Autonomic nervous system; Chronic stress; Cortisol; HPA axis; Medically-unexplained symptoms; Somatization; Neuropsychology and Physiological Psychology; General Neuroscience
Abstract :
[en] The positive feedback model of medically-unexplained symptoms posits that chronic stress affects the activity of the physiological stress axes, which in turn generates medically-unexplained symptoms. As a first step to empirically test its model assumptions, we investigated potential associations between chronic stress, physiological stress axis activity and medically-unexplained in a cross-sectional study. One hundred-ninety-nine healthy individuals provided self-reports on chronic stress and medically-unexplained symptoms, resting heart rate/variability (HR/HRV; e.g., root mean square of successive differences/RMSSD, low frequency/LF power), cortisol awakening response (CAR) and diurnal cortisol. Significant positive contributors to medically-unexplained symptoms were the chronic stress scales 'lack of social appreciation' and 'chronic worries', as well as CAR and LF HRV; diurnal cortisol was a negative contributor. Mediation analyses showed that the impact of neural indicators associated with physiological stress axis activity (HR/HRV) related to medically-unexplained symptoms, which was mediated by chronic stress, whereas the mediation effect as suggested by the positive feedback model was not significant. These cross-sectional findings do not support the positive feedback model. Longitudinal studies are required to conclude about potential mechanistic and causal relationships in the model. Nevertheless, our mediation analyses give first indication that the constitution of physiological stress axes may play a major role in how stressors are perceived and which kind of health-consequences (e.g., medically-unexplained symptoms) this may have.
Disciplines :
Neurosciences & behavior
Author, co-author :
SCHULZ, André ; University of Luxembourg > Faculty of Humanities, Education and Social Sciences (FHSE) > Department of Behavioural and Cognitive Sciences (DBCS) > Health and Behaviour
Larra, Mauro F; Division of Clinical Psychophysiology, Institute of Psychobiology, Trier University, Trier, Germany, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany
VÖGELE, Claus ; University of Luxembourg > Faculty of Humanities, Education and Social Sciences (FHSE) > Department of Behavioural and Cognitive Sciences (DBCS) > Health and Behaviour
Kölsch, Monika; Division of Clinical Psychophysiology, Institute of Psychobiology, Trier University, Trier, Germany
Schächinger, Hartmut; Division of Clinical Psychophysiology, Institute of Psychobiology, Trier University, Trier, Germany
External co-authors :
yes
Language :
English
Title :
The relationship between self-reported chronic stress, physiological stress axis dysregulation and medically-unexplained symptoms.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV. 2000, American Psychiatric Publishing, Inc https://doi.org/10.1176.
American Psychiatric Association, 2013. American Psychiatric Publishing, Inc, American.
Anderson, R.U., Orenberg, E.K., Morey, A., Chavez, N., Chan, C.A., Stress induced hypothalamus-pituitary-adrenal axis responses and disturbances in psychological profiles in men with chronic prostatitis/chronic pelvic pain syndrome. Journal of Urology 182:5 (2009), 2319–2324, 10.1016/j.juro.2009.07.042.
Andreassi, J.L., Psychophysiology – Human Behavior and Physiological Response, Third ed., 1995, Lawrence.
Arsalan, A., Majid, M., Human stress classification during public speaking using physiological signals. Computers in Biology and Medicine, 133, 2021, 104377, 10.1016/j.compbiomed.2021.104377.
Bauer, I., Hartkopf, J., Wikstrom, A.K., Schaal, N.K., Preissl, H., Derntl, B., Schleger, F., Acute relaxation during pregnancy leads to a reduction in maternal electrodermal activity and self-reported stress levels. BMC Pregnancy Childbirth, 21(1), 2021, 628, 10.1186/s12884-021-04099-4.
Bauer, M.E., Wieck, A., Lopes, R.P., Teixeira, A.L., Grassi-Oliveira, R., Interplay between neuroimmunoendocrine systems during post-traumatic stress disorder: A minireview. Neuroimmunomodulation 17:3 (2010), 192–195, 10.1159/000258721.
Berntson, G.G., Bigger, J.T. Jr., Eckberg, D.L., Grossman, P., Kaufmann, P.G., Malik, M., Nagaraja, H.N., Porges, S.W., Saul, J.P., Stone, P.H., van der Molen, M.W., Heart rate variability: Origins, methods, and interpretive caveats. Psychophysiology 34:6 (1997), 623–648, 10.1111/j.1469-8986.1997.tb02140.x.
