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Salivary Cortisol Release and Hypothalamic Pituitary Adrenal Axis Feedback Sensitivity in Fibromyalgia Is Associated With Depression But Not With Pain

      Abstract

      Results on hypothalamicpituitary-adrenal (HPA) axis function in fibromyalgia are heterogeneous and studies that integrate psychological and biological mechanisms in the search for pathways to fibromyalgia are rare. The goal of the study was to evaluate cortisol release and HPA axis feedback regulation in fibromyalgia and its association with psychopathology and pain. Beneath assessment of pain thresholds and self-report of pain, salivary free cortisol release over the day before and after intake of 0.5 mg of dexamethasone was measured in 21 female patients with fibromyalgia and 26 control women. Depression was assessed by questionnaires and clinical interview. We found reduced feedback sensitivity and slightly enhanced cortisol release in patients with fibromyalgia compared with healthy control subjects. Post hoc analyses showed that these effects are exclusively found in those patients, who also had major depressive disorder. Patients with fibromyalgia had lower pain pressure threshold, whereas heat pain thresholds were comparable with control subjects. Pain pressure and heat pain thresholds were not associated with cortisol release. On the other hand measurements of affective pain experience and depression were positively correlated with salivary cortisol over the day. Our results support the hypotheses that HPA axis related alterations are associated with affective disturbances, for example, depression, in patients with fibromyalgia.

      Perspective

      The presented data suggest depression to be an important factor in HPA axis–related dysfunction in fibromyalgia. This might be one explanation for equivocal findings in the literature.

      Key words

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      References

        • Adler G.K.
        • Kinsley B.T.
        • Hurwitz S.
        • Mossey C.J.
        • Goldenberg D.L.
        Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome.
        Am J Med. 1999; 106: 534-543
        • Beck A.T.
        • Steer R.A.
        Beck-Depressions-Inventar: BDI.
        Testhandbuch, Bern: Huber1995
        • Calis M.
        • Gokce C.
        • Ates F.
        • Ulker S.
        • Izgi H.B.
        • Demir H.
        • Kirnap M.
        • Sofuoglu S.
        • Durak A.C.
        • Tutus A.
        • Kelestimur F.
        Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.
        J Endocrinol Invest. 2004; 27: 42-46
        • Carroll B.J.
        The dexamethasone suppression test for melancholia.
        Br J Psychiatry. 1982; 140: 292-304
        • Catley D.
        • Kaell A.T.
        • Kirschbaum C.
        • Stone A.A.
        A naturalistic evaluation of cortisol secretion in persons with fibromyalgia and rheumatoid arthritis.
        Arthritis Care Res. 2000; 13: 51-61
        • Crofford L.J.
        • Pillemer S.R.
        • Kalogeras K.T.
        • Cash J.M.
        • Michelson D.
        • Kling M.A.
        • Sternberg E.M.
        • Gold P.W.
        • Chrousos G.P.
        • Wilder R.L.
        Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia.
        Arthritis Rheum. 1994; 37: 1583-1592
        • Dadabhoy D.
        • Crofford L.J.
        • Spaeth M.
        • Russell I.J.
        • Clauw D.J.
        Biology and therapy of fibromyalgia: Evidence-based biomarkers for fibromyalgia syndrome.
        Arthritis Res Ther. 2008; 10: 211
      1. de Kloet C, Vermetten E, Lentjes E, Geuze E, van Pelt J, Manuel R, Heijnen C, Westenberg H. Differences in the response to the combined DEX-CRH test between PTSD patients with and without co-morbid depressive disorder. Psychoneuroendocrinology 33:313-320, 2008

