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Brain-immune interactions and disease susceptibility

Molecular Psychiatry volume 10, pages 239–250 (2005)Cite this article

A Corrigendum to this article was published on 27 September 2005

Abstract

Many studies have established the routes by which the immune and central nervous (CNS) systems communicate. This network of connections permits the CNS to regulate the immune system through both neuroendocrine and neuronal pathways. In turn, the immune system signals the CNS through neuronal and humoral routes, via immune mediators and cytokines. This regulatory system between the immune system and CNS plays an important role in susceptibility and resistance to autoimmune, inflammatory, infectious and allergic diseases. This review focuses on the regulation of the immune system via the neuroendocrine system, and underlines the link between neuroendocrine dysregulation and development of major depressive disorders, autoimmune diseases and osteoporosis.

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References

  1. Webster JI, Tonelli L, Sternberg EM . Neuroendocrine regulation of immunity. Annu Rev Immunol 2002; 20: 125–163.

    Article  CAS  PubMed  Google Scholar 

  2. Cohen N, Kinney S . Exploring the phylogenetic history of neural-immune system interactions. In: Ader DCRF (ed). Psychoneuroimmunology, 2nd edn, Vol 2. San Diego, CA: Academic Press, 2001, p 856.

    Google Scholar 

  3. Dantzer R . Cytokines and sickness behavior. In: Kronfol Z (ed) Cytokines and Mental Health, 1st edn, Vol 1. Kluwer Academic Publishers: Ann Arbor, MI, 2003, p 425.

    Google Scholar 

  4. Miller AH, Pariante CM, Pearce BD . Effects of cytokines on glucocorticoid receptor expression and function. Glucocorticoid resistance and relevance to depression. Adv Exp Med Biol 1999; 461: 107–110.

    Article  CAS  PubMed  Google Scholar 

  5. Miller AH . Cytokines and sickness behavior: implications for cancer care and control. Brain Behav Immun 2003; 17(Suppl 1): S132–S134.

    Article  PubMed  Google Scholar 

  6. Maier SF, Watkins LR . Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998; 105: 83–107.

    Article  CAS  PubMed  Google Scholar 

  7. Licinio J, Wong ML . The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. Mol Psychiatry 1999; 4: 317–327.

    Article  CAS  PubMed  Google Scholar 

  8. Tracey KJ . The inflammatory reflex. Nature 2002; 420: 853–859.

    Article  CAS  PubMed  Google Scholar 

  9. Sanders VM, Kasprowicz DJ, Swanson-Mungerson MA, Podojil JR, Kohm AP . Adaptive immunity in mice lacking the beta(2)-adrenergic receptor. Brain Behav Immun 2003; 17: 55–67.

    Article  CAS  PubMed  Google Scholar 

  10. Green PG, Luo J, Heller PH, Levine JD . Further substantiation of a significant role for the sympathetic nervous system in inflammation. Neuroscience 1993; 55: 1037–1043.

    Article  CAS  PubMed  Google Scholar 

  11. Levine JD, Dardick SJ, Roizen MF, Helms C, Baubaum AI . Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis. J Neurosci 1986; 6: 3423–3429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Heijnen CJ, Kavelaars A . The importance of being receptive. J Neuroimmunol 1999; 100: 197–202.

    Article  CAS  PubMed  Google Scholar 

  13. Moynihan J, Kruszewska B, Madden K, Callahan T . Sympathetic nervous system regulation of immunity. J Neuroimmunol 2004; 147: 87–90.

    Article  CAS  PubMed  Google Scholar 

  14. Bulloch K, McEwen BS, Nordbery J, Diwa A, Baird S . Selective regulation of T-cell development and function by calcitonin gene-related peptide in thymus and spleen. An example of differential regional regulation of immunity by the neuroendocrine system. Ann NY Acad Sci 1998; 840: 551–562.

    Article  CAS  PubMed  Google Scholar 

  15. Ferreira S, Sachs D, Cunha F, Lorenzetti B . Persistent hyperalgesia and cytokines. In: Saade N, Apkarian A, Jabbur S (eds) Pain and Neuroimmune Interactions, Vol 1. Kluwer Academic/Plenum Publishers: Boston, USA, 1999, p 244.

    Google Scholar 

  16. Grimm MC, Newman R, Hassim Z, Cuan N, Connor SJ, Le Y et al. Cutting edge: vasoactive intestinal peptide acts as a potent suppressor of inflammation in vivo by trans-deactivating chemokine receptors. J Immunol 2003; 171: 4990–4994.

    Article  CAS  PubMed  Google Scholar 

  17. Rogers TJ, Steele AD, Howard OM, Oppenheim JJ . Bidirectional heterologous desensitization of opioid and chemokine receptors. Ann NY Acad Sci 2000; 917: 19–28.

    Article  CAS  PubMed  Google Scholar 

  18. Pedotti R, DeVoss JJ, Youssef S, Mitchell D, Wedemeyer J, Madanat R et al. Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination. Proc Natl Acad Sci USA 2003; 100: 1867–1872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Steinman L . Elaborate interactions between the immune and nervous systems. Nat Immunol 2004; 5: 575–581.

    Article  CAS  PubMed  Google Scholar 

  20. Adcock IM, Ito K . Molecular mechanisms of corticosteroid actions. Monaldi Arch Chest Dis 2000; 55: 256–266.

    CAS  PubMed  Google Scholar 

  21. Barnes PJ . Anti-inflammatory actions of glucocorticoids: molecular mechansims. Clin Sci 1998; 94: 557–572.

    Article  CAS  Google Scholar 

  22. Nuclear Receptor Nomenclature Committee. A unified nomenclature system for the nuclear receptor superfamily. Cell 1999; 97: 161–163.

  23. Dhabhar FS, McEwen BS . Enhancing versus suppressive effects of stress hormones on skin immune function. Proc Natl Acad Sci USA 1999; 96: 1059–1064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Eskandari F, Webster JI, Sternberg EM . Neural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther 2003; 5: 251–265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Webster JI, Tonelli L, Sternberg EM . Neural immune interactions in inflammatory/autoimmune disease. In: Antel J (ed) Clinical Neuroimmunology. Oxford University Press: Oxford, 2004, in press.

    Google Scholar 

  26. DeRijk R, Michelson D, Karp B, Petrides J, Galliven H, Deuster P et al. Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) production in humans: high sensitivity of TNF alpha and resistance of IL-6. J Clin Endocrinol Metab 1997; 82: 2182–2191.

    CAS  PubMed  Google Scholar 

  27. Adcock IM . Molecular mechanisms of glucocorticosteroid actions. Pulmonary Pharmacol Ther 2000; 13: 115–126.

    Article  CAS  Google Scholar 

  28. Fauci AS . Immunosuppressive and anti-inflammatory effects of glucocorticoids. Monogr Endocrinol 1979; 12: 449–465.

    Article  CAS  PubMed  Google Scholar 

  29. Marx J . How the glucocorticoids suppress immunity. Science 1995; 270: 232–233.

    Article  CAS  PubMed  Google Scholar 

  30. Wilckens T . Glucocorticoids and immune function: physiological relevance and pathogenic potential of hormonal dysfunction. Trends Pharmacol Sci 1995; 16: 193–197.

    Article  CAS  PubMed  Google Scholar 

  31. Levo Y, Harbeck RJ, Kirkpatrick CH . Regulatory effect of hydrocortisone on the in vitro synthesis of IgE by human lymphocytes. Int Arch Allergy Appl Immunol 1985; 77: 413–415.