Böhmelt, A.H., Nater, U.M., Franke S., Hellhammer D.H. and Ehlert, U. (2005). Basal and stimulated hypothalamic-pituitary-adrenal axis activity in patients with functional gastrointestinal disorders and healthy controls. Psychosomatic Medicine. 2005:67(2) pp. 288-294
Brosschot, J.F., Van Dijk, E., Thayer, J.F., Daily worry is related to low heart rate variability during waking and the subsequent nocturnal sleep period. International Journal of Psychophysiology 63:1 (2007), 39–47, 10.1016/j.ijpsycho.2006.07.016.
Chalmers, J.A., Heathers, J.A., Abbott, M.J., Kemp, A.H., Quintana, D.S., Worry is associated with robust reductions in heart rate variability: A transdiagnostic study of anxiety psychopathology. BMC Psychology, 4(1), 2016, 32, 10.1186/s40359-016-0138-z.
Chandola, T., Heraclides, A., Kumari, M., Psychophysiological biomarkers of workplace stressors. Neuroscience & Biobehaviroal Reviews 35:1 (2010), 51–57, 10.1016/j.neubiorev.2009.11.005.
Chrousos, G.P., Stress and disorders of the stress system. Nature Reviews Endocrinology 5:7 (2009), 374–381, 10.1038/nrendo.2009.106.
de Geus, E.J.C., Gianaros, P.J., Brindle, R.C., Jennings, J.R., Berntson, G.G., Should heart rate variability be “corrected” for heart rate? Biological, quantitative, and interpretive considerations. Psychophysiology, 56(2), 2019, e13287, 10.1111/psyp.13287.
Dressendorfer, R.A., Kirschbaum, C., Rohde, W., Stahl, F., Strasburger, C.J., Synthesis of a cortisol-biotin conjugate and evaluation as a tracer in an immunoassay for salivary cortisol measurement. Journal of Steroid Biochemistry and Molecular Biology 43:7 (1992), 683–692, 10.1016/0960-0760(92)90294-S.
Farmer, D.G., Dutschmann, M., Paton, J.F., Pickering, A.E., McAllen, R.M., Brainstem sources of cardiac vagal tone and respiratory sinus arrhythmia. Journal of Physiology 594:24 (2016), 7249–7265, 10.1113/JP273164.
Feussner, O., Rehnisch, C., Rabkow, N., Watzke, S., Somatization symptoms-prevalence and risk, stress and resilience factors among medical and dental students at a mid-sized German university. PeerJ, 10, 2022, e13803, 10.7717/peerj.13803.
Fischer, S., Doerr, J.M., Strahler, J., Mewes, R., Thieme, K., Nater, U.M., Stress exacerbates pain in the everyday lives of women with fibromyalgia syndrome–The role of cortisol and alpha-amylase. Psychoneuroendocrinology 63 (2016), 68–77, 10.1016/j.psyneuen.2015.09.018.
Fischer, S., Skoluda, N., Ali, N., Nater, U.M., Mewes, R., Hair cortisol levels in women with medically unexplained symptoms. Journal of Psychiatric Research 146 (2022), 77–82, 10.1016/j.jpsychires.2021.12.044.
Fries, E., Hesse, J., Hellhammer, J., Hellhammer, D.H., A new view on hypocortisolism. Psychoneuroendocrinology 30:10 (2005), 1010–1016, 10.1016/j.psyneuen.2005.04.006.
Gallo, L.C., Roesch, S.C., Fortmann, A.L., Carnethon, M.R., Penedo, F.J., Perreira, K., Birnbaum-Weitzman, O., Wassertheil-Smoller, S., Castaneda, S.F., Talavera, G.A., Sotres-Alvarez, D., Daviglus, M.L., Schneiderman, N., Isasi, C.R., Associations of chronic stress burden, perceived stress, and traumatic stress with cardiovascular disease prevalence and risk factors in the hispanic community health study/study of latinos sociocultural ancillary study. Psychosomatic Medicine 76:6 (2014), 468–475, 10.1097/PSY.0000000000000069.
Gouin, J.P., Wenzel, K., Boucetta, S., O'Byrne, J., Salimi, A., Dang-Vu, T.T., High-frequency heart rate variability during worry predicts stress-related increases in sleep disturbances. Sleeping Medicine 16:5 (2015), 659–664, 10.1016/j.sleep.2015.02.001.
