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Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome

Published online by Cambridge University Press:  06 September 2007

F. Van Den Eede ,
G. Moorkens ,
W. Hulstijn ,
B. Van Houdenhove ,
P. Cosyns ,
B. G. C. Sabbe  and
S. J. Claes
F. Van Den Eede
Affiliation:
Department of Psychiatry, Antwerp University Hospital, Edegem, Belgium Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium Department of Molecular Genetics VIB8, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium
G. Moorkens
Affiliation:
Department of Internal Medicine, Antwerp University Hospital, Edegem, Belgium
W. Hulstijn
Affiliation:
Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium
B. Van Houdenhove
Affiliation:
Department of Psychiatry, University Hospital Gasthuisberg, Leuven, Belgium
P. Cosyns
Affiliation:
Department of Psychiatry, Antwerp University Hospital, Edegem, Belgium Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium
B. G. C. Sabbe
Affiliation:
Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium Psychiatric Hospital St.-Norbertushuis, Duffel, Belgium
S. J. Claes*
Affiliation:
Department of Molecular Genetics VIB8, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium Department of Psychiatry, University Hospital Gasthuisberg, Leuven, Belgium
*
*Address for correspondence: Professor S. J. Claes, M.D., Ph.D., Department of Psychiatry, University Hospital Gasthuisberg, Herestraat 49, B-3000Leuven, Belgium. (Email: Stephan.Claes@uz.kuleuven.be)
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Abstract

Background

Studies of hypothalamic–pituitary–adrenal (HPA) axis function in chronic fatigue syndrome (CFS) point to hypofunction, although there are negative reports. Suggested mechanisms include a reduced hypothalamic or supra-hypothalamic stimulus to the HPA axis and enhanced sensitivity to the negative feedback of glucocorticoids. The aim of the current study was to investigate HPA axis function in CFS with the dexamethasone/corticotropin-releasing factor (Dex/CRF) test, in analogy with research in affective disorders.

Method

Thirty-four well-characterized female CFS patients and 25 healthy control subjects participated in the low-dose Dex/CRF test. Current major depressive episode was an exclusion criterion. History of early-life stress (ELS) was assessed with the Structured Trauma Interview.

Results

Salivary cortisol responses after 0.5 mg Dex were lower in CFS patients than in controls (before 100 μg CRF, p=0.038; after 100 μg CRF, p=0.015). A secondary analysis revealed an influence of early-life stress and of oestrogen intake. After removal of the 10 participants who were taking an oral oestrogen, patients without a history of ELS showed lower cortisol responses than patients with ELS and controls (before CRF, p=0.005; after CRF, p=0.008).

Conclusions

CFS is globally associated with reduced cortisol responses in the combined low-dose Dex/CRF test, but this effect is only clearly present in CFS patients without a history of ELS. This study provides further support for an enhanced glucocorticoid negative feedback and/or a reduced central HPA axis drive in CFS. Furthermore, it demonstrates that ELS is an important variable to consider in CFS research.

Keywords

Child abusecortisolCRFsomatoform disorderstress
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 7 , July 2008 , pp. 963 - 973
Copyright
Copyright © 2007 Cambridge University Press

