GABAA–benzodiazepine receptor in psychiatric disorder. The British Journal of Psychiatry, 179(5), 390–396. https://doi.org/10.1192/bjp.179.5.390
O'Connor, J. C., Lawson, M. A., André, C., Moreau, M., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R. (2009). Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Molecular Psychiatry, 14(5), 511–522. https://doi.org/10.1038/sj.mp.4002148
Osimo, E. F., Pillinger, T., Rodriguez, I. M., Khandaker, G. M., Pariante, C. M., & Howes, O. D. (2020). Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain Behavior, and Immunity, 87, 901–909. https://doi.org/10.1016/j.bbi.2020.02.010
Pace, T. W., & Miller, A. H. (2009). Cytokines and glucocorticoid receptor signaling. Relevance to major depression. Annals of the New York Academy of Sciences, 1179(1), 86–105. https://doi.org/10.1111/j.1749-6632.2009.04984.x
Pace, T. W. W., Hu, F., & Miller, A. H. (2007). Cytokine-effects on glucocorticoid receptor function: Relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain, Behavior, and Immunity, 21(1), 9–19. https://doi.org/10.1016/j.bbi.2006.08.009
Pacileo, M., Cirillo, P., De Rosa, S., Ucci, G., Petrillo, G., Musto D’Amore, S., Sasso, L., Maietta, P., Spagnuolo, R., & Chiariello, M. (2007). The role of neopterin in cardiovascular disease. Archivio Monaldi per Le Malattie Del Torace [Monaldi Archives for Chest Disease], 68(2), 68–73. https://doi.org/10.4081/monaldi.2007.454
Pêgo, J. M., Sousa, J. C., Almeida, O. F., & Sousa, N. (2010). Stress and the neuroendocrinology of anxiety disorders. In M. B. Stein & T. Steckler (Eds.), Behavioral neurobiology of anxiety and its treatment (pp. 97–118). Springer Science + Business Media. https://doi.org/10.1007/7854_2009_13
Peper, E., Harvey, R., Lin, I.-M., Tylova, H., & Moss, D. (2007). Is there more to blood volume pulse than heart rate variability, respiratory sinus arrhythmia, and cardiorespiratory synchrony? Biofeedback, 35, 54–61.
Perlstein, W. M., Elbert, T., & Stenger, V. A. (2002). Dissociation in human prefrontal cortex of affective influences on working memory-related activity. Proceedings of the National Academy of Sciences, 99(3), 1736–1741. https://doi.org/10.1073/pnas.241650598
Pinto, P. C. L., Marcelos, C. M., Mezzasalma, M. A., Osterne, F. J. V., de Melo Tavares de Lima, M. A., & Nardi, A. E. (2014). Tinnitus and its association with psychiatric disorders: Systematic review. The Journal of Laryngology & Otology, 128(8), 660–664. https://doi.org/10.1017/S0022215114001030
Quagliato, L. A., & Nardi, A. E. (2018). Cytokine alterations in panic disorder: A systematic review. Journal of Affective Disorders, 228, 91–96. https://doi.org/10.1016/j.jad.2017.11.094
Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends in Immunology, 27(1), 24–31. https://doi.org/10.1016/j.it.2005.11.006
Raison, C. L., & Miller, A. H. (2003). When not enough is too much: The role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. The American Journal of Psychiatry, 160(9), 1554–1565. https://doi.org/10.1176/appi.ajp.160.9.1554
Rajkumar, R. P. (2022). The correlates of government expenditure on mental health services: An analysis of data from 78 countries and regions. Cureus, 14(8), Article e28284. https://doi.org/10.7759/cureus.28284
Reader, B. F., Jarrett, B. L., McKim, D. B., Wohleb, E. S., Godbout, J. P., & Sheridan, J. F. (2015). Peripheral and central effects of repeated social defeat stress: Monocyte trafficking, microglial activation, and anxiety. Neuroscience, 289, 429–442. https://doi.org/10.1016/j.neuroscience.2015.01.001
Risbrough, V. B., & Stein, M. B. (2006). Role of corticotropin releasing factor in anxiety disorders: A translational research perspective. Hormones and Behavior, 50(4), 550–561. https://doi.org/10.1016/j.yhbeh.2006.06.019
