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Vol. 16, No. 5, 2009
Issue release date: June 2009

Single Nucleotide Polymorphisms Related to HPA Axis Reactivity

DeRijk R.H.
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Abstract

A very important question in the neuroendocrinology of stress-related disorders is why some individuals thrive and others break down under similar adverse conditions. The hypothalamic-pituitary-adrenal (HPA) axis is the central component of the stress system, displaying extensive variability in reactivity among human subjects. Common gene variants have been associated with several changes in HPA axis reactivity. These gene variants are identified in the GABAA receptor, the μ-opioid receptor, the serotonin transporter, catechol O-methyltransferase (COMT), monoamine oxidase (MAOA), the α2-adrenergic receptor, brain-derived neurotrophic factor and the anginotensin-converting enzyme. Most extensively studied are genetic variants of the two central corticosteroid receptors, the high-affinity mineralocorticoid receptor (MR) and the lower-affinity glucocorticoid receptor (GR). In the GR, the TthIIII, NR3C1-1, ER22/23EK, N363S, BclI and the A3669G, and in the MR, the –2 G/C and the I180V all modify HPA axis responsiveness at several levels. As a result of these genetic variants, HPA axis reactivity will be changed exposing not only the brain but the whole body to suboptimal cortisol levels during challenges. We propose that these genetic variants which modulate HPA axis reactivity are part of the genetic makeup that determines individual stress responsivity and coping style, affecting vulnerability to disease.