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References

Afari, N, Buchwald, D (2003). Chronic fatigue syndrome: a review. American Journal of Psychiatry 160, 221–236.Google Scholar
Altemus, M, Dale, JK, Michelson, D, Demitrack, MA, Gold, PW, Straus, SE (2001). Abnormalities in response to vasopressin infusion in chronic fatigue syndrome. Psychoneuroendocrinology 26, 175–188.Google Scholar
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association, Washington, DC.Google Scholar
Baghai, TC, Schule, C, Zwanzger, P, Minov, C, Holme, C, Padberg, F, Bidlingmaier, M, Strasburger, CJ, Rupprecht, R (2002). Evaluation of a salivary based combined dexamethasone/CRH test in patients with major depression. Psychoneuroendocrinology 27, 385–399.Google Scholar
Chapman, DP, Whitfield, CL, Felitti, VJ, Dube, SR, Edwards, VJ, Anda, RF (2004). Adverse childhood experiences and the risk of depressive disorders in adulthood. Journal of Affective Disorders 82, 217–225.CrossRefGoogle ScholarPubMed
Claes, SJ (2004). CRH, stress, and major depression: a psychobiological interplay. Vitamins and Hormones 69, 117–150.CrossRefGoogle ScholarPubMed
Cleare, AJ (2003). The neuroendocrinology of chronic fatigue syndrome. Endocrine Reviews 24, 236–252.Google Scholar
Cleare, AJ, Miell, J, Heap, E, Sookdeo, S, Young, L, Malhi, GS, O'Keane, V (2001). Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. Journal of Clinical Endocrinology and Metabolism 86, 3545–3554.Google Scholar
Cole, MA, Kim, PJ, Kalman, BA, Spencer, RL (2000). Dexamethasone suppression of corticosteroid secretion: evaluation of the site of action by receptor measures and functional studies. Psychoneuroendocrinology 25, 151–167.CrossRefGoogle ScholarPubMed
Coplan, JD, Andrews, MW, Rosenblum, LA, Owens, MJ, Friedman, S, Gorman, JM, Nemeroff, CB (1996). Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors: implications for the pathophysiology of mood and anxiety disorders. Proceedings of the National Academy of Sciences USA 93, 1619–1623.Google Scholar
Demitrack, MA, Crofford, LJ (1998). Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Annals of the New York Academy of Sciences 40, 684–697.CrossRefGoogle Scholar
Demitrack, MA, Dale, JK, Straus, SE, Laue, L, Listwak, SJ, Kruesi, MJ, Chrousos, GP, Gold, PW (1991). Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. Journal of Clinical Endocrinology and Metabolism 73, 1224–1234.Google Scholar
Draijer, N (1989). Gestructureerd Trauma Interview. Vakgroep Psychiatrie, Vrije Universiteit Amsterdam: Amsterdam.Google Scholar
Draijer, N, Langeland, W (1999). Childhood trauma and perceived parental dysfunction in the etiology of dissociative symptoms in psychiatric inpatients. American Journal of Psychiatry 156, 379–385.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1999). Structured Clinical Interview for DSM-IV Axis I Disorders. Version 2.0 (Dutch translation: M. A. C., van Groenestijn, G. W., Akkerhuis, R., W. Kupka, N., Schneider and W. A., Nolen, 1999). Swets & Zeitlinger BV: Lisse.Google Scholar
Fries, E, Hesse, J, Hellhammer, J, Hellhammer, DH (2005). A new view on hypocortisolism. Psychoneuroendocrinology 30, 1010–1016.Google Scholar
Fukuda, K, Straus, SE, Hickie, I, Sharpe, MC, Dobbins, JG, Komaroff, A (1994). The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Annals of Internal Medicine 121, 953–959.Google Scholar
Gaab, J, Huster, D, Peisen, R, Engert, V, Heitz, V, Schad, T, Schurmeyer, TH, Ehlert, U (2002 a). Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation. Psychosomatic Medicine 64, 951–962.Google Scholar
Gaab, J, Huster, D, Peisen, R, Engert, V, Heitz, V, Schad, T, Schurmeyer, TH, Ehlert, U (2003 b). Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects. Psychosomatics 44, 113–119.CrossRefGoogle ScholarPubMed
Gaab, J, Hustern, D, Peisen, R, Engert, V, Schad, T, Schurmeyer, TH, Ehlert, U (2002 b). Low-dose dexamethasone suppression test in chronic fatigue syndrome and health. Psychosomatic Medicine 64, 311–318.Google Scholar
Gaab, J, Rohleder, N, Heitz, V, Schad, T, Engert, V, Schürmeyer, TH, Ehlert, U (2003 a). Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome. Acta Neuropsychiatrica 15, 184–191.Google Scholar