Roffman, J. L. (2011). Biomarkers and personalized psychiatry. Harvard Review of Psychiatry, 19(3), 99–101. https://doi.org/10.3109/10673229.2011.586547
Rojas, G. M., Alvarez, C., Montoya, C. E., de la Iglesia-Vayá, M., Cisternas, J. E., & Gálvez, M. (2018). Study of resting-state functional connectivity networks using EEG electrodes position as seed. Frontiers in Neuroscience, 12, Article 235. https://doi.org/10.3389/fnins.2018.00235
Rössler, W. (2016). The stigma of mental disorders: A millennia-long history of social exclusion and prejudices. EMBO Rep, 17(9), 1250–1253. https://doi.org/10.15252/embr.201643041
Roth, G. A., Abate, D., Abate, K. H., Abay, S. M., Abbafati, C., Abbasi, N., Abbastabar, H., Abd-Allah, F., Abdela, J., Abdelalim, A., Abdollahpour, I., Abdulkader, R. S., Abebe, H. T., Abebe, M., Abebe, Z., Abejie, A. N., Abera, S. F., Abil, O. Z., Abraha, H. N., ... Murray, C. J. L. (2018). Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392(10159), 1736–1788. https://doi.org/10.1016/S0140-6736(18)32203-7
Salim, S. (2014). Oxidative stress and psychological disorders. Current Neuropharmacology, 12(2), 140–147. https://doi.org/10.2174/1570159x11666131120230309
Šalkevicius, J., Damaševičius, R., Maskeliunas, R., & Laukiene, I. (2019). Anxiety level recognition for virtual reality therapy system using physiological signals. Electronics, 8(9), Article 1039. https://doi.org/10.3390/electronics8091039
Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews, 21(1), 55–89. https://doi.org/10.1210/edrv.21.1.0389
Sarchiapone, M., Gramaglia, C., Iosue, M., Carli, V., Mandelli, L., Serretti, A., Marangon, D., & Zeppegno, P. (2018). The association between electrodermal activity (EDA), depression and suicidal behaviour: A systematic review and narrative synthesis. BMC Psychiatry, 18(1), Article 22. https://doi.org/10.1186/s12888-017-1551-4
Satyjeet, F., Naz, S., Kumar, V., Aung, N. H., Bansari, K., Irfan, S., & Rizwan, A. (2020). Psychological stress as a risk factor for cardiovascular disease: A case-control study. Cureus, 12(10), Article e10757. https://doi.org/10.7759/cureus.10757
Saxena, S., Sharan, P., & Saraceno, B. (2003). Budget and financing of mental health services: Baseline information on 89 countries from WH’'s project atlas. Journal of Mental Health Policy and Economics, 6(3), 135–143.
Schiweck, C., Piette, D., Berckmans, D., Claes, S., & Vrieze, E. (2019). Heart rate and high frequency heart rate variability during stress as biomarker for clinical depression. A systematic review. Psychological Medicine, 49(2), 200–211. https://doi.org/10.1017/S0033291718001988
Schlee, W., Schecklmann, M., Lehner, A., Kreuzer, P. M., Vielsmeier, V., Poeppl, T. B., & Langguth, B. (2014). Reduced variability of auditory alpha activity in chronic tinnitus. Neural Plasticity, 2014, Article 436146. https://doi.org/10.1155/2014/436146
Shaffer, F., & Ginsberg, J. P. (2017). An overview of heart rate variability metrics and norms. Frontiers in Public Health, 5, Article 258. https://doi.org/10.3389/fpubh.2017.00258
Shin, L. M., & Liberzon, I. (2010). The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology, 35(1), 169–191. https://doi.org/10.1038/npp.2009.83
Shinba, T. (2017). Major depressive disorder and generalized anxiety disorder show different autonomic dysregulations revealed by heart-rate variability analysis in first-onset drug-naïve patients without comorbidity. Psychiatry and Clinical Neurosciences, 71(2), 135–145. https://doi.org/10.1111/pcn.12494
Silverman, M. N., Pearce, B. D., Biron, C. A., & Miller, A. H. (2005). Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunology, 18(1), 41–78. https://doi.org/10.1089/vim.2005.18.41
Singla, S., Jhamb, S., Singh, K. D., & Kumar, A. (2020). Depression affects autonomic system of the body? Yes, it does! Journal of Education and Health Promotion, 9, Article 217. https://doi.org/10.4103%2Fjehp.jehp_627_19