Grossman, P., Kollai, M., Respiratory sinus arrhythmia, cardiac vagal tone, and respiration: within- and between-individual relations. Psychophysiology 30:5 (1993), 486–495, 10.1111/j.1469-8986.1993.tb02072.x.
Hayes, A.F., Introduction to mediation, moderation, and conditional process analysis: A regression-based approach, Second ed., 2018, Guilford.
Heim, C., Ehlert, U., Hanker, J.P., Hellhammer, D.H., Abuse-related posttraumatic stress disorder and alterations of the hypothalamic-pituitary-adrenal axis in women with chronic pelvic pain. Psychosomatic Medicine 60:3 (1998), 309–318 〈http://www.ncbi.nlm.nih.gov/pubmed/9625218〉.
Heim, C., Ehlert, U., Hellhammer, D.H., The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 25:1 (2000), 1–35, 10.1016/S0306-4530(99)00035-9.
Hellhammer, J., Fries, E., Schweisthal, O.W., Schlotz, W., Stone, A.A., Hagemann, D., Several daily measurements are necessary to reliably assess the cortisol rise after awakening: State- and trait components. Psychoneuroendocrinology 32:1 (2007), 80–86, 10.1016/j.psyneuen.2006.10.005.
Hilderink, P.H., Collard, R., Rosmalen, J.G., Oude Voshaar, R.C., Prevalence of somatoform disorders and medically unexplained symptoms in old age populations in comparison with younger age groups: A systematic review. Ageing Research Review 12:1 (2013), 151–156, 10.1016/j.arr.2012.04.004.
Hiller, W., Rief, W., Brahler, E., Somatization in the population: from mild bodily misperceptions to disabling symptoms. Social Psychiatry and Psychiatric Epidemiology 41:9 (2006), 704–712, 10.1007/s00127-006-0082-y.
Huggenberger, H.J., Suter, S.E., Blumenthal, T.D., Schächinger, H., Maternal social stress modulates the development of prepulse inhibition of startle in infants. Developmental Cognitive Neuroscientists 3 (2013), 84–90, 10.1016/j.dcn.2012.09.006.
Hüsing, P., Löwe, B., Toussaint, A., Comparing the diagnostic concepts of ICD-10 somatoform disorders and DSM-5 somatic symptom disorders in patients from a psychosomatic outpatient clinic. Journal of Psychosomatic Research 113 (2018), 74–80, 10.1016/j.jpsychores.2018.08.001.
Laederach-Hofmann, K., Rüddel, H., Mussgay, L., Pathological baroreceptor sensitivity in patients suffering from somatization disorders: Do they correlate with symptoms?. Biological Psychology 79:2 (2008), 243–249 〈http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18611426〉.
Larra, M.F., Schulz, A., Schilling, T.M., Ferreira de Sa, D.S., Best, D., Kozik, B., Schächinger, H., Heart rate response to post-learning stress predicts memory consolidation. Neurobiology of Learning Memory 109C (2014), 74–81, 10.1016/j.nlm.2013.12.004.
Lazarus, R.S., Folkman, S., Stress, appraisal, and coping. 1984, Springer.
Li-Tempel, T., Larra, M.F., Sandt, E., Meriaux, S.B., Schote, A.B., Schachinger, H., Muller, C.P., Turner, J.D., The cardiovascular and hypothalamus-pituitary-adrenal axis response to stress is controlled by glucocorticoid receptor sequence variants and promoter methylation. Clinical Epigenetics, 8, 2016, 12, 10.1186/s13148-016-0180-y.
Li-Tempel, T., Larra, M.F., Winnikes, U., Tempel, T., DeRijk, R.H., Schulz, A., Schachinger, H., Meyer, J., Schote, A.B., Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress. Biological Psychology 119 (2016), 112–121, 10.1016/j.biopsycho.2016.07.010.
Lieb, R., Meinlschmidt, G., Araya, R., Epidemiology of the association between somatoform disorders and anxiety and depressive disorders: an update. Psychosomatic Medicine 69:9 (2007), 860–863, 10.1097/PSY.0b013e31815b0103.