    Article  CAS  PubMed  Google Scholar 

  32. Whitfield JF, MacManus JP, Gillan DJ . The possible mediation by cyclic AMP of the stimulation of thymocyte proliferation by vasopressin and the inhibition of this mitogenic action by thyrocalcitonin. J Cell Physiol 1970; 76: 65–76.

    Article  CAS  PubMed  Google Scholar 

  33. Wiegers GJ, Reul JM, Holsboer F, de Kloet ER . Enhancement of rat splenic lymphocyte mitogenesis after short term preexposure to corticosteroids in vitro. Endocrinology 1994; 135: 2351–2357.

    Article  CAS  PubMed  Google Scholar 

  34. Forner MA, Barriga C, Rodriguez AB, Ortega E . A study of the role of corticosterone as a mediator in exercise-induced stimulation of murine macrophage phagocytosis. J Physiol 1995; 488: 789–794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wiegers G, Reul J . Induction of cytokine receptors by glucocorticoids: functional and pathological significance. Trends Pharmacol Sci 1998; 19: 317–321.

    Article  CAS  PubMed  Google Scholar 

  36. Wang HC, Klein JR . Immune function of thyroid stimulating hormone and receptor. Crit Rev Immunol 2001; 21: 323–337.

    Article  PubMed  Google Scholar 

  37. Pawlikowski M, Stepien H, Komorowski J . Hypothalamic-pituitary-thyroid axis and the immune system. Neuroimmunomodulation 1994; 1: 149–152.

    Article  CAS  PubMed  Google Scholar 

  38. Kruger TE . Immunomodulation of peripheral lymphocytes by hormones of the hypothalamus-pituitary-thyroid axis. Adv Neuroimmunol 1996; 6: 387–395.

    Article  CAS  PubMed  Google Scholar 

  39. Kamilaris TC, DeBold CR, Johnson EO, Mamalaki E, Listwak SJ, Calogero AE et al. Effects of short and long duration hypothyroidism and hyperthyroidism on the plasma adrenocorticotropin and corticosterone responses to ovine corticotropin-releasing hormone in rats. Endocrinology 1991; 128: 2567–2576.

    Article  CAS  PubMed  Google Scholar 

  40. Cutolo M . The roles of steroid hormones in arthritis. Br J Rheumatol 1998; 37: 597–599.

    Article  CAS  PubMed  Google Scholar 

  41. Cutolo M, Wilder RL . Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases. Rheum Dis Clin N Am 2000; 26: 825–839.

    Article  CAS  Google Scholar 

  42. Cutolo M, Sulli A, Pizzorni C, Craviotto C, Straub RH et al. Hypothalamic-pituitary-adrenocortical and gonadal functions in rheumatoid arthritis. Ann NY Acad Sci 2003; 992: 107–117.

    Article  CAS  PubMed  Google Scholar 

  43. Olsen NJ, Kovacs WJ . Gonadal steroids and immunity. Endocr Rev 1996; 17: 369–384.

    CAS  PubMed  Google Scholar 

  44. Haller C, Holzner B, Mur E, Gunther V . The impact of life events on patients with rheumatoid arthritis: a psychological myth? Clin Exp Rheumatol 1997; 15: 175–179.

    CAS  PubMed  Google Scholar 

  45. Cutolo M, Foppiani L, Prete C, Ballarino P, Sulli A, Villaggio B et al. Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocorticoids. J Rheumatol 1999; 26: 282–288.

    CAS  PubMed  Google Scholar 

  46. Wolkowitz O, Reus V . Dehydroepiandrosterone in psychoneuroendocrinology. In: Wolkowitz O, Rothschild A (eds), Psychoneuroendocrinology, Vol 1, 1st edn. American Psychiatric Publishing, Inc.: Washington, DC, 2003, p 588.

    Google Scholar 

  47. Flood JF, Roberts E . Dehydroepiandrosterone sulfate improves memory in aging mice. Brain Res 1988; 448: 178–181.

    Article  CAS  PubMed  Google Scholar 

  48. Reddy DS, Kaur G, Kulkarni SK . Sigma (sigma1) receptor mediated anti-depressant-like effects of neurosteroids in the Porsolt forced swim test. Neuroreport 1998; 9: 3069–3073.

    Article  CAS  PubMed  Google Scholar 

  49. Melchior CL, Ritzmann RF . Dehydroepiandrosterone is an anxiolytic in mice on the plus maze. Pharmacol Biochem Behav 1994; 47: 437–441.

    Article  CAS  PubMed  Google Scholar 

  50. Bologa L, Sharma J, Roberts E . Dehydroepiandrosterone and its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures. J Neurosci Res 1987; 17: 225–234.

    Article  CAS  PubMed  Google Scholar 

  51. Del Cerro S, Garcia-Estrada J, Garcia-Segura LM . Neuroactive steroids regulate astroglia morphology in hippocampal cultures from adult rats. Glia 1995; 14: 65–71.

    Article  CAS  PubMed  Google Scholar 

  52. Guazzo EP, Kirkpatrick PJ, Goodyer IM, Shiers HM, Herbert J . Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age. J Clin Endocrinol Metab 1996; 81: 3951–3960.

    CAS  PubMed  Google Scholar 

  53. Wolkowitz OM, Reul JM . DHEA as a neurohormone in the treatment of depression and dementia. In: Mischoulon D, Rosenbaum J (eds). Natural Medications for Psychiatric Disorders. Lippincott Willians &Wilkins: New York, 2001; 62–82.

    Google Scholar 

  54. Medina KL, Strasser A, Kincade PW . Estrogen influences the differentiation, proliferation, and survival of early B-lineage precursors. Blood 2000; 95: 2059–2067.

    CAS  PubMed  Google Scholar 

  55. Kincade PW, Medina KL, Payne KJ, Rossi MI, Tudor KS, Yamashita Y et al. Early B-lymphocyte precursors and their regulation by sex steroids. Immunol Rev 2000; 175: 128–137.

    Article  CAS  PubMed  Google Scholar 

  56. Erlandsson MC, Ohlsson C, Gustafsson JA, Carlsten H . Role of oestrogen receptors alpha and beta in immune organ development and in oestrogen-mediated effects on thymus. Immunology 2001; 103: 17–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tsigos C, Chrousos GP . Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res 2002; 53: 865–871.

    Article  PubMed  Google Scholar 

  58. Petraglia F, Sutton S, Vale W, Plotsky P . Corticotropin-releasing factor decreases plasma luteinizing hormone levels in female rats by inhibiting gonadotropin-releasing hormone release into hypophysial-portal circulation. Endocrinology 1987; 120: 1083–1088.

    Article  CAS  PubMed  Google Scholar 

  59. Rivier C, Rivier J, Vale W . Stress-induced inhibition of reproductive functions: role of endogenous corticotropin-releasing factor. Science 1986; 231: 607–609.

    Article  CAS  PubMed  Google Scholar 

  60. Bonavera JJ, Kalra SP, Kalra PS . Mode of action of interleukin-1 in suppression of pituitary LH release in castrated male rats. Brain Res 1993; 612: 1–8.

    Article  CAS  PubMed  Google Scholar 

  61. Carroll BJ, Curtis GC, Davies BM, Mendels J, Sugerman AA . Urinary free cortisol excretion in depression. Psychol Med 1976a; 6: 43–50.

    Article  CAS  PubMed  Google Scholar 

  62. Carroll BJ, Curtis GC, Mendels J . Neuroendocrine regulation in depression. I. Limbic system-adrenocortical dysfunction. Arch Gen Psychiatry 1976b; 33: 1039–1044.