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References

  1. De Kloet ER, Joëls M, Holsboer F: Stress and the brain: from adaptation to disease. Nat Rev Neurosci 2005;6:463–475.
  2. Priftis KN, Papadimitriou A, Nicolaidou P, Chrousos GP: The hypothalamic-pituitary-adrenal axis in asthmatic children. Trends Endocrinol Metab 2008;19:32–38.
  3. De Kloet ER, DeRijk RH, Meijer OC: Therapy insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression? Nat Clin Pract Endocrinol Metab 2007;3:168–179.
  4. Dallman MF, Viau VG, Bhatnagar S, Gomez F, Laugero K, Bell ME: Corticotropin-releasing factor, corticosteroids, stress and sugar: energy balance, the brain and behavior; in Pfaff D (ed): Hormones, Brain and Behavior. San Diego, Elsevier, 2002, vol 1, pp 571–631.
  5. Kalsbeek A, Palm IF, la Fleur SE, Scheer FA, Perreau-Lenz S, Ruiter M, Kreier F, Cailotto C, Buijs RM: SCN outputs and the hypothalamic balance of life. J Biol Rhythms 2006;21:458–469.
  6. Lightman SL, Wiles CC, Atkinson HC, Henley DE, Russell GM, Leendertz JA, McKenna MA, Spiga F, Wood SA, Conway-Campbell BL: The significance of glucocorticoid pulsatility. Eur J Pharmacol 2008;583:255–262.
  7. Veldhuis JD, Iranmanesh A, Lizarralde G, Johnson ML: Amplitude modulation of a burst-like mode of cortisol secretion subserves the circadian glucocorticoid rhythm. Am J Physiol 1989;257:E6–E14.
  8. Ratka A, Sutanto W, Bloemers M, de Kloet ER: On the role of the brain type I and type II corticosteroid receptors in neuroendocrine regulation. Neuroendocrinology 1989;50:117–123.
  9. Karst H, Berger S, Turiault M, Tronche F, Schütz G, Joëls M: Mineralocorticoid receptors are indispensible for non-genomic modulation of hippocampal glutamate transmission by corticosterone. Proc Natl Acad Sci USA 2005;102:19204–19207.
  10. Atkinson HC, Wood SA, Castrique ES, Kershaw YM, Wiles CC, Lightman SL: Corticosteroids mediate fast feedback of the rat hypothalamic-pituitary-adrenal axis via the mineralocorticoid receptor. Am J Physiol 2008;294:E1011–E1022.
  11. Spiga F, Harrison LR, Wood SA, MacSweeney CP, Thomson FJ, Craighead M, Grassie M, Lightman SL: Effect of the glucocorticoid receptor antagonist Org-34850 on fast and delayed feedback of corticosterone release. J Endocrinol 2008;196:323–330.
  12. Joëls M, Karst H, Derijk R, de Kloet ER: The coming out of the brain mineralocorticoid receptor. Trends Neurosci 2008;31:1–7.
  13. Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, Cullinan WE: Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol 2003;24:151–180.
  14. Pacak K, Palkovits M: Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocr Rev 2001;22:502–548.
  15. Brunton PJ, Russell JA: Attenuated hypothalamo-pituitary-adrenal axis responses to immune challenge during pregnancy: the neurosteroid opioid connection. J Physiol 2008;586:369–375.
  16. Aguilera G, Kiss A, Luo X, Akbasak BS: The renin angiotensin system and the stress response. Ann NY Acad Sci 1995;771:173–186.
  17. Reul JM, de Kloet ER: Two receptor systems for corticosterone in the rat brain: microdistribution and differential occupation. Endocrinology 1985;117:2505–2511.
  18. Heuser I, Deuschle M, Weber B, Stalla GK, Holsboer F: Increased activity of the hypothalamus-pituitary-adrenal system after treatment with the mineralocorticoid receptor antagonist spironolactone. Psychoneuroendocrinology 2000;25:513–518.
  19. De Kloet ER, de Kock S, Schild V, Veldhuis HD: Antiglucocorticoid RU-38486 attenuates retention of a behaviour and disinhibits the hypothalamic-pituitary adrenal axis at different brain sites. Neuroendocrinology 1988;47:109–115.
  20. Van Haarst AD, Oitzl MS, de Kloet ER: Facilitation of feedback inhibition through blockade of glucocorticoid receptors in the hippocampus. Neurochem Res 1997;22:1323–1328.
  21. Oitzl MS, van Haarst AD, Sutanto W, de Kloet ER: Corticosterone, brain mineralocorticoid receptors (MRs) and the activity of the hypothalamic-pituitary-adrenal (HPA) axis: the Lewis rat as an example of increased central MR capacity and a hyporesponsive HPA axis. Psychoneuroendocrinology 1995;20:655–675.