Mayer, K.N., Ghadri, J.R., Jaguszewski, M., Scherff, F., Saguner, A.M., Kazemian, E., Baumann, C.R., Jenewein, J., Tsakiris, M., Lüscher, T.F., Brugger, P., Templin, C., Takotsubo syndrome – A close connection to the brain: A prospective study investigating neuropsychiatric traits. IJC Metabolic & Endocrine 12 (2016), 36–41, 10.1016/j.ijcme.2016.06.001.
McEwen, B.S., The neurobiology of stress: From serendipity to clinical relevance. Brain Research 886:1–2 (2000), 172–189, 10.1016/S0006-8993(00)02950-4.
Mellner, C., Krantz, G., Lundberg, U., Medically unexplained symptoms in women as related to physiological stress responses. Stress & Health 21:1 (2004), 45–52, 10.1002/smi.1037.
Mewes, R., Feneberg, A.C., Doerr, J.M., Nater, U.M., Psychobiological mechanisms in somatic symptom disorder and depressive disorders: An ecological momentary assessment approach. Psychosomatic Medicine 84:1 (2022), 86–96, 10.1097/PSY.0000000000001006.
Milde-Busch, A., Blaschek, A., Heinen, F., Borggrafe, I., Koerte, I., Straube, A., Schankin, C., von Kries, R., Associations between stress and migraine and tension-type headache: Results from a school-based study in adolescents from grammar schools in Germany. Cephalalgia 31:7 (2011), 774–785, 10.1177/0333102410390397.
Nolan, J., Batin, P.D., Andrews, R., Lindsay, S.J., Brooksby, P., Mullen, M., Baig, W., Flapan, A.D., Cowley, A., Prescott, R.J., Neilson, J.M., Fox, K.A., Prospective study of heart rate variability and mortality in chronic heart failure: Results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation 98:15 (1998), 1510–1516, 10.1161/01.cir.98.15.1510.
Pagani, M., Montano, N., Porta, A., Malliani, A., Abboud, F.M., Birkett, C., Somers, V.K., Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation 95:6 (1997), 1441–1448, 10.1161/01.CIR.95.6.1441.
Pedrosa Gil, F., Bidlingmaier, M., Ridout, N., Scheidt, C.E., Caton, S., Schoechlin, C., Nickel, M., The relationship between alexithymia and salivary cortisol levels in somatoform disorders. Nordic Journal of Psychiatry 62:5 (2008), 366–373, 10.1080/08039480801983554.
Penz, M., Stalder, T., Miller, R., Ludwig, V.M., Kanthak, M.K., Kirschbaum, C., Hair cortisol as a biological marker for burnout symptomatology. Psychoneuroendocrinology 87 (2018), 218–221, 10.1016/j.psyneuen.2017.07.485.
Petrowski, K., Herhaus, B., Schoniger, C., Frank, M., Pyrc, J., Stress load of emergency service: Effects on the CAR and HRV of HEMS emergency physicians on different working days (N = 20). International Archives of Occupational and Environmental Health 92:2 (2019), 155–164, 10.1007/s00420-018-1362-z.
Pieritz, K., Schafer, S.J., Strahler, J., Rief, W., Euteneuer, F., Chronic stress moderates the impact of social exclusion on pain tolerance: An experimental investigation. Journal of Pain Research 10 (2017), 1155–1162, 10.2147/JPR.S129872.
Pollatos, O., Herbert, B.M., Wankner, S., Dietel, A., Wachsmuth, C., Henningsen, P., Sack, M., Autonomic imbalance is associated with reduced facial recognition in somatoform disorders. Journal of Psychosomatic Research 71:4 (2011), 232–239, 10.1016/j.jpsychores.2011.03.012.
Pruessner, J.C., Kirschbaum, C., Meinlschmid, G., Hellhammer, D.H., Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28:7 (2003), 916–931, 10.1016/S0306-4530(02)00108-7.
Pruessner, M., Hellhammer, D.H., Pruessner, J.C., Lupien, S.J., Self-reported depressive symptoms and stress levels in healthy young men: Associations with the cortisol response to awakening. Psychosomatic Medicine 65:1 (2003), 92–99, 10.1097/01.psy.0000040950.22044.10.
Reyes del Paso, G.A., Langewitz, W., Mulder, L.J., van Roon, A., Duschek, S., The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: A review with emphasis on a reanalysis of previous studies. Psychophysiology 50:5 (2013), 477–487, 10.1111/psyp.12027.