    Article  CAS  PubMed  Google Scholar 

  63. Brown WA, Shuey I . Response to dexamethasone and subtype of depression. Arch Gen Psychiatry 1980; 37: 747–751.

    Article  CAS  PubMed  Google Scholar 

  64. Mortola JF, Liu JH, Gillin JC, Rasmussen DD, Yen SS . Pulsatile rhythms of adrenocorticotropin (ACTH) and cortisol in women with endogenous depression: evidence for increased ACTH pulse frequency. J Clin Endocrinol Metab 1987; 65: 962–968.

    Article  CAS  PubMed  Google Scholar 

  65. Linkowski P, Van Cauter E, Leclercq R, Desmedt D, Brasseur M, Golstein J et al. ACTH, cortisol and growth hormone 24-hour profiles in major depressive illness. Acta Psychiatr Belg 1985; 85: 615–623.

    CAS  PubMed  Google Scholar 

  66. Rubin RT, Poland RE, Lesser IM, Martin DJ . Neuroendocrine aspects of primary endogenous depression. V. Serum prolactin measures in patients and matched control subjects. Biol Psychiatry 1989; 25: 4–21.

    Article  CAS  PubMed  Google Scholar 

  67. Yehuda R, Teicher MH, Trestman RL, Levengood RA, Siever LJ . Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis. Biol Psychiatry 1996; 40: 79–88.

    Article  CAS  PubMed  Google Scholar 

  68. Sachar EJ, IIellman L, Fukushima DK, Gallagher TF . Cortisol production in depressive illness. A clinical and biochemical clarification. Arch Gen Psychiatry 1970; 23: 289–298.

    Article  CAS  PubMed  Google Scholar 

  69. Maes M, Maes L, Suy E . Symptom profiles of biological markers in depression: a multivariate study. Psychoneuroendocrinology 1990; 15: 29–37.

    Article  CAS  PubMed  Google Scholar 

  70. Holsboer F . The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000; 23: 477–501.

    Article  CAS  PubMed  Google Scholar 

  71. Deuschle M, Schweiger U, Weber B, Gotthardt U, Korner A, Schmider J et al. Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls. J Clin Endocrinol Metab 1997; 82: 234–238.

    Article  CAS  PubMed  Google Scholar 

  72. Halbreich U, Asnis GM, Shindledecker R, Zumoff B, Nathan RS . Cortisol secretion in endogenous depression. I. Basal plasma levels. Arch Gen Psychiatry 1985a; 42: 904–908.

    Article  CAS  PubMed  Google Scholar 

  73. Halbreich U, Asnis GM, Shindledecker R, Zumoff B, Nathan RS . Cortisol secretion in endogenous depression. II. Time-related functions. Arch Gen Psychiatry 1985b; 42: 909–914.

    Article  CAS  PubMed  Google Scholar 

  74. Pfohl B, Sherman B, Schlechte J, Stone R . Pituitary–adrenal axis rhythm disturbances in psychiatric depression. Arch Gen Psychiatry 1985; 42: 897–903.

    Article  CAS  PubMed  Google Scholar 

  75. Posener JA, DeBattista C, Williams GH, Chmura Kraemer H, Kalehzan BM, Schatzberg AF . 24-Hour monitoring of cortisol and corticotropin secretion in psychotic and nonpsychotic major depression. Arch Gen Psychiatry 2000; 57: 755–760.

    Article  CAS  PubMed  Google Scholar 

  76. Nemeroff CB, Widerlov E, Bissette G, Walleus H, Karlsson I, Eklund K et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984; 226: 1342–1344.

    Article  CAS  PubMed  Google Scholar 

  77. Arato M, Banki CM, Nemeroff CB, Bissette G . Hypothalamic-pituitary-adrenal axis and suicide. Ann NY Acad Sci 1986; 487: 263–270.

    Article  CAS  PubMed  Google Scholar 

  78. Banki CM, Bissette G, Arato M, O'Connor L, Nemeroff CB . CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. Am J Psychiatry 1987; 144: 873–877.

    Article  CAS  PubMed  Google Scholar 

  79. Banki CM, Karmacsi L, Bissette G, Nemeroff CB . CSF corticotropin-releasing hormone and somatostatin in major depression: response to antidepressant treatment and relapse. Eur Neuropsychopharmacol 1992; 2: 107–113.

    Article  CAS  PubMed  Google Scholar 

  80. Krishnan KR, Doraiswamy PM, Lurie SN, Figiel GS, Husain MM, Boyko OB et al. Pituitary size in depression. J Clin Endocrinol Metab 1991; 72: 256–259.

    Article  CAS  PubMed  Google Scholar 

  81. Axelson DA, Doraiswamy PM, Boyko OB, Rodrigo Escalona P, McDonald WM, Ritchie JC et al. In vivo assessment of pituitary volume with magnetic resonance imaging and systematic stereology: relationship to dexamethasone suppression test results in patients. Psychiatry Res 1992; 44: 63–70.

    Article  CAS  PubMed  Google Scholar 

  82. Amsterdam JD, Marinelli DL, Arger P, Winokur A . Assessment of adrenal gland volume by computed tomography in depressed patients and healthy volunteers: a pilot study. Psychiatry Res 1987; 21: 189–197.

    Article  CAS  PubMed  Google Scholar 

  83. Nemeroff CB, Kiishnan KR, Reed D, Leder R, Beam C, Dunnick NR . Adrenal gland enlargement in major depression. A computed tomographic study. Arch Gen Psychiatry 1992; 49: 384–387.

    Article  CAS  PubMed  Google Scholar 

  84. Rubin RT, Phillips JJ, Sadow TF, McCracken JT . Adrenal gland volume in major depression. Increase during the depressive episode and decrease with successful treatment. Arch Gen Psychiatry 1995; 52: 213–218.

    Article  CAS  PubMed  Google Scholar 

  85. Raadsheer FC, Hoogendijk WJ, Stam FC, Tilders FJ, Swaab DF . Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994; 60: 436–444.

    Article  CAS  PubMed  Google Scholar 

  86. Raadsheer FC, van IIeerikhuize JJ, Lucassen PJ, Hoogendijk WJ, Tilders FJ, Swaab DF . Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression. Am J Psychiatry 1995; 152: 1372–1376.

    Article  CAS  PubMed  Google Scholar 

  87. Nemeroff CB . The role of corticotropin-releasing factor in the pathogenesis of major depression. Pharmacopsychiatry 1988; 21: 76–82.

    Article  CAS  PubMed  Google Scholar 

  88. Holsboer-Trachsler E, Stohler R, Hatzinger M . Repeated administration of the combined dexamethasone-human corticotropin releasing hormone stimulation test during treatment of depression. Psychiatry Res 1991; 38: 163–171.

    Article  CAS  PubMed  Google Scholar 

  89. Holsboer F, Von Bardeleben U . Serotonin reuptake inhibitors and DST status. Am J Psychiatry 1987; 144: 263–264.

    Article  CAS  PubMed  Google Scholar 

  90. Heuser I, Bissette G, Dettling M, Schweiger U, Gotthardt U, Schmidcr J et al. Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment. Depress Anxiety 1998; 8: 71–79.

    Article  CAS  PubMed  Google Scholar 

  91. De Bellis MD, Gold PW, Geracioti Jr TD, Listwak SJ, Kling MA . Association of fluoxetine treatment with reductions in CSF concentrations of corticotropin-releasing hormone and arginine vasopressin in patients with major depression. Am J Psychiatry 1993; 150: 656–657.

    Article  CAS  PubMed  Google Scholar 

  92. Nemeroff CB, Bissette G, Akil H, Fink M . Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy. Corticotrophin-releasing factor, beta-endorphin and somatostatin. Br J Psychiatry 1991; 158: 59–63.