  22. Tasker JG, Di S, Malcher-Lopes R: Rapid glucocorticoid signaling via membrane-associated receptors. Endocrinology 2006;147:5549–5556.
  23. Dallman MF: Fast glucocorticoid actions on brain: back to the future. Front Neuroendocrinol 2005;26:103–108.
  24. Torpy DJ, Ho JT: Corticosteroid-binding globulin gene polymorphisms: clinical implications and links to idiopathic chronic fatigue disorders. Clin Endocrinol (Oxf) 2007;67:161–167.
  25. De Kloet ER: Why dexamethasone poorly penetrates the brain. Stress 1997;2:13–20.
  26. Seckl JR, Walker BR: 11-Beta-hydroxysteroid dehydrogenase type 1 – a tissue-specific amplifier of glucocorticoid action. Endocrinology 2001;142:1371–1376.
  27. Morton NM, Paterson J, Masuzaki H, Holmes MC, Staels B, Fievet C, Walker B, Mullins JJ, Seckl JR: Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11β-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes 2004;53:931–938.
  28. Edwards CR, Steward PM, Burt D, Brett L, McIntyre MA, Sutanto W, de Kloet ER, Monder C: Localisation of 11β-hydroxysteroid dehydrogenase – tissue-specific protector of the mineralocorticoid receptor. Lancet 1988;2:986–989.
  29. Fiebeler A, Schmidt F, Muller DN, Park JK, Dechend R, Bieringer M, Shagdarsuren E, Breu V, Haller H, Luft FC: Mineralocorticoid receptor affects AP-1 and nuclear factor-κB activation in angiotensin II-induced cardiac injury. Hypertension 2001;37:787–793.
  30. Pascual-Le Tallec L, Lombes M: The mineralocorticoid receptor: a journey exploring its diversity and specificity of action. Mol Endocrinol 2005;19:2211–2221.
  31. Meijer OC, van der Laan S, Lachize S, Steenbergen PJ, de Kloet ER: Steroid receptor coregulator diversity: what can it mean for the stressed brain? Neurosci 2006;138:891–899.
  32. Heitzer MD, Wolf IM, Sanchez ER, Witchel SF, Defranco DB: Glucocorticoid receptor physiology. Rev Endocr Metab Disord 2007;8:321–330.
  33. Viengchareun S, Le MD, Martinerie L, Munier M, Pascual-Le TL, Lombes M: The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology. Nucl Recept Signal 2007;5:e012.
  34. Van der Laan S, Meijer OC: Pharmacology of glucocorticoids: beyond receptors. Eur J Pharmacol 2008;585:483–491.
  35. Meijer OC: Understanding stress through the genome. Stress 2006;9:61–67.
  36. De Kloet ER, Sarabdjitsingh RA: Everything has rhythm: focus on glucocorticoid pulsatility. Endocrinology 2008;149:3241–3243.
  37. Wilhelm I, Born J, Kudielka BM, Schlotz W, Wust S: Is the cortisol awakening rise a response to awakening? Psychoneuroendocrinology 2007;32:358–366.
  38. Carroll BJ, Feinberg M, Greden JF, Tarika J, Albala AA, Haskett RF, James NM, Kronfol Z, Lohr N, Steiner M, de Vigne JP, Young EA: A specific laboratory test for the diagnosis of melancholia. Arch Gen Psychiatry 1981;38:15–22.
  39. Holsboer F, von Bardeleben U, Wiedemann K, Muller OA, Stalla GK: Serial assessment of corticotropin-releasing hormone response after dexamethasone in depression. Implications for pathophysiology of DST nonsuppression. Biol Psychiatry 1987;22:228–234.
  40. Holsboer F, Gerken A, Steiger A, Benkert O, Muller OA, Stalla GK: Corticotropin-releasing factor induced pituitary-adrenal response in depression. Lancet 1984;1:55.
  41. Gonzalbez J, Villabona C, Ramon J, Navarro MA, Gimenez O, Ricart W, Soler J: Establishment of reference values for standard dose short synacthen test (250 μg), low-dose short synacthen test (1 μg) and insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects. Clin Endocrinol (Oxf) 2000;53:199–204.
  42. Petrides JS, Gold PW, Mueller GP, Singh A, Chrousos GP, Deutser PA: Marked differences in functioning of the hypothalamic-pituitary-adrenal axis between groups of men. J Appl Physiol 1997;82:1979–1988.
  43. Dickerson SS, Kemeny ME: Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull 2005;130:355–391.