        • Desmeules J.A.
        • Cedraschi C.
        • Rapiti E.
        • Baumgartner E.
        • Finckh A.
        • Cohen P.
        • Dayer P.
        • Vischer T.L.
        Neurophysiologic evidence for a central sensitization in patients with fibromyalgia.
        Arthritis Rheum. 2003; 48: 1420-1429
        • Ferraccioli G.
        • Cavalieri F.
        • Salaffi F.
        • Fontana S.
        • Scita F.
        • Nolli M.
        • Maestri D.
        Neuroendocrinologic findings in primary fibromyalgia (soft tissue chronic pain syndrome) and in other chronic rheumatic conditions (rheumatoid arthritis, low back pain).
        J Rheumatol. 1990; 17: 869-873
        • Geisser M.E.
        • Glass J.M.
        • Rajcevska L.D.
        • Clauw D.J.
        • Williams D.A.
        • Kileny P.R.
        • Gracely R.H.
        A psychophysical study of auditory and pressure sensitivity in patients with fibromyalgia and healthy controls.
        J Pain. 2008; 9: 417-422
        • Geissner E.
        Verarbeitung chronischer Schmerzen: Skalen zur Erfassung der Schmerzbewältigung und der schmerzbedingten psychischen Beeinträchtigung.
        Zeitschrift für Klinische Psychologie. 1999; 28: 280-290
        • Gold P.W.
        • Gabry K.E.
        • Yasuda M.R.
        • Chrousos G.P.
        Divergent endocrine abnormalities in melancholic and atypical depression: Clinical and pathophysiologic implications.
        Endocrinol Metab Clin North Am. 2002; 31: 37-62
        • Gracely R.H.
        • Petzke F.
        • Wolf J.M.
        • Clauw D.J.
        Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia.
        Arthritis Rheum. 2002; 46: 1333-1343
        • Griep E.N.
        • Boersma J.W.
        • de Kloet E.R.
        Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome.
        J Rheumatol. 1993; 20: 469-474
        • Griep E.N.
        • Boersma J.W.
        • Lentjes E.G.
        • Prins A.P.
        • van der Korst J.K.
        • de Kloet E.R.
        Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain.
        J Rheumatol. 1998; 25: 1374-1381
        • Gur A.
        • Cevik R.
        • Nas K.
        • Colpan L.
        • Sarac S.
        Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones.
        Arthritis Res Ther. 2004; 6: R232-R238
        • Gur A.
        • Cevik R.
        • Sarac A.J.
        • Colpan L.
        • Em S.
        Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary fibromyalgia: The potential roles of depression, fatigue, and sleep disturbance in the occurrence of hypocortisolism.
        Ann Rheum Dis. 2004; 63: 1504-1506
        • Kirnap M.
        • Colak R.
        • Eser C.
        • Ozsoy O.
        • Tutus A.
        • Kelestimur F.
        A comparison between low-dose (1 microg), standard-dose (250 microg) ACTH stimulation tests and insulin tolerance test in the evaluation of hypothalamo-pituitary-adrenal axis in primary fibromyalgia syndrome.
        Clin Endocrinol (Oxf). 2001; 55: 455-459
        • Klerman E.B.
        • Goldenberg D.L.
        • Brown E.N.
        • Maliszewski A.M.
        • Adler G.K.
        Circadian rhythms of women with fibromyalgia.
        J Clin Endocrinol Metab. 2001; 86: 1034-1039
        • Kraemer H.C.
        • Giese-Davis J.
        • Yutsis M.
        • O'Hara R.
        • Neri E.
        • Gallagher-Thompson D.
        • Taylor C.B.
        • Spiegel D.
        Design decisions to optimize reliability of daytime cortisol slopes in an older population.
        Am J Geriatr Psychiatry. 2006; 14: 325-333
        • Kudielka B.M.
        • Kirschbaum C.
        Sex differences in HPA axis responses to stress: A review.
        Biolog Psychol. 2005; 69: 113-132
        • Lautenbacher S.
        • Rollman G.B.
        Possible deficiencies of pain modulation in fibromyalgia.
        Clin J Pain. 1997; 13: 189-196
        • Lautenbacher S.
        • Rollman G.B.
        • McCain G.A.
        Multi-method assessment of experimental and clinical pain in patients with fibromyalgia.
        Pain. 1994; 59: 45-53
        • Lentjes E.G.
        • Griep E.N.
        • Boersma J.W.
        • Romijn F.P.
        • de Kloet E.R.
        Glucocorticoid receptors, fibromyalgia and low back pain.
        Psychoneuroendocrinology. 1997; 22: 603-614
        • Maes M.
        • Lin A.
        • Bonaccorso S.
        • van Hunsel F.
        • Van Gastel A.
        • Delmeire L.
        • Biondi M.
        • Bosmans E.
        • Kenis G.
        • Scharpe S.
        Increased 24-hour urinary cortisol excretion in patients with post-traumatic stress disorder and patients with major depression, but not in patients with fibromyalgia.
        Acta Psychiatr Scand. 1998; 98: 328-335
        • McCain G.A.
        • Tilbe K.S.
        Diurnal hormone variation in fibromyalgia syndrome: A comparison with rheumatoid arthritis.
        J Rheumatol Suppl. 1989; 19: 154-157
        • McLean S.A.
        • Williams D.A.
        • Harris R.E.
        • Kop W.J.
        • Groner K.H.
        • Ambrose K.
        • Lyden A.K.
        • Gracely R.H.
        • Crofford L.J.
        • Geisser M.E.
        • Sen A.
        • Biswas P.
        • Clauw D.J.
        Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia.
        Arthritis Rheum. 2005; 52: 3660-3669
      2. Musselmann DL, DeBattista C, Nathan KI, Kilts CD, Schatzberg AF, Nemeroff CB: Biology of mood disorders, in Schatzberg AF, Nemeroff CB (eds): Textbook of Psychopharmacology, (2nd ed.). Arlington, VA, American Psychiatry Publishing, Inc, 1998