    Article  CAS  PubMed  Google Scholar 

  93. Amsterdam JD, Maislin G, Winokur A, Berwish N, Kling M, Gold P . The oCRH stimulation test before and after clinical recovery from depression. J Affect Disord 1988; 14: 213–222.

    Article  CAS  PubMed  Google Scholar 

  94. Holsboer F, Spengler D, Heuser I . The role of corticotropin-releasing hormone in the pathogenesis of Cushing's disease, anorexia nervosa, alcoholism, affective disorders and dementia. Prog Brain Res 1992; 93: 385–417.

    Article  CAS  PubMed  Google Scholar 

  95. Fava GA, Fabbri S, Sonino N . Residual symptoms in depression: an emerging therapeutic target. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 1019–1027.

    Article  PubMed  Google Scholar 

  96. Nelson JC, Davis JM . DST studies in psychotic depression: a meta-analysis. Am J Psychiatry 1997; 154: 1497–1503.

    Article  CAS  PubMed  Google Scholar 

  97. Rush AJ, Giles DE, Schlesser MA, Orsulak PJ, Parker Jr CR, Weissenburger JE et al. The dexamethasone suppression test in patients with mood disorders. J Clin Psychiatry 1996; 57: 470–484.

    Article  CAS  PubMed  Google Scholar 

  98. Watson S, Gallagher P, Del-Estal D, Hearn A, Ferrier IN, Young AH . Hypothalamic-pituitary-adrenal axis function in patients with chronic depression. Psychol Med 2002; 32: 1021–1028.

    Article  CAS  PubMed  Google Scholar 

  99. van Praag HM . Faulty cortisol/serotonin interplay. Psychopathological and biological characterisation of a new, hypothetical depression subtype (SeCA depression). Psychiatry Res 1996; 65: 143–157.

    Article  CAS  PubMed  Google Scholar 

  100. Rybakowski JK, Twardowska K . The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness. J Psychiatr Res 1999; 33: 363–370.

    Article  CAS  PubMed  Google Scholar 

  101. Kumar A, Alcser K, Grunhaus L, Greden JF . Relationships of the dexamethasone suppression test to clinical severity and degree of melancholia. Biol Psychiatry 1986; 21: 436–444.

    Article  CAS  PubMed  Google Scholar 

  102. Lenox RH, Peyser JM, Rothschild B, Shipley J, Weaver L . Failure to normalize the dexamethasone suppression test: association with length of illness. Biol Psychiatry 1985; 20: 333–337.

    Article  CAS  PubMed  Google Scholar 

  103. Peeters F, Nicolson NA, Berkhof J . Levels and variability of daily life cortisol secretion in major depression. Psychiatry Res 2004; 126: 1–13.

    Article  CAS  PubMed  Google Scholar 

  104. Strickland PL, Deakin JF, Percival C, Dixon J, Gater RA, Goldberg DP . Bio-social origins of depression in the community. Interactions between social adversity, cortisol and serotonin neurotransmission. Br J Psychiatry 2002; 180: 168–173.

    Article  PubMed  Google Scholar 

  105. Scott LV, Salahuddin F, Cooney J, Svec F, Dinan TG . Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. J Affect Disord 1999; 54: 129–137.

    Article  CAS  PubMed  Google Scholar 

  106. Maes M, Calabrese J, Meltzer HY . The relevance of the in- vs outpatient status for studies on HPA-axis in depression: spontaneous hypercortisolism is a feature of major depressed inpatients and not of major depression per se. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18: 503–517.

    Article  CAS  PubMed  Google Scholar 

  107. Pariante CM, Miller AH . Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol Psychiatry 2001; 49: 391–404.

    Article  CAS  PubMed  Google Scholar 

  108. Owens MJ, Nemeroff CB . The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies. Ciba Found Symp 1993; 172: 296–308, discussion 308–316.

    CAS  PubMed  Google Scholar 

  109. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M . Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998; 19: 269–301.

    CAS  PubMed  Google Scholar 

  110. Juruena MF, Cleare AJ, Pariante CM . The hypothalamic pituitary adrenal axis, glucocroticoid receptor function and relevance to depression. Office J Braz Assoc 2004; 26: 180–188.

    Google Scholar 

  111. Yehuda R, Boisoneau D, Mason JW, Giller EL . Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders. Biol Psychiatry 1993; 34: 18–25.

    Article  CAS  PubMed  Google Scholar 

  112. Wassef AA, O'Boyle M, Gardner R, Rose RM, Brown A, Harris A et al. Glucocorticoid receptor binding in three different cell types in major depressive disorder: lack of evidence of receptor binding defect. Prog Neuropsychopharmacol Biol Psychiatry 1992; 16: 65–78.

    Article  CAS  PubMed  Google Scholar 

  113. Maguire TM, Thakore J, Dinan TG, Hopwood S, Breen KC . Plasma sialyltransferase levels in psychiatric disorders as a possible indicator of HPA axis function. Biol Psychiatry 1997; 41: 1131–1136.

    Article  CAS  PubMed  Google Scholar 

  114. Juruena MF, Cleare AJ, Bauer ME, Pariante CM . Molecular mechanism of GR sensitivity and relevant of affective disorders. Acta Neuropsychiatrica 2003; 15: 354–367.

    Article  PubMed  Google Scholar 

  115. Bauer ME, Papadopoulos A, Poon L, Perks P, Lightman SL, Checkley S, Shanks N . Altered glucocorticoid immunoregulation in treatment resistant depression. Psychoneuroendocrinology 2003; 28: 49–65.

    Article  CAS  PubMed  Google Scholar 

  116. Cotter PA, Mulligan OF, Landau S, Papadopoulos A, Lightman SL, Checkley SA . Vasoconstrictor response to topical beclomethasone in major depression. Psychoneuroendocrinology 2002; 27: 475–487.

    Article  CAS  PubMed  Google Scholar 

  117. Pariante CM, Pearce BD, Pisell TL, Sanchez CI, Po C, Su C, Miller AH . The proinflammatory cytokine, interleukin-1alpha, reduces glucocorticoid receptor translocation and function. Endocrinology 1999; 140: 4359–4366.

    Article  CAS  PubMed  Google Scholar 

  118. Rangarajan PN, Umesono K, Evans RM . Modulation of glucocorticoid receptor function by protein kinase A. Mol Endocrinol 1992; 6: 1451–1457.

    CAS  PubMed  Google Scholar 

  119. de Castro M, Elliot S, Kino T, Bamberger C, Karl M, Webster F, Chrousos GP . The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGR beta): tissue levels, mechanism of action, and potential physiologic role. Mol Med 1996; 2: 597–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Bronnegard M, Stierna P, Marcus C . Glucocorticoid resistant syndromes—molecular basis and clinical presentations. J Neuroendocrinol 1996; 8: 405–415.

    Article  CAS  PubMed  Google Scholar 

  121. Fraser SA, Kroenke K, Callahan CM, Hui SL, Williams Jr JW, Unutzer J . Low yield of thyroid-stimulating hormone testing in elderly patients with depression. Gen Hosp Psychiatry 2004; 26: 302–309.

    Article  PubMed  Google Scholar 

  122. Boswell EB, Anfinson TH, Nemeroff CB . Depression associated with endocrine disorder. In: Robertson MM, Katona CLE (eds). Depression and Physical Illness. Wiley: Chichester, England, 1997; 256–292.

    Google Scholar 

  123. Cleare AJ, McGregor A, O'Keane V . Neuroendocrine evidence for an association between hypothyroidism, reduced central 5-HT activity and depression. Clin Endocrinol (Oxford) 1995; 43: 713–719.