Rief, W., Auer, C., Cortisol and somatization. Biological Psychological 53:1 (2000), 13–23, 10.1016/s0301-0511(00)00042-9.
Rief, W., Barsky, A.J., Psychobiological perspectives on somatoform disorders. Psychoneuroendocrinology 30:10 (2005), 996–1002, 10.1016/j.psyneuen.2005.03.018.
Rief, W., Broadbent, E., Explaining medically unexplained symptoms-models and mechanisms. Clinical Psychology Review 27:7 (2007), 821–841, 10.1016/j.cpr.2007.07.005.
Rief, W., Hennings, A., Riemer, S., Euteneuer, F., Psychobiological differences between depression and somatization. Journal of Psychosomatic Research 68:5 (2010), 495–502, 10.1016/j.jpsychores.2010.02.001.
Rief, W., Hessel, A., Braehler, E., Somatization symptoms and hypochondriacal features in the general population. Psychosomatic Medicine 63:4 (2001), 595–602 〈http://www.ncbi.nlm.nih.gov/pubmed/11485113〉.
Rief, W., Hiller, W., Screening für Somatoforme Störungen. 2008, Hogrefe.
Rief, W., Shaw, R., Fichter, M.M., Elevated levels of psychophysiological arousal and cortisol in patients with somatization syndrome. Psychosomatic Medicine 60:2 (1998), 198–203 〈http://www.ncbi.nlm.nih.gov/pubmed/9560870〉.
Roelofs, K., Spinhoven, P., Trauma and medically unexplained symptoms towards an integration of cognitive and neuro-biological accounts. Clinical Psychology Review 27:7 (2007), 798–820, 10.1016/j.cpr.2007.07.004.
Rucker, D.R., Preacher, K.J., Tormala, Z.L., Petty, R.E., Mediation analysis in social psychology: Current practices and new recommendations. Social and Personality Psychology Compass 5:6 (2011), 359–371, 10.1111/j.1751-9004.2011.00355.x.
Schaaf, H., Flohre, S., Hesse, G., Gieler, U., [Chronic stress as an influencing factor in tinnitus patients]. HNO 62:2 (2014), 108–114, 10.1007/s00106-013-2798-9 (Chronischer Stress als Einflussgrosse bei Tinnituspatienten.).
Schächinger, H., Weinbacher, M., Kiss, A., Ritz, R., Langewitz, W., Cardiovascular indices of peripheral and central sympathetic activation. Psychosomatic Medicine 63:5 (2001), 788–796, 10.1097/00006842-200109000-00012.
Schlotz, W., Hellhammer, J., Schulz, P., Stone, A.A., Perceived work overload and chronic worrying predict weekend-weekday differences in the cortisol awakening response. Psychosomatic Medicine 66:2 (2004), 207–214 〈http://www.ncbi.nlm.nih.gov/pubmed/15039505〉.
Schmid, D.M., Reitz, A., Curt, A., Hauri, D., Schurch, B., Urethral evoked sympathetic skin responses and viscerosensory evoked potentials as diagnostic tools to evaluate urogenital autonomic afferent innervation in spinal cord injured patients. Journal of Urology 171:3 (2004), 1156–1160, 10.1097/01.ju.0000111809.81966.8b.
Schultchen, D., Bayer, J., Kuhnel, J., Melchers, K.G., Pollatos, O., Interoceptive accuracy is related to long-term stress via self-regulation. Psychophysiology, 56(10), 2019, e13429, 10.1111/psyp.13429.
Schulz, A., Dierolf, A.M., Lutz, A.P.C., Voderholzer, U., Koch, S., Bach, M., Asenstorfer, C., Michaux, G., Mertens, V.C., Vögele, C., Higher cardiovascular activation, but normal heartbeat-evoked potentials and cardiac interoceptive accuracy in somatoform disorders and major depressive disorder. Psychiatry Research Communications, 2(3), 2022, 100052, 10.1016/j.psycom.2022.100052.
Schulz, A., Rost, S., Flasinski, T., Dierolf, A.M., Lutz, A.P.C., Münch, E.E., Mertens, V.C., Witthöft, M., Vögele, C., Distinctive body perception mechanisms in high versus low symptom reporters: A neurophysiological model for medically-unexplained symptoms. Journal of Psychosomatic Research, 137, 2020, 110223, 10.1016/j.jpsychores.2020.110223.