    External Resources

  44. Federenko IS, Nagamine M, Hellhammer DH, Wadhwa PD, Wust S: The heritability of hypothalamus pituitary adrenal axis responses to psychosocial stress is context dependent. J Clin Endocrinol Metab 2004;89:6244–6250.
  45. Feuk L, Marshall CR, Wintle RF, Scherer SW: Structural variants: changing the landscape of chromosomes and design of disease studies. Hum Mol Genet 2006;15(Spec No 1):R57–R66.
  46. Muller-Myhsok B: The usefulness of single nucleotide polymorphisms for genetic epidemiological investigation of complex psychiatric diseases. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:1017–1020.
  47. Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM: A ‘silent’ polymorphism in the MDR1 gene changes substrate specificity. Science 2007;315:525–528.
  48. Rosmond R, Bouchard C, Bjorntorp P: Association between a variant at the GABA(A)- α6 receptor subunit gene, abdominal obesity, and cortisol secretion. Ann NY Acad Sci 2002;967:566–570.
  49. Uhart M, McCaul ME, Oswald LM, Choi L, Wand GS: GABRA6 gene polymorphism and an attenuated stress response. Mol Psychiatry 2004;9:998–1006.
  50. Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L: Single-nucleotide polymorphism in the human μ-opioid receptor gene alters β-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA 1998;95:9608–9613.
  51. Chong RY, Oswald L, Yang X, Uhart M, Lin PI, Wand GS: The μ-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress. Neuropsychopharmacology 2006;31:204–211.
  52. Wand GS, McCaul M, Yang X, Reynolds J, Gotjen D, Lee S, Ali A: The μ-opioid receptor gene polymorphism (A118G) alters HPA axis activation induced by opioid receptor blockade. Neuropsychopharmacology 2002;26:106–114.
  53. Hernandez-Avila CA, Wand G, Luo X, Gelernter J, Kranzler HR: Association between the cortisol response to opioid blockade and the Asn40Asp polymorphism at the μ-opioid receptor locus (OPRM1). Am J Med Genet B Neuropsychiatr Genet 2003;118B:60–65.
  54. Hernandez-Avila CA, Covault J, Wand G, Zhang H, Gelernter J, Kranzler HR: Population-specific effects of the Asn40Asp polymorphism at the mu-opioid receptor gene (OPRM1) on HPA-axis activation. Pharmacogenet Genomics 2007;17:1031–1038.
  55. Murphy DL, Lesch KP: Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 2008;9:85–96.
  56. Barr CS, Newman TK, Shannon C, Parker C, Dvoskin RL, Becker ML, Schwandt M, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD: Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biol Psychiatry 2004;55:733–738.
  57. Barr CS, Newman TK, Schwandt M, Shannon C, Dvoskin RL, Lindell SG, Taubman J, Thompson B, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD: Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques. Proc Natl Acad Sci USA 2004;101:12358–12363.
  58. Jarrell H, Hoffman JB, Kaplan JR, Berga S, Kinkead B, Wilson ME: Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys. Physiol Behav 2008;93:807–819.
  59. O’Hara R, Schroder CM, Mahadevan R, Schatzberg AF, Lindley S, Fox S, Weiner M, Kraemer HC, Noda A, Lin X, Gray HL, Hallmayer JF: Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol. Mol Psychiatry 2007;12:544–555.
  60. Jabbi M, Korf J, Kema IP, Hartman C, van der PG, Minderaa RB, Ormel J, Den Boer JA: Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA. Mol Psychiatry 2007;12:483–490.
  61. Rosmond R, Bouchard C, Bjorntorp P: A C-1291G polymorphism in the α2A-adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels. J Intern Med 2002;251:252–257.
  62. Schmidt HD, Duman RS: The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol 2007;18:391–418.
  63. Schule C, Zill P, Baghai TC, Eser D, Zwanzger P, Wenig N, Rupprecht R, Bondy B: Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients. Psychoneuroendocrinology 2006;31:1019–1025.
  64. Vinson GP: Angiotensin II, corticosteroids, type II diabetes and the metabolic syndrome. Med Hypotheses 2007;68:1200–1207.
  65. Baghai TC, Binder EB, Schule C, Salyakina D, Eser D, Lucae S, Zwanzger P, Haberger C, Zill P, Ising M, Deiml T, Uhr M, Illig T, Wichmann HE, Modell S, Nothdurfter C, Holsboer F, Muller-Myhsok B, Moller HJ, Rupprecht R, Bondy B: Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism. Mol Psychiatry 2006;11:1003–1015.
  66. Baghai TC, Schule C, Zwanzger P, Minov C, Zill P, Ella R, Eser D, Oezer S, Bondy B, Rupprecht R: Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. Neurosci Lett 2002;328:299–303.
  67. DeRijk RH, de Kloet ER: Corticosteroid receptor polymorphisms: determinants of vulnerability and resilience. Eur J Pharmacol 2008;853:303–311.