    Article  CAS  Google Scholar 

  124. Bahls SC, de Carvalho GA . The relation between thyroid function and depression: a review. Rev Bras Psiquiatr 2004; 26: 41–49.

    Article  PubMed  Google Scholar 

  125. Fava M, Labbate LA, Abraham ME, Rosenbaum JF . Hypothyroidism and hyperthyroidism in major depression revisited. J Clin Psychiatry 1995; 56: 186–192.

    CAS  PubMed  Google Scholar 

  126. Maes M, Meltzer HY, Cosyns P, Suy E, Schotte C . An evaluation of basal hypothalamic-pituitary-thyroid axis function in depression: results of a large-scaled and controlled study. Psychoneuroendocrinology 1993; 18: 607–620.

    Article  CAS  PubMed  Google Scholar 

  127. Baumgartner A, Graf KJ, Kurten I, Meinhold H . The hypothalamic-pituitary-thyroid axis in psychiatric patients and healthy subjects: Parts 1–4. Psychiatry Res 1988; 24: 271–332.

    Article  CAS  PubMed  Google Scholar 

  128. O'Connor D, Gwirtsman H, Lossen P . Thyroid function in psychiatry disorders. In: Wolkowitz O, RothschildA (eds). Psychoneuroendocrinology, Vol 1. American Psychiatric Publishing: London, England, 2003, p 588.

    Google Scholar 

  129. Briggs J, McBrigc L, Hagino O . Screening depressives for causative medical illness; the example of thyroid testing, II: hypothesis testing in ambulatory depressives. Depression 1993; 1: 220–224.

    Article  Google Scholar 

  130. Kirkegaard C, Faber J . Altered serum levels of thyroxine, triiodothyronines and diiodothyronines in endogenous depression. Acta Endocrinol (Copenh) 1981; 96: 199–207.

    Article  CAS  Google Scholar 

  131. Loosen PT . Hormones of the hypothalamic-pituitary-thyroid axis: a psychoneuroendocrine perspective. Pharmacopsychiatry 1986; 19: 401–415.

    Article  CAS  PubMed  Google Scholar 

  132. Loosen PT . Thyroid function in affective disorders and alcoholism. Endocrinol Metab Clin N Am 1988; 17: 55–82.

    Article  CAS  Google Scholar 

  133. Vandoolaeghe E, Maes M, Vandevyvere J, Neels H . Hypothalamic-pituitary-thyroid-axis function in treatment resistant depression. J Affect Disord 1997; 43: 143–150.

    Article  CAS  PubMed  Google Scholar 

  134. Ordas DM, Labbate LA . Routine screening of thyroid function in patients hospitalized for major depression or dysthymia? Ann Clin Psychiatry 1995; 7: 161–165.

    Article  CAS  PubMed  Google Scholar 

  135. Gendall KA, Joyce PR, Mulder RT, Luty SE . Thyroid indices and response to fluoxetine and nortriptyline in major depression. J Psychopharmacol 2003; 17: 431–437.

    Article  CAS  PubMed  Google Scholar 

  136. Sarandol A, Taneli B, Sivrioglu Y . Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axis findings in depressive disorder. Turk Psikiyatri Derg 2003; 14: 116–124.

    PubMed  Google Scholar 

  137. Staner L, Duval F, Haba J, Mokrani MC, Macher JP . Disturbances in hypothalamo pituitary adrenal and thyroid axis identify different sleep EEG patterns in major depressed patients. J Psychiatr Res 2003; 37: 1–8.

    Article  CAS  PubMed  Google Scholar 

  138. Fountoulakis KN, Iacovides A, Grammaticos P, St Kaprinis G, Bech P . Thyroid function in clinical subtypes of major depression: an exploratory study. BMC Psychiatry 2004; 4: 6.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Carta MG, Loviseili A, Hardoy MC, Massa S, Cadeddu M, Sardu C et al. The link between thyroid autoimmunity (antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future. BMC Psychiatry 2004; 4: 25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Luo LG, Bruhn T, Jackson IM . Glucocorticoids stimulate thyrotropin-releasing hormone gene expression in cultured hypothalamic neurons. Endocrinology 1995; 136: 4945–4950.

    Article  CAS  PubMed  Google Scholar 

  141. Kirkegaard C, Faber J . The role of thyroid hormones in depression. Eur J Endocrinol 1998; 138: 1–9.

    Article  CAS  PubMed  Google Scholar 

  142. Altshuler LL, Bauer M, Frye MA, Gitlin MJ, Mintz J, Szuba MP et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry 2001; 158: 1617–1622.

    Article  CAS  PubMed  Google Scholar 

  143. Wick G, Sgonc R, Lechner O . Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases. Ann NY Acad Sci 1998; 840: 591–598.

    Article  CAS  PubMed  Google Scholar 

  144. Lechner O, Hu Y, Jafarian Tehrani M, Dietrich H, Schwartz S, Herold M et al. Disturbed immunoendocine communication via the hypothalamo-pituitaty-adrenal axis in murine lupus. Brain Behav Immun 1996; 10: 337–350.

    Article  CAS  PubMed  Google Scholar 

  145. Hu Y, Dietrich H, Herold M, Heinrich PC, Wick G . Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. Int Arch Allergy Immunol 1993; 102: 232–241.

    Article  CAS  PubMed  Google Scholar 

  146. Jafarian Tehrani M, Sternberg EM . Animal models of neuroimmune interaction in inflammatory diseases. J Neuroimmunol 1999; 100: 13–20.

    Article  CAS  PubMed  Google Scholar 

  147. Sternberg EM, Hill JM, Chrousos GP, Kamilaris T, Listwak SJ, Gold PW et al. Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci USA 1989a; 86: 2374–2378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Cash JM, Crofford LJ, Gallucci WT, Sternberg EM, Gold PW, Chrousos GP et al. Pituitary–adrenal axis responsiveness to ovine corticotrophin relearsing hormone in patients with rheumatoid arthritis treated with low dose prednisolone. J Rheumatol 1992; 19: 1692–1696.

    CAS  PubMed  Google Scholar 

  149. Chikanza IC . Mechanisms of corticosteroid resistance in rheumatoid arthritis: a putative role for the corticosteroid receptor beta isoform. Ann NY Acad Sci 2002; 966: 39–48.

    Article  CAS  PubMed  Google Scholar 

  150. Chikanza IC, Petrou P, Kingsley G, Chrousos GP, Panayi GS . Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis. Arthritis Rheum 1992; 35: 1281–1288.

    Article  CAS  PubMed  Google Scholar 

  151. Eijsbouts AM, Murphy E . The role of the hypothalamic-pituitary-adrenal axis in rheumatoid arthritis. Baillieres Best Pract Res Clin Rheumatol 1999; 13: 599–613.

    Article  CAS  PubMed  Google Scholar 

  152. Gutierrez MA, Garcia ME, Rodriguez JA, Mardonez G, Jacobelli S, Rivero S et al. Hypothalamic-pituitary-adrenal axis in patients with active rheumatoid arthritis: a controlled study using insulin hypoglycemia stress test and prolactin stimulation. J Rheumatol 1999; 26: 277–281.

    CAS  PubMed  Google Scholar 

  153. Neeck G, Federlin K, Graef V, Rusch D, Schmidt KL . Adrenal secretion of cortisol in patients with rheumatoid arthritis. J Rheumatol 1990; 17: 24–29.