Schulz, A., Schultchen, D., Vögele, C., Interoception, stress, and physical symptoms in stress-associated diseases. European Journal of Health Psychology 27 (2020), 132–153.
Schulz, A., Strelzyk, F., Ferreira de Sa, D.S., Naumann, E., Vögele, C., Schächinger, H., Cortisol rapidly affects amplitudes of heartbeat-evoked brain potentials-Implications for the contribution of stress to an altered perception of physical sensations?. Psychoneuroendocrinology 38:11 (2013), 2686–2693, 10.1016/j.psyneuen.2013.06.027.
Schulz, A., Vögele, C., Interoception and stress. Frontiers in Psychology, 6, 2015, 993, 10.3389/fpsyg.2015.00993.
Schulz, P., Kirschbaum, C., Pruessner, J., Hellhammer, D., Increased free cortisol secretion after awakening in chronically stressed individuals due to work overload. Stress & Health 14:2 (1998), 91–97, 10.1002/(SICI)1099-1700(199804)14:2<91::AID-SMI765>3.0.CO;2-S.
Schulz, P., Schlotz, W., Becker, P., TICS. Trierer Inventar zu chronischem Stress. 2004, Hogrefe.
Stalder, T., Kirschbaum, C., Kudielka, B.M., Adam, E.K., Pruessner, J.C., Wüst, S., Clow, A., Assessment of the cortisol awakening response: Expert consensus guidelines. Psychoneuroendocrinology 63 (2016), 414–432, 10.1016/j.psyneuen.2015.10.010.
Strahler, J., Ziegert, T., Psychobiological stress response to a simulated school shooting in police officers. Psychoneuroendocrinology 51 (2015), 80–91, 10.1016/j.psyneuen.2014.09.016.
Tafet, G.E., Bernardini, R., Psychoneuroendocrinological links between chronic stress and depression [Review]. Progress in neuro-Psychopharmacology & Biological Psychiatry 27:6 (2003), 893–903, 10.1016/S0278-5846(03)00162-3.
TaskForce, Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. European Heart Journal 17:3 (1996), 354–381, 10.1093/oxfordjournals.eurheartj.a014868.
Thayer, J.F., Yamamoto, S.S., Brosschot, J.F., The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. International Journal of Cardiology 141:2 (2010), 122–131, 10.1016/j.ijcard.2009.09.543.
van Leeuwen, N., Bellingrath, S., de Kloet, E.R., Zitman, F.G., DeRijk, R.H., Kudielka, B.M., Wüst, S., Human mineralocorticoid receptor (MR) gene haplotypes modulate MR expression and transactivation: Implication for the stress response. Psychoneuroendocrinology 36:5 (2011), 699–709, 10.1016/j.psyneuen.2010.10.003.
Vedhara, K., Cox, N.K., Wilcock, G.K., Perks, P., Hunt, M., Anderson, S., Lightman, S.L., Shanks, N.M., Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 353:9153 (1999), 627–631, 10.1016/S0140-6736(98)06098-X.
Vreijling, S.R., Troudart, Y., Brosschot, J.F., Reduced heart rate variability in patients with medically unexplained physical symptoms: A Meta-Analysis of HF-HRV and RMSSD. Psychosomatic Medicine 83:1 (2021), 2–15, 10.1097/PSY.0000000000000874.
Vrijkotte, T.G., van Doornen, L.J., de Geus, E.J., Overcommitment to work is associated with changes in cardiac sympathetic regulation [Research Support, Non-U.S. Gov't]. Psychosomatic Medicine 66:5 (2004), 656–663, 10.1097/01.psy.0000138283.65547.78.
Wilhelm, I., Born, J., Kudielka, B.M., Schlotz, W., Wüst, S., Is the cortisol awakening rise a response to awakening?. Psychoneuroendocrinology 32:4 (2007), 358–366, 10.1016/j.psyneuen.2007.01.008.
Ying-Chih, C., Yu-Chen, H., Wei-Lieh, H., Heart rate variability in patients with somatic symptom disorders and functional somatic syndromes: A systematic review and meta-analysis. Neuroscience & Biobehaviroal Reviews 112 (2020), 336–344, 10.1016/j.neubiorev.2020.02.007.
Zhao, X., Lynch, J.G., Chen, Q., Reconsidering Baron and Kenny: Myths and truths about mediation analysis. Journal of Consumer Research 37 (2010), 197–206, 10.1086/651257.