Smith, S. M., & Vale, W. W. (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in Clinical Neuroscience, 8(4), 383–395. https://doi.org/10.31887/DCNS.2006.8.4/ssmith
Sroykham, W., & Wongsawat, Y. (2019). Effects of brain activity, morning salivary cortisol, and emotion regulation on cognitive impairment in elderly people. Medicine, 98(26), Article e16114. https://doi.org/10.1097/md.0000000000016114
Steimer, T. (2002). The biology of fear- and anxiety-related behaviors. Dialogues in Clinical Neuroscience, 4(3), 231–249. https://doi.org/10.31887/DCNS.2002.4.3/tsteimer
Strauß, A., Wöstmann, M., & Obleser, J. (2014). Cortical alpha oscillations as a tool for auditory selective inhibition. Frontiers in Human Neuroscience, 8, Article 350. https://doi.org/10.3389/fnhum.2014.00350
Tanaka, M., Yoshida, M., Emoto, H., & Ishii, H. (2000). Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: Basic studies. European Journal of Pharmacology, 405(1–3), 397–406. https://doi.org/10.1016/S0014-2999(00)00569-0
Teed, A. R., Feinstein, J. S., Puhl, M., Lapidus, R. C., Upshaw, V., Kuplicki, R. T., Bodurka, J., Ajijola, O. A., Kaye, W. H., Thompson, W. K., Paulus, M. P., & Khalsa, S. S. (2022). Association of generalized anxiety disorder with autonomic hypersensitivity and blunted ventromedial prefrontal cortex activity during peripheral adrenergic stimulation: A randomized clinical trial. JAMA Psychiatry, 79(4), 323–332. https://doi.org/10.1001/jamapsychiatry.2021.4225
Teplan, M. (2002). Fundamental of EEG measurement. Measurement Science Review, 2(2), 1–11.
Thomas, M. R., Dyrbye, L. N., Huntington, J. L., Lawson, K. L., Novotny, P. J., Sloan, J. A., & Shanafelt, T. D. (2007). How do distress and well-being relate to medical student empathy? A multicenter study. Journal of General Internal Medicine, 22(2), 177–183. https://doi.org/10.1007/s11606-006-0039-6
Tomlinson, M., Grimsrud, A. T., Stein, D. J., Williams, D. R., & Myer, L. (2009). The epidemiology of major depression in South Africa: Results from the South African stress and health study. South African Medical Journal, 99(5 Pt. 2), 367–373.
Tonsing, K. N. (2014). Psychometric properties and validation of Nepali version of the Depression Anxiety Stress Scales (DASS-21). Asian Journal of Psychiatry, 8, 63–66. https://doi.org/10.1016/j.ajp.2013.11.001
Torpy, J. M., Lynm, C., & Glass, R. M. (2007). Chronic stress and the heart. JAMA, 298(14), Article 1722. https://doi.org/10.1001/jama.298.14.1722
Torres-Platas, S. G., Cruceanu, C., Chen, G. G., Turecki, G., & Mechawar, N. (2014). Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain, Behavior, and Immunity, 42, 50–59. https://doi.org/10.1016/j.bbi.2014.05.007
Tran, T. D., Tran, T., & Fisher, J. (2013). Validation of the depression anxiety stress scales (DASS) 21 as a screening instrument for depression and anxiety in a rural community-based cohort of northern Vietnamese women. BMC Psychiatry, 13(1), Article 24. https://doi.org/10.1186/1471-244X-13-24
Trivedi, J. K. (2006). Cognitive deficits in psychiatric disorders: Current status. Indian Journal of Psychiatry, 48(1), 10–20. https://doi.org/10.4103/0019-5545.31613
Valkanova, V., Ebmeier, K. P., & Allan, C. L. (2013). CRP, IL-6 and depression: A systematic review and meta-analysis of longitudinal studies. Journal of Affective Disorders, 150(3), 736–744. https://doi.org/10.1016/j.jad.2013.06.004
Vitasari, P., Wahab, M. N. A., Othman, A., Herawan, T., & Sinnadurai, S. K. (2010). the relationship between study anxiety and academic performance among engineering students. Procedia - Social and Behavioral Sciences, 8, 490–497. https://doi.org/10.1016/j.sbspro.2010.12.067
Vogelzangs, N., Beekman, A. T., de Jonge, P., & Penninx, B. W. (2013). Anxiety disorders and inflammation in a large adult cohort. Translational Psychiatry, 3(4), Article e249. https://doi.org/10.1038/tp.2013.27