    CAS  PubMed  Google Scholar 

  154. Johnson EO, Vlachoyiannopoulos PG, Skopouli FN, Tzioufas AG, Moutsopoulos HM . Hypofunction of the stress axis in Sjogren's syndrome. J Rheumatol 1998; 25: 1508–1514.

    CAS  PubMed  Google Scholar 

  155. Gutierrez MA, Garcia ME, Rodriguez JA, Rivero S, Jacobelli S . Hypothalamic-pituitary-adrenal axis function and prolactin secretion in systemic lupus erythematosus. Lupus 1998; 7: 404–408.

    Article  CAS  PubMed  Google Scholar 

  156. Wei T, Lightman SL . The neuroendocrine axis in patients with multiple sclerosis. Brain 1997; 120(Part 6): 1067–1076.

    Article  PubMed  Google Scholar 

  157. Michelson D, Stone L, Galliven E, Magiakou MA, Chrousos GP, Sternberg EM et al. Multiple sclerosis is associated with alterations in hypothalamic-pituitary-adrenal axis function. J Clin Endocrinol Metab 1994; 79: 848–853.

    CAS  PubMed  Google Scholar 

  158. Buske-Kirschbaum A, Geiben A, Hollig H, Morschhauser E, Hellhammer D . Altered responsiveness of the hypothalamus-pituitary-adrenal axis and the sympathetic adrenomedullary system to stress in patients with atopic dermatitis. J Clin Endocrinol Metab 2002; 87: 4245–4251.

    Article  CAS  PubMed  Google Scholar 

  159. Buske-Kirschbaum A, Hellhammer DH . Endocrine and immune responses to stress in chronic inflammatory skin disorders. Ann NY Acad Sci 2003; 992: 231–240.

    Article  CAS  PubMed  Google Scholar 

  160. Buske-Kirschbaum A, Jobst S, Psych D, Wustman A, Kirschbaum C, Rauh W et al. Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis. Psychosom Med 1997; 59: 419–426.

    Article  CAS  PubMed  Google Scholar 

  161. Demitrack MA, Crofford LJ . Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome. Ann NY Acad Sci 1998; 840: 684–697.

    Article  CAS  PubMed  Google Scholar 

  162. Crofford LJ . The hypothalamic-pituitary-adrenal axis in the pathogenesis of rheumatic diseases. Endocrinol Metab Clin N Am 2002; 31: 1–13.

    Article  CAS  Google Scholar 

  163. Demitrack MA . Neuroendocrine correlates of chronic fatigue syndrome: a brief review. J Psychiatr Res 1997; 31: 69–82.

    Article  CAS  PubMed  Google Scholar 

  164. Crofford LJ, Pillemer SR, Kalogeras KT, Cash JM, Michelson D, Kling MA et al. Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthitis Rheum 1994; 37: 1583–1592.

    Article  CAS  Google Scholar 

  165. Straub RH, Herfarth H, Falk W, Andus T, Scholmerich J . Uncoupling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis in inflammatory bowel disease? J Neuroimmunol 2002a; 126: 116–125.

    Article  CAS  PubMed  Google Scholar 

  166. Niess JH, Monnikes H, Dignass AU, Klapp BF, Arck PC . Review on the influence of stress on immune mediators, neuropeptides and hormones with relevance for inflammatory bowel disease. Digestion 2002; 65: 131–140.

    Article  CAS  PubMed  Google Scholar 

  167. Crofford LJ, Young EA, Engleberg NC, Korszun A, Brucksch CB, McCIure LA et al. Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome. Brain Behav Immun 2004; 18: 314–325.

    Article  CAS  PubMed  Google Scholar 

  168. Cleare AJ . The HPA axis and the genesis of chronic fatigue syndrome. Trends Endocrinol Metab 2004; 15: 55–59.

    Article  CAS  PubMed  Google Scholar 

  169. Cleare AJ . The neuroendocrinology of chronic fatigue syndrome. Endocr Rev 2003; 24: 236–252.

    Article  CAS  PubMed  Google Scholar 

  170. Gaab J, Huster D, Peisen R, Engert V, Heitz V, Schad T et al. Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation. Psychosom Med 2002; 64: 951–962.

    CAS  PubMed  Google Scholar 

  171. Neeck G, Crofford LJ . Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin N Am 2000; 26: 989–1002.

    Article  CAS  Google Scholar 

  172. DeRijk RH, Schaaf MJ, Turner G, Datson NA, Vreugdenhil E, Cidlowski J et al. A human glucocorticoid receptor gene variant that increases the stability of the glucocorticoid receptor beta-isoform mRNA is associated with rheumatoid arthritis. J Rheumatol 2001; 28: 2383–2388.

    CAS  PubMed  Google Scholar 

  173. DeRijk RH, Schaaf M, de Kloet ER . Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol 2002; 81: 103–122.

    Article  CAS  PubMed  Google Scholar 

  174. Webster JI, Tonelli LH, Moayeri M, Simons Jr SS, Leppla SH, Sternberg EM . Anthrax lethal factor represses glucocorticoid and progesterone receptor activity. Proc Natl Acad Sci USA 2003; 100: 5706–5711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Gudbjornsson B, Skogseid B, Oberg K, Wide L, Hallgren R . Intact adrenocorticotropic hormone secretion but impaired cortisol response in patients with active rheumatoid arthritis. Effect of glucocorticoids. J Rheumatol 1996; 23: 596–602.

    CAS  PubMed  Google Scholar 

  176. Cutolo M, Foppiani L, Perete C, Ballarino P, SuIIi A, Villaggio B et al. Hypothalamic-pituitary-adrenocortical axis function in premenopausal women with rheumatoid arthritis not treated with glucocortiocids. J Rheumatol 1999; 26: 282–288.

    CAS  PubMed  Google Scholar 

  177. Crofford LJ, Kalogeras KT, Mastorakos G, Magiakou MA, Wells J, Kanik KS et al. Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab 1997; 82: 1279–1283.

    Article  CAS  PubMed  Google Scholar 

  178. Hall J, Morand EF, Medbak S, Zaman M, Perry L, Goulding NJ et al. Abnormal hypothalamic-pituitary-adrenal axis function in rheumatoid arthritis. Effects of nonsteroidal antiinflammatory drugs and water immersion. Arthritis Rheum 1994; 37: 1132–1137.

    Article  CAS  PubMed  Google Scholar 

  179. Harkness JA, Richter MB, Panayi GS, Van de Pette K, Unger A, Pownall R et al. Circadian variation in disease activity in rheumatoid arthritis. Br Med J (Clin Res Edn) 1982; 284: 551–554.

    Article  CAS  Google Scholar 

  180. Morand EF, Leech M . Hypothalamic-pituitary-adrenal axis regulation of inflammation in rheumatoid arthritis. Immunol Cell Biol 2001; 79: 395–399.

    Article  CAS  PubMed  Google Scholar 

  181. Saldanha C, Tougas G, Grace E . Evidence for anti-inflammatory effect of normal circulating plasma cortisol. Clin Exp Rheumatol 1986; 4: 365–366.

    CAS  PubMed  Google Scholar 

  182. Sanden S, Tripmacher R, Weltrich R, Rohde W, Hiepe F, Burmester GR et al. Glucocorticoid dose dependent downregulation of glucocorticoid receptors in patients with rheumatic diseases. J Rheumatol 2000; 27: 1265–1270.

    CAS  PubMed  Google Scholar 

  183. Schlaghecke R, Kornely E, Wollenhaupt J, Specker C . Glucocorticoid receptors in rheumatoid arthritis. Arthritis Rheum 1992; 35: 740–744.