    External Resources

  68. Bamberger CM, Schulte HM, Chrousos GP: Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245–261.
  69. Zennaro MC, Le Menuet D, Lombes M: Characterization of the human mineralocorticoid receptor gene 5′-regulatory region: evidence for differential hormonal regulation of two alternative promoters via nonclassical mechanisms. Mol Endocrinol 1996;10:1549–1560.
  70. Castren M, Damm K: A functional promoter directing expression of a novel type of rat mineralocorticoid receptor mRNA in brain. J Neuroendocrinol 1993;5:461–466.
  71. Turner JD, Muller CP: Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple human exon 1. J Mol Endocrinol 2005;283–289.
  72. Van Leeuwen N, Wust S, Meijer OC, de Kloet ER, Zitman FG, de Rijk RH: The role of single nucleotide polymorphisms in the mineralocorticoid receptor in stress response and psychopathology. Am J Med Genet B Neuropsychiatr Genet 2006;141B:752.
  73. Kuningas M, DeRijk RH, Westendorp RG, Jolles J, Slagboom EP, van Heemst D: Mental performance in old age is dependent on cortisol and genetic variance in the mineralocorticoid and glucocorticoid receptors. Neuropsychopharmacology 2007;32:1–7.
  74. DeRijk RH, Wüst S, Meijer OC, Zennaro MC, Federenko IS, Hellhammer DH, Giacchetti G, Vreugdenhil E, Zitman FG, de Kloet ER: A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness. J Clin Endocrinol Metab 2006;91:5083–5089.
  75. Arai K, Nakagomi Y, Iketani M, Shimura Y, Amemiya S, Ohyama K, Shibasaki T: Functional polymorphisms in the mineralocorticoid receptor and amirolide-sensitive sodium channel genes in a patient with sporadic pseudohypoaldosteronism. Hum Genet 2003;112:91–97.
  76. Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, Kajantie E: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. J Clin Endocrinol Metab 2006;91:4544–4551.
  77. Zobel A, Jessen F, von Widdern O, Schuhmacher A, Hofels S, Metten M, Rietschel M, Scheef L, Block W, Becker T, Schild HH, Maier W, Schwab SG: Unipolar depression and hippocampal volume: impact of DNA sequence variants of the glucocorticoid receptor gene. Am J Med Genet B Neuropsychiatr Genet 2008;147B:836–843.
  78. Van Rossum EFC, Lamberts SW: Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res 2004;59:333–357.
  79. Rosmond R, Chagnon YC, Chagnon M, Pérusse L, Bouchard C, Björntorp P: A polymorphism of the 5′-flanking region of the glucocorticoid receptor gene locus is associated with basal cortisol secretion in men. Metabolism 2000;49:1197–1199.
  80. Van West D, Van Den EF, Del Favero J, Souery D, Norrback KF, van Duijn C, Sluijs S, Adolfsson R, Mendlewicz J, Deboutte D, Van Broeckhoven C, Claes S: Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression. Neuropsychopharmacology 2006;31:620–627.
  81. Kumsta R, Entringer S, Koper JW, van Rossum EF, Hellhammer DH, Wust S: Glucocorticoid receptor gene polymorphisms and glucocorticoid sensitivity of subdermal blood vessels and leukocytes. Biol Psychol 2008;79:179–184.
  82. Kumsta R, Entringer S, Koper JW, van Rossum EFC, Hellhammer DH, Wüst S: Sex-specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychological stress. Biol Psychiatry 2007;62:863–869.
  83. Russcher H, Smit P, van den Akker ELT, van Rossum EFC, Brinkman AO, de Jong FH, Lamberts SW, Koper JW: Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression. J Clin Endocrinol Metab 2005;90:5804–5810.
  84. Van den Akker EL, Russcher H, van Rossum EF, Brinkmann AO, de Jong FH, Hokken A, Pols HA, Koper JW, Lamberts SW: Glucocorticoid receptor polymorphism affects transrepression but not transactivation. J Clin Endocrinol Metab 2006;91:2800–2803.
  85. Van Winsen LL, Hooper-van Veen T, van Rossum EF, Polman CH, van den Berg TK, Koper JW, Uitdehaag BM: The impact of glucocorticoid receptor gene polymorphisms on glucocorticoid sensitivity is outweighted in patients with multiple sclerosis. J Neuroimmunol 2005;167:150–156.
  86. Jewell CM, Cidlowski JA: Molecular evidence for a link between the N363S glucocorticoid receptor polymorphism and altered gene expression. J Clin Endocrinol Metab 2007;92:3268–3277.
  87. Huizenga NA, Koper JW, de Lange P, Pols HA, Stolk RP, Burger H, Grobbee DE, Brinkman AO, de Jong FH, Lamberts SW: A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 1998;83:144–151.
  88. Wüst S, van Rossum EFC, Federenko I, Koper JW, Kumsta R, Hellhammer D: Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress. J Clin Endocrinol Metab 2004;89:563–564.
  89. Panarelli M, Holloway CD, Fraser R, Connell JMC, Ingram M, Anderson NN, Kenyon CJ: Glucocorticoid receptor polymorphism, skin vasoconstriction and other metabolic intermediate phenotypes in normal subjects. J Clin Endocrinol Metab 1998;83:1846–1852.
  90. Stevens A, Ray DW, Zeggini E, John S, Richards HL, Griffiths CEM, Donn R: Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype. J Clin Endocrinol Metab 2004;89:892–897.
  91. DeRijk RH, Schaaf M, Turner G, Datson NA, Vreugdenhil E, Cidlowski JA, de Kloet ER, Emery P, Sternberg EM, Detera-Wadleigh S: A glucocorticoid receptor variant that increases the stability of the glucocorticoid receptor β-isoform is associated with rheumatoid arthritis. J Rheum 2001;28:2383–2388.
  92. Van Rossum EFC, Binder EB, Majer M, Koper JW, Ising M, Modell S, Salyakina D, Lamberts SW, Holsboer F: Polymorphisms of the glucocorticoid receptor gene and major depression. Biol Psychiatry 2006;59:681–688.
  93. Binder EB, Salyakina D, Lichterner P, Wochink GM, Ising M, Pütz B, Papiol S, Seaman S, Lucea S, Kohli MA, Nickel T, Künzel HE, Fuchs B, Majer M, Pfennig A, Kern N, Brunner J, Modell S, Baghai T, Deiml T, Zill P, Bondy B, Rupprecht R, Messer T, Köhnlein O, Dabithz H, Brückl T, Müller N, Pfister H, Lieb R, Mueller JC, Lohmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B: Polymorphism in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 2004;36:1319–1325.
  94. Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, Ressler KJ: Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008;299:1291–1305.


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