Vogelzangs, N., Seldenrijk, A., Beekman, A. T. F., van Hout, H. P. J., de Jonge, P., & Penninx, B. W. J. H. (2010). Cardiovascular disease in persons with depressive and anxiety disorders. Journal of Affective Disorders, 125(1–3), 241–248. https://doi.org/10.1016/j.jad.2010.02.112
Von Känel, R., Hepp, U., Kraemer, B., Traber, R., Keel, M., Mica, L., & Schnyder, U. (2007). Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. Journal of Psychiatric Research, 41(9), 744–752. https://doi.org/10.1016/j.jpsychires.2006.06.009
Wagner, F., Wagner, R. G., Kolanisi, U., Makuapane, L. P., Masango, M., & Gómez-Olivé, F. X. (2022). The relationship between depression symptoms and academic performance among first-year undergraduate students at a South African university: A cross-sectional study. BMC Public Health, 22(1), Article 2067. https://doi.org/10.1186/s12889-022-14517-7
Wakefield, J. C. (2010). Misdiagnosing normality: Psychiatry's failure to address the problem of false positive diagnoses of mental disorder in a changing professional environment. Journal of Mental Health, 19(4), 337–351. https://doi.org/10.3109/09638237.2010.492418
Warner, S. (2013). Cheat sheet for neurofeedback. Stress Therapy Solutions. Retrieved January 23. https://stresstherapysolutions.com/uploads/STSCheatSheetoftheBrain.pdf
Watanabe, M. (2017). [Brodmann Areas 8 and 9 Including the Frontal Eye Field]. Brain and Nerve, 69(4), 347–354. https://doi.org/10.11477/mf.1416200751
Weinstock, M. (2001). Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Progress in Neurobiology, 65(5), 427–451. https://doi.org/10.1016/s0301-0082(01)00018-1
Weiss, C., Murr, C., Zoller, H., Haun, M., Widner,B., Ludescher, C., & Fuchs, D. (1999). Modulation of neopterin formation and tryptophan degradation by Th1- and Th2-derived cytokines in human monocytic cells. Clinical & Experimental Immunology, 116(3), 435–440. https://doi.org/10.1046/j.1365-2249.1999.00910.x
Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., Ferrari, A. J., Erskine, H. E., Charlson, F. J., Norman, R. E., Flaxman, A. D., Johns, N., Burstein, R., Murray, C. J. L., & Vos, T. (2013). Global burden of disease attributable to mental and substance use disorders: Findings from the Global Burden of Disease Study 2010. Lancet, 382(9904), 1575–1586. https://doi.org/10.1016/S0140-6736(13)61611-6
Widner, B., Laich, A., Sperner-Unterweger, B., Ledochowski, M., & Fuchs, D. (2002). Neopterin production, tryptophan degradation, and mental depression—What is the link? Brain Behavior and Immunity, 16(5), 590–595. https://doi.org/10.1016/S0889-1591(02)00006-5
Wilmer, M. T., Anderson, K., & Reynolds, M. (2021). Correlates of quality of life in anxiety disorders: Review of recent research. Current Psychiatry Reports, 23(11), Article 77. https://doi.org/10.1007/s11920-021-01290-4
Wohleb, E. S., Powell, N. D., Godbout, J. P., & Sheridan, J. F. (2013). Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. Journal of Neuroscience, 33(34), 13820–13833. https://doi.org/10.1523/jneurosci.1671-13.2013
Yang, X., Fang, Y., Chen, H., Zhang, T., Yin, X., Man, J., Yang, L., & Lu, M. (2021). Global, regional and national burden of anxiety disorders from 1990 to 2019: Results from the Global Burden of Disease Study 2019. Epidemiology and Psychiatric Sciences, 30, Article e36. https://doi.org/10.1017/s2045796021000275
Zöger, S., Svedlund, J., & Holgers, K.-M. (2006). Relationship between tinnitus severity and psychiatric disorders. Psychosomatics, 47(4), 282–288. https://doi.org/10.1176/appi.psy.47.4.282
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Rouxzan Cronje, Johanni Beukes, Andries Masenge, Peet du Toit, Priyesh Bipath
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (CC-BY) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