    Article  CAS  PubMed  Google Scholar 

  184. van Everdingen AA, Huisman AM, Wenting MJ, van Reesema S, Jacobs JW, Bijlsma JW . Down regulation of glucocorticoid receptors in early-diagnosed rheumatoid arthritis. Clin Exp Rheumatol 2002; 20: 463–468.

    CAS  PubMed  Google Scholar 

  185. Huisman AM, Van Everdingen AA, Wenting MJ, Siewertsz Van Reesema DR, Lafeber FP et al. Glucocorticoid receptor downregulation in early diagnosed rheumatoid arthritis. Ann NY Acad Sci 2002; 966: 64–67.

    Article  CAS  PubMed  Google Scholar 

  186. Neeck G, Kluter A, Dotzlaw H, Eggert M . Involvement of the glucocorticoid receptor in the pathogenesis of rheumatoid arthritis. Ann NY Acad Sci 2002; 966: 491–495.

    Article  CAS  PubMed  Google Scholar 

  187. Eggert M, Kluter A, Rusch D, Schmidt KL, Dotzlaw H, Schulz M et al. Expression analysis of the glucocorticoid receptor and the nuclear factor-kB subunit p50 in lymphocytes from patients with rheumatoid arthritis. J Rheumatol 2002; 29: 2500–2506.

    CAS  PubMed  Google Scholar 

  188. Straub RH, Paimela L, Peltomaa R, Scholmerich J, Leirisalo-Repo M . Inadequately low serum levels of steroid hormones in relation to interleukin-6 and tumor necrosis factor in untreated patients with early rheumatoid arthritis and reactive arthritis. Arthritis Rheum 2002b; 46: 654–662.

    Article  CAS  PubMed  Google Scholar 

  189. Brennan FM, Maini RN, Feldmann M . Role of pro-inflammatory cytokines in rheumatoid arthritis. Springer Semin Immunopathol 1998; 20: 133–147.

    Article  CAS  PubMed  Google Scholar 

  190. Verhoef CM, van Roon JA, Vianen ME, Lafeber FP, Bijlsma JW . The immune suppressive effect of dexamethasone in rheumatoid arthritis is accompanied by upregulation of interleukin 10 and by differential changes in interferon gamma and interleukin 4 production. Ann Rheum Dis 1999; 58: 49–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. McEwen BS . The brain is an important target of adrenal steroid actions. A comparison of synthetic and natural steroids. Ann NY Acad Sci 1997; 823: 201–213.

    Article  CAS  PubMed  Google Scholar 

  192. Irwin M . Psychoneuroimmunology of depression: clinical implications. Brain Behav Immun 2002; 16: 1–16.

    Article  PubMed  Google Scholar 

  193. Webster JC, Oakley RH, Jewell CM, Cidlowski JA . Proinflammatory cytokines regulate human glucocorticoid receptor gene expression and lead to the accumulation of the dominant negative β isoform: a mechanism for the generation of glucocorticoid resistance. Proc Natl Acad Sci USA 2001; 98: 6865–6870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Cutolo M, Seriolo B, Villaggio B, Pizzorni C, Craviotto C, Sulli A . Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann NY Acad Sci 2002; 966: 131–142.

    Article  CAS  PubMed  Google Scholar 

  195. Cutolo M, Balleari E, Giusti M, Monachesi M, Accardo S . Sex hormone status of male patients with rheumatoid arthritis: evidence of low serum concentrations of testosterone at baseline and after human chorionic gonadotropin stimulation. Arthritis Rheum 1988; 31: 1314–1317.

    Article  CAS  PubMed  Google Scholar 

  196. Spector TD, Perry LA, Tubb G, Silman AJ, Huskisson EC . Low free testosterone levels in rheumatoid arthritis. Ann Rheum Dis 1988; 47: 65–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Seriolo B, Cutolo M, Garnero A, Accardo S . Relationships between serum 17 beta-oestradiol and anticardiolipin antibody concentrations in female patients with rheumatoid arthritis. Rheumatology (Oxford) 1999; 38: 1159–1161.

    Article  CAS  Google Scholar 

  198. Grennan DM, Sanders PA, Thomson W, Dyer PA . Rheumatoid arthritis: inheritance and association with other autoimmune diseases. Dis Markers 1986; 4: 157–162.

    CAS  PubMed  Google Scholar 

  199. Andonopoulos AP, Siambi V, Makri M, Christofidou M, Markou C, Vagenakis AG . Thyroid function and immune profile in rheumatoid arthritis. A controlled study. Clin Rheumatol 1996; 15: 599–603.

    Article  CAS  PubMed  Google Scholar 

  200. Shiroky JB, Cohen M, Ballachey ML, Neville C . Thyroid dysfunction in rheumatoid arthritis: a controlled prospective survey. Ann Rheum Dis 1993; 52: 454–456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Bianchi G, Marchesini G, Zoli M, Falasconi MC, Iervese T, Vecchi F et al. Thyroid involvement in chronic inflammatory rheumatological disorders. Clin Rheumatol 1993; 12: 479–484.

    Article  CAS  PubMed  Google Scholar 

  202. Wellby ML, Kennedy JA, Pile K, True BS, Barreau P . Serum interleukin-6 and thyroid hormones in rheumatoid arthritis. Metabolism 2001; 50: 463–467.

    Article  CAS  PubMed  Google Scholar 

  203. Sternberg EM . Hyperimmune fatigue syndromes: diseases of the stress response? J Rheumatol 1993; 20: 418–421.

    CAS  PubMed  Google Scholar 

  204. Postolache TT, Stiller JW, Herrel R, Goldstein DS, Sheeram SS, Zebrak R et al. Tree pollen peaks are associated with increased nonviolent suicide in women. Mol Psych advanced online publication, 14 December 2004.

  205. Creed F . Psychological disorders in rheumatoid arthritis: a growing consensus? Ann Rheum Dis 1990; 49: 808–812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Gorwood P, Pouchot J, Vinccneux P, Puechal X, Flipo RM, De Bandt M et al. Rheumatoid arthritis and schizophrenia: a negative association at a dimensional level. Schizophr Res 2004; 66: 21–29.

    Article  CAS  PubMed  Google Scholar 

  207. Dickens C, Jackson J, Tomenson B, Hay E, Creed F . Association of depression and rheumatoid arthritis. Psychosomatics 2003; 44: 209–215.

    Article  PubMed  Google Scholar 

  208. Blalock SJ, DeVellis RF . Rheumatoid arthritis and depression: an overview. Bull Rheum Dis 1992; 41: 6–8.

    CAS  PubMed  Google Scholar 

  209. Mindham RH, Bagshaw A, James SA, Swannell AJ . Factors associated with the appearance of psychiatric symptoms in rheumatoid arthritis. J Psychosom Res 1981; 25: 429–435.

    Article  CAS  PubMed  Google Scholar 

  210. Zorrilla EP, Luborsky L, McKay JR, Rosenthal R, Houldin A, Tax A et al. The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun 2001; 15: 199–226.

    Article  CAS  PubMed  Google Scholar 

  211. Herbert TB, Cohen S . Depression and immunity: a meta-analytic review. Psychol Bull 1993; 113: 472–486.

    Article  CAS  PubMed  Google Scholar 

  212. Consensus development conference diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 1993; 94: 636–638.

  213. Ziegler R, Kasperk C . Glucocorticoid-induced osteoporosis: prevention and treatment. Steroids 1998; 63: 344–348.

    Article  CAS  PubMed  Google Scholar 

  214. Cizza G, Ravn P, Chrousos GP, Gold PW . Depression: a major, unrecognized risk factor for osteoporosis? Trends Endocrinol Metab 2001; 12: 198–203.