        • 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. 2003; 28: 916-931
        • Riedel W.
        • Layka H.
        • Neeck G.
        Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones.
        Z Rheumatol. 1998; 57: 81-87
        • Sephton S.E.
        • Sapolsky R.M.
        • Kraemer H.C.
        • Spiegel D.
        Diurnal cortisol rhythm as a predictor of breast cancer survival.
        J Natl Cancer Inst. 2000; 92: 994-1000
        • Sherman J.J.
        • Turk D.C.
        • Okifuji A.
        Prevalence and impact of posttraumatic stress disorder-like symptoms on patients with fibromyalgia syndrome.
        Clin J Pain. 2000; 16: 127-134
      3. Smith BW, Tooley EM, Montague EQ, Robinson AE, Cosper CJ, Mullins PG. Habituation and sensitization to heat and cold pain in women with fibromyalgia and healthy controls. Pain 140:420-428, 2008

        • Staud R.
        • Bovee C.E.
        • Robinson M.E.
        • Price D.D.
        Cutaneous C-fiber pain abnormalities of fibromyalgia patients are specifically related to temporal summation.
        Pain. 2009; 139: 315-323
        • Staud R.
        • Spaeth M.
        Psychophysical and neurochemical abnormalities of pain processing in fibromyalgia.
        CNS Spectrums. 2008; 13: 12-17
        • Weissbecker I.
        • Floyd A.
        • Dedert E.
        • Salmon P.
        • Sephton S.
        Childhood trauma and diurnal cortisol disruption in fibromyalgia syndrome.
        Psychoneuroendocrinology. 2006; 31: 312-324
        • Williams D.A.
        • Gracely R.H.
        Biology and therapy of fibromyalgia: Functional magnetic resonance imaging findings in fibromyalgia.
        Arthritis Res Ther. 2006; 8: 224
        • Wingenfeld K.
        • Driessen M.
        • Adam B.
        • Hill A.
        Overnight urinary cortisol release in women with borderline personality disorder depends on comorbid PTSD and depressive psychopathology.
        Eur Psychiatry. 2007; 22: 309-312
        • Wingenfeld K.
        • Heim C.
        • Schmidt I.
        • Wagner D.
        • Meinlschmidt G.
        • Hellhammer D.H.
        HPA axis reactivity and lymphocyte glucocorticoid sensitivity in fibromyalgia syndrome and chronic pelvic pain.
        Psychosom Med. 2008; 70: 65-72
        • Wingenfeld K.
        • Hill A.
        • Adam B.
        • Driessen M.
        Dexamethasone suppression test in borderline personality disorder: Impact of PTSD symptoms.
        Psychiatry Clin Neurosci. 2007; 61: 681-683
        • Wingenfeld K.
        • Wagner D.
        • Schmidt I.
        • Meinlschmidt G.
        • Hellhammer D.H.
        • Heim C.
        The low-dose dexamethasone suppression test in fibromyalgia.
        J Psychosom Res. 2007; 62: 85-91
        • Wittchen H.U.
        • Zaudig M.
        • Fydrich T.
        Strukturiertes Klinisches Interview für DSM-IV. Achse I: Psychische Störungen. SKID-I.
        Hogrefe, Göttingen, Bern, Toronto, Seattle1997
        • Wolfe F.
        Fibromyalgia: The clinical syndrome.
        Rheum Dis Clin North Am. 1989; 15: 1-18
        • Wolfe F.
        • Ross K.
        • Anderson J.
        • Russell I.J.
        • Hebert L.
        The prevalence and characteristics of fibromyalgia in the general population.
        Arthritis Rheum. 1995; 38: 19-28
        • Wolfe F.
        • Smythe H.A.
        • Yunus M.B.
        • Bennett R.M.
        • Bombardier C.
        • Goldenberg D.L.
        • Tugwell P.
        • Campbell S.M.
        • Abeles M.
        • Clark P.
        • Fam A.G.
        • Farber S.J.
        • Fiechtner J.J.
        • Franklin C.M.
        • Gatter R.A.
        • Hamaty D.
        • Lessard J.
        • Lichtbroun A.S.
        • Masi A.T.
        • McCain G.
        • Reynolds W.J.
        • Romano T.J.
        • Russel I.J.
        • Sheon R.P.
        The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia: Report of the Multicenter Criteria Committee.
        Arthritis Rheum. 1990; 33: 160-172
        • Yehuda R.
        Current status of cortisol findings in post-traumatic stress disorder.
        Psychiatr Clin North Am. 2002; 25: 341-368
      4. Zerssen von D, Brähler E, Schumacher J, Strauß B. Die Beschwerde-Liste (BL). Göttingen: Hogrefe: 2002

      5. Zerssen von D, Koeller DM. Klinische Selbstbeurteilungngs-Skalen aus dem Psychiatrischen Informations-System (PSYCHIS München). Weinheim: 1976