Gerrity, TR, Papanicolaou, DA, Amsterdam, JD, Bingham, S, Grossman, A, Hedrick, T, Herberman, RB, Krueger, G, Levine, S, Mohagheghpour, N, Moore, RC, Oleske, J, Snell, CR, CFIDS Association of America Immunologic Aspects of Chronic Fatigue Syndrome (2004). Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health. Neuroimmunomodulation 11, 351–357.Google Scholar
Gold, PW, Chrousos, GP (2002). Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Molecular Psychiatry 7, 254–275.Google Scholar
Hardt, J, Rutter, M (2004). Validity of adult retrospective reports of adverse childhood experiences: review of the evidence. Journal of Child Psychology and Psychiatry 45, 260–273.Google Scholar
Heim, C, Ehlert, U, Hellhammer, DH (2000 a). The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 25, 1–35.CrossRefGoogle ScholarPubMed
Heim, C, Newport, DJ, Bonsall, R, Miller, AH, Nemeroff, CB (2001). Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. American Journal of Psychiatry 158, 575–581.CrossRefGoogle ScholarPubMed
Heim, C, Newport, DJ, Heit, S, Graham, YP, Wilcox, M, Bonsall, R, Miller, AH, Nemeroff, CB (2000 b). Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. Journal of the American Medical Association 284, 592–597.Google Scholar
Heim, C, Plotsky, PM, Nemeroff, CB (2004). Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology 29, 641–648.Google Scholar
Heim, C, Wagner, D, Maloney, E, Papanicolaou, DA, Solomon, L, Jones, JF, Unger, ER, Reeves, WC (2006). Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Archives of General Psychiatry 63, 1258–1266.Google Scholar
Heuser, IJ, Gotthardt, U, Schweiger, U, Schmider, J, Lammers, CH, Dettling, M, Holsboer, F (1994 b). Age-associated changes of pituitary-adrenocortical hormone regulation in humans: importance of gender. Neurobiology of Aging 15, 227–231.Google Scholar
Heuser, IJ, Yassouridis, A, Holsboer, F (1994 a). The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. Journal of Psychiatric Research 28, 341–356.Google Scholar
Holsboer, F (2000). The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23, 477–501.Google Scholar
Hudson, M, Cleare, AJ (1999). The 1microg short Synacthen test in chronic fatigue syndrome. Clinical Endocrinology 51, 625–630.Google Scholar
Inder, WJ, Prickett, TC, Mulder, RT (2005). Normal opioid tone and hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome despite marked functional impairment. Clinical Endocrinology 62, 343–348.CrossRefGoogle ScholarPubMed
Jason, LA, Richman, JA, Rademaker, AW, Jordan, KM, Plioplys, AV, Taylor, RR (1999). A community-based study of chronic fatigue syndrome. Archives of Internal Medicine 159, 2129–2137.Google Scholar
Jerjes, WK, Taylor, NF, Wood, PJ, Cleare, AJ (2007). Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome. Psychoneuroendocrinology 32, 192–198.Google Scholar
Kirschbaum, C, Hellhammer, DH (1994). Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology 19, 313–333.CrossRefGoogle ScholarPubMed
Kirschbaum, C, Kudielka, BM, Gaab, J, Schommer, NC, Hellhammer, DH (1999). Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosomatic Medicine 61, 154–162.Google Scholar
Künzel, HE, Binder, EB, Nickel, T, Ising, M, Fuchs, B, Majer, M, Pfennig, A, Ernst, G, Kern, N, Schmid, DA, Uhr, M, Holsboer, F, Modell, S (2003). Pharmacological and nonpharmacological factors influencing hypothalamic-pituitary-adrenocortical axis reactivity in acutely depressed psychiatric in-patients, measured by the Dex-CRH test. Neuropsychopharmacology 28, 2169–2178.Google Scholar
Ladd, CO, Owens, MJ, Nemeroff, CB (1996). Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology 137, 1212–1218.Google Scholar
McCauley, J, Kern, DE, Kolodner, K, Dill, L, Schroeder, AF, DeChant, HK, Ryden, J, Derogatis, LR, Bass, EB (1997). Clinical characteristics of women with a history of childhood abuse: unhealed wounds. Journal of the American Medical Association 277, 1362–1368.Google Scholar
Moorkens, G, Berwaerts, J, Wynants, H, Abs, R (2000). Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome. Clinical Endocrinology 53, 99–106.CrossRefGoogle ScholarPubMed
Newport, DJ, Heim, C, Bonsall, R, Miller, AH, Nemeroff, CB (2004). Pituitary-adrenal responses to standard and low-dose dexamethasone suppression tests in adult survivors of child abuse. Biological Psychiatry 55, 10–20.Google Scholar