    Article  CAS  PubMed  Google Scholar 

  215. Harper KD, Weber TJ . Secondary osteoporosis. Diagnostic considerations. Endocrinol Metab Clin N Am 1998; 27: 325–348.

    Article  CAS  Google Scholar 

  216. Chrousos G, Gold PW . The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 1992; 267: 1244–1252.

    Article  CAS  PubMed  Google Scholar 

  217. Chan SD, Chiu DK, Atkins D . Mechanism of the regulation of the 1 alpha,25-dihydroxyvitamin D3 receptor in the rat jejunum by glucocorticoids. J Endocrinol 1984; 103: 295–300.

    Article  CAS  PubMed  Google Scholar 

  218. Mundy GR, Shapiro JL, Bandelin JG, Canalis EM, Raisz LG . Direct stimulation of bone resorption by thyroid hormones. J Clin Invest 1976; 58: 529–534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Bisbocci D, Gallo V, Damiano P, Sidoli L, Cantoni R, Aitno G et al. Spontaneous release of interleukin 1 beta from human blood monocytes in thyrotoxic osteodystrophy. J Endocrinol Invest 1996; 19: 511–515.

    Article  CAS  PubMed  Google Scholar 

  220. Bartalena L, Brogioni S, Grasso L, Martino E . Increased serum interleukin-6 concentration in patients with subacute thyroiditis: relationship with concomitant changes in serum T4-binding globulin concentration. J Endocrinol Invest 1993; 16: 213–218.

    Article  CAS  PubMed  Google Scholar 

  221. Celik I, Akalin S, Erbas T . Serum levels of interleukin 6 and tumor necrosis factor-alpha in hyperthyroid patients before and after propylthiouracil treatment. Eur J Endocrinol 1995; 132: 668–672.

    Article  CAS  PubMed  Google Scholar 

  222. Lakatos P, Foldes J, Horvath C, Kiss L, Tatrai A, Takacs I et al. Serum interleukin-6 and bone metabolism in patients with thyroid function disorders. J Clin Endocrinol Metab 1997; 82: 78–81.

    CAS  PubMed  Google Scholar 

  223. Simsek G, Karter Y, Aydin S, Uzun H . Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism. Chin J Physiol 2003; 46: 181–186.

    CAS  PubMed  Google Scholar 

  224. Sato K, Han DC, Fujii Y, Tsushima T, Shizume K . Thyroid hormone stimulates alkaline phosphatase activity in cultured rat osteoblastic cells (ROS 17/2.8) through 3,5,3′-triiodo-L-thyronine nuclear receptors. Endocrinology 1987; 120: 1873–1881.

    Article  CAS  PubMed  Google Scholar 

  225. Britto JM, Fenton AJ, Holloway WR, Nicholson GC . Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption. Endocrinology 1994; 134: 169–176.

    Article  CAS  PubMed  Google Scholar 

  226. Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y et al. TSH is a negative regulator of skeletal remodeling. Cell 2003; 115: 151–162.

    Article  CAS  PubMed  Google Scholar 

  227. McLeod KJ, Rubin CT, Otter MW, Qin YX . Skeletal cell stresses and bone adaptation. Am J Med Sci 1998; 316: 176–183.

    CAS  PubMed  Google Scholar 

  228. Kurihara N, Bertolini D, Suda T, Akiyama Y, Roodman GD . IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release. J Immunol 1990; 144: 4226–4230.

    CAS  PubMed  Google Scholar 

  229. Pumarino H, Pumarino MG . Cytokines, growth factors, and metabolic bone disease. Rev Med Chile 1996; 124: 248–257.

    CAS  PubMed  Google Scholar 

  230. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL et al. Leptin regulates bone formation via the sympathetic nervous system. Cell 2002; 111: 305–317.

    Article  CAS  PubMed  Google Scholar 

  231. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000; 100: 197–207.

    Article  CAS  PubMed  Google Scholar 

  232. Harbuz MS, Windle RJ, Jessop DS, Renshaw D, Ingram CD, Lightman SL . Differential effects of psychological and immunological challenge on the hypothalamo-pituitary-adrenal axis function in adjuvant-induced arthritis. Ann NY Acad Sci 1999; 876: 43–52.

    Article  CAS  PubMed  Google Scholar 

  233. Sternberg EM, Young WSd, Bernardini R, Calogero AE, Chrousos GP, Gold PW et al. A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc Natl Acad Sci USA 1989b; 86: 4771–4775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Aksentijevich S, Whitfield HJJ, Youag WSI, Wilder RL, Chrousos GP, Gold PW et al. Arthritis-susceptible Lewis rats fail to emerge from the stress hyporesponsive period. Dev Brain Res 1992; 65: 115–118.

    Article  CAS  Google Scholar 

  235. Stefferl A, Linington C, Holsboer F, Reul JM . Susceptibility and resistance to experimental allergic encephalomyelitis: Relationship with hypothalamic-pituitary-adrenocortical axis responsiveness in the rat. Endocrinology 1999; 140: 4932–4938.

    Article  CAS  PubMed  Google Scholar 

  236. Misiewicz B, Poltorak M, Raybourne RB, Gomez M, Listwak S, Sternberg EM . Intracerebroventricular transplantation of embryonic neuronal tissue from inflammatory resistant into inflammatory susceptible rats suppresses specific components of inflammation. Exp Neurol 1997; 146: 305–314.

    Article  CAS  PubMed  Google Scholar 

  237. Diaz-Borjon A, Richaud-Patin Y, Alvarado de la Barrera C, Jakez-Ocampo J, Ruiz-Arguelles A, Llorente L . Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part II: increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control. Jt Bone Spine 2000; 67: 40–48.

    CAS  Google Scholar 

  238. Lee YM, Fujiwara J, Munakata Y, Ishii T, Sugawara A, Kaku M et al. A mutation of the glucocorticoid receptor gene in patients with systemic lupus erythematosus. Tohoku J Exp Med 2004; 203: 69–76.

    Article  CAS  PubMed  Google Scholar 

  239. Jiang T, Liu S, Tan M, Huang F, Sun Y, Dong X et al. The phase-shift mutation in the glucocorticoid receptor gene: potential etiologic significance of neuroendocrine mechanisms in lupus nephritis. Clin Chim Acta 2001; 313: 113–117.

    Article  CAS  PubMed  Google Scholar 

  240. Mingrone G, DeGaetano A, Pugeat M, Capristo E, Greco AV, Gasbarrini G . The steroid resistance of Crohn's disease. J Invest Med 1999; 47: 319–325.

    CAS  Google Scholar 

  241. Leung DY, Szefler SJ . Diagnosis and management of steroid-resistant asthma. Clin Chest Med 1997; 18: 611–625.

    Article  CAS  PubMed  Google Scholar 

  242. Barnes PJ . Inhaled glucocorticoids for asthma. N Engl J Med 1995; 332: 868–875.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Section on Neuroendocrine Immunology and Behavior, Integrative Neural Immune Program, National Institute of Mental Health, NIH, Bethesda, MD, USA

    A Marques-Deak & E Sternberg

  2. Center of Endocrinology Branch, National Institute of Diabetes, and Digestive Kidney Diseases, NIH, Bethesda, MD, USA

    G Cizza

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  1. A Marques-Deak
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  2. G Cizza
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  3. E Sternberg
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Correspondence to E Sternberg.

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Marques-Deak, A., Cizza, G. & Sternberg, E. Brain-immune interactions and disease susceptibility. Mol Psychiatry 10, 239–250 (2005). https://doi.org/10.1038/sj.mp.4001643

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  • DOI: https://doi.org/10.1038/sj.mp.4001643

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