Parker, AJ, Wessely, S, Cleare, AJ (2001). The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychological Medicine 31, 1331–1345.Google Scholar
Plotsky, PM, Meaney, MJ (1993). Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Research Molecular Brain Research 18, 195–200.Google Scholar
Plotsky, PM, Owens, MJ, Nemeroff, CB (1998). Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis. Psychiatric Clinics of North America 21, 293–307.Google Scholar
Pruessner, JC, Kirschbaum, C, Meinlschmid, G, Hellhammer, DH (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28, 916–931.Google Scholar
Rinne, T, de Kloet, ER, Wouters, L, Goekoop, JG, DeRijk, RH, van den Brink, W (2002). Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse. Biological Psychiatry 52, 1102–1112.Google Scholar
Rinne, T, Westenberg, HG, den Boer, JA, van den Brink, W (2000). Serotonergic blunting to meta-chlorophenylpiperazine (m-CPP) highly correlates with sustained childhood abuse in impulsive and autoaggressive female borderline patients. Biological Psychiatry 47, 548–556.Google Scholar
Roberts, AD, Wessely, S, Chalder, T, Papadopoulos, A, Cleare, AJ (2004). Salivary cortisol response to awakening in chronic fatigue syndrome. British Journal of Psychiatry 184, 136–141.Google Scholar
Scott, LV, Burnett, F, Medbak, S, Dinan, TG (1998 b). Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome. Psychological Medicine 28, 285–293.Google Scholar
Scott, LV, Medbak, S, Dinan, TG (1998 a). Blunted adrenocorticotropin and cortisol responses to corticotropin-releasing hormone stimulation in chronic fatigue syndrome. Acta Psychiatrica Scandinavica 97, 450–457.CrossRefGoogle ScholarPubMed
Scott, LV, Medbak, S, Dinan, TG (1998 c). The low dose ACTH test in chronic fatigue syndrome and in health. Clinical Endocrinology 48, 733–737.Google Scholar
Scott, LV, Medbak, S, Dinan, TG (1999). Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers. Biological Psychiatry 45, 1447–1454.CrossRefGoogle ScholarPubMed
Stein, MB, Yehuda, R, Koverola, C, Hanna, C (1997). Enhanced dexamethasone suppression of plasma cortisol in adult women traumatized by childhood sexual abuse. Biological Psychiatry 42, 680–686.Google Scholar
Van Den Eede, F, Moorkens, G, Van Houdenhove, B, Cosyns, P, Claes, SJ (2007). Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. Neuropsychobiology 55, 112–120.Google Scholar
Van Houdenhove, B, Egle, UT (2004). Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together. Psychotherapy and Psychosomatics 73, 267–275.CrossRefGoogle ScholarPubMed
Van Houdenhove, B, Neerinckx, E, Lysens, R, Vertommen, H, Van Houdenhove, L, Onghena, P, Westhovens, R, D'Hooghe, MB (2001). Victimization in chronic fatigue syndrome and fibromyalgia in tertiary care: a controlled study on prevalence and characteristics. Psychosomatics 42, 21–28.Google Scholar
Vercoulen, JHMM, Alberts, M, Bleijenberg, G (1999). De Checklist Individual Strength (CIS). Gedragstherapie 32, 131–136.Google Scholar
Visser, J, Blauw, B, Hinloopen, B, Brommer, E, de Kloet, ER, Kluft, C, Nagelkerken, L (1998). CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. Journal of Infectious Disorders 77, 451–454.Google Scholar
Visser, J, Graffelman, W, Blauw, B, Haspels, I, Lentjes, E, de Kloet, ER, Nagelkerken, L (2001 a). LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. Journal of Neuroimmunology 119, 343–349.Google Scholar
Visser, J, Lentjes, E, Haspels, I, Graffelman, W, Blauw, B, de Kloet, R, Nagelkerken, L (2001 b). Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of chronic fatigue syndrome patients, without evidence for altered density or affinity of glucocorticoid receptors. Journal of Investigative Medicine 49, 195–204.CrossRefGoogle ScholarPubMed
Widom, CS, Raphael, KG, DuMont, KA (2004). The case for prospective longitudinal studies in child maltreatment research: commentary on Dube, Williamson, Thompson, Felitti, and Anda. Child Abuse & Neglect 28, 715–722.Google Scholar
Yehuda, R, Halligan, SL, Golier, JA, Grossman, R, Bierer, LM (2004). Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder. Psychoneuroendocrinology 29, 389–404.Google Scholar
Yehuda, R, Southwick, SM, Krystal, JH, Bremner, D, Charney, DS, Mason, JW (1993). Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. American Journal of Psychiatry 150, 83–86.Google Scholar