European Neuropsychopharmacology
Volume 20, Issue 6 , Pages 379-387 , June 2010

Antidepressants, but not antipsychotics, modulate GR function in human whole blood: An insight into molecular mechanisms

  • L.A. Carvalho

      Affiliations

    • Section of Perinatal Psychiatry & Stress, Psychiatry and Immunology Laboratory, King's College London, Institute of Psychiatry, London, UK
    • Corresponding Author InformationCorresponding author. Section of Perinatal Psychiatry & Stress, Psychiatry and Immunology Laboratory, Centre for the Cellular Basis of Behaviour, The James Black Centre, King's College London, Institute of Psychiatry, 125 Coldharbour Lane, SE5 9NU, London, UK. Tel.: +44 20 7848 0352; fax: +44 20 7848 0986.
  • ,
  • B.A. Garner

      Affiliations

    • Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia
  • ,
  • T. Dew

      Affiliations

    • Laboratory of Biochemistry, King's College London, London, UK
  • ,
  • H. Fazakerley

      Affiliations

    • Section of Perinatal Psychiatry & Stress, Psychiatry and Immunology Laboratory, King's College London, Institute of Psychiatry, London, UK
  • ,
  • C.M. Pariante

      Affiliations

    • Section of Perinatal Psychiatry & Stress, Psychiatry and Immunology Laboratory, King's College London, Institute of Psychiatry, London, UK

Received 26 August 2009 ,Revised 5 February 2010 ,Accepted 10 February 2010.

References 

  1. Aihara M, Ida I, Yuuki N, Oshima A, Kumano H, Takahashi K, et al. HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic/paralimbic regions. Psychiatry Res. 2007;155:245–256
  2. Allen JA, Halverson-Tamboli RA, Rasenick MM. Lipid raft microdomains and neurotransmitter signalling. Nat. Rev. Neurosci. 2007;8:128–140
  3. Augustyn M, Otczyk M, Budziszewska B, Jagla G, Nowak W, Basta-Kaim A, et al. Effects of some new antidepressant drugs on the glucocorticoid receptor-mediated gene transcription in fibroblast cells. Pharmacol. Rep. 2005;57:766–773
  4. Avella J, Lehrer M, Katz M, Minden E. Two cases involving clomipramine intoxication. J. Anal. Toxicol. 2004;28:504–508
  5. Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Putz B, et al. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat. Genet. 2004;36:1319–1325
  6. Budziszewska B. Effect of antidepressant drugs on the hypothalamic–pituitary–adrenal axis activity and glucocorticoid receptor function. Pol. J. Pharmacol. 2002;54:343–349
  7. Budziszewska B, Basta-Kaim A, Kubera M, Jaworska L, Leskiewicz M, Tetich M, et al. Effect of lipopolysaccharide and antidepressant drugs on glucocorticoid receptor-mediated gene transcription. Pharmacol. Rep. 2005;57:540–544
  8. Carvalho LA, Pariante CM. In vitro modulation of the glucocorticoid receptor by antidepressants. Stress. 2008;11:411–424
  9. Carvalho LA, Juruena MF, Papadopoulos A, Poon L, Kerwin RW, Cleare A, et al. Clomipramine in vitro reduces glucocorticoid receptor function in healthy subjects but not in patients with major depression. Neuropsychopharmacology. 2008;33:3182–3189
  10. Carvalho LA, Juruena MF, Papadopoulos A, Poon L, Cleare A, Pariante CM. Clomipramine and glucocorticoid receptor function. Neuropsychopharmacology. 2009;34:2194–2195
  11. Castanon N, Konsman JP, Medina C, Chauvet N, Dantzer R. Chronic treatment with the antidepressant tianeptine attenuates lipopolysaccharide-induced Fos expression in the rat paraventricular nucleus and HPA axis activation. Psychoneuroendocrinology. 2003;28:19–34
  12. Castanon N, Leonard BE, Neveu PJ, Yirmiya R. Effects of antidepressants on cytokine production and actions. Brain Behav. Immun. 2002;16:569–574
  13. Chen J, Rasenick MM. Chronic antidepressant treatment facilitates G protein activation of adenylyl cyclase without altering G protein content. J. Pharmacol. Exp. Ther. 1995;275:509–517
  14. Chen J, Rasenick MM. Chronic treatment of C6 glioma cells with antidepressant drugs increases functional coupling between a G protein (Gs) and adenylyl cyclase. J. Neurochem. 1995;64:724–732
  15. Conceptual Framework of Adrenal Stress Index, 2010. Index. Diagnos- Techs Web site. http://www.diagnostechs.com/main.htm.
  16. Dantzer R, O'Connor JC, Freund JJ, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 2008;9:46–57
  17. Donati RJ, Rasenick MM. G protein signaling and the molecular basis of antidepressant action. Life Sci. 2003;73:1–17
  18. Donati RJ, Rasenick MM. Chronic antidepressant treatment prevents accumulation of gsalpha in cholesterol-rich, cytoskeletal-associated, plasma membrane domains (lipid rafts). Neuropsychopharmacology. 2005;30:1238–1245
  19. Dong Y, Aronsson M, Gustafsson JA, Okret S. The mechanism of cAMP-induced glucocorticoid receptor expression. Correlation to cellular glucocorticoid response. J. Biol. Chem. 1989;264:13679–13683
  20. Edgar VA, Sterin-Borda L, Cremaschi GA, Genaro AM. Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation. Eur. J. Pharmacol. 1999;372:65–73
  21. Funato H, Kobayashi A, Watanabe Y. Differential effects of antidepressants on dexamethasone-induced nuclear translocation and expression of glucocorticoid receptor. Brain Res. 2006;1117:125–134
  22. Gold PW, Goodwin FK, Chrousos GP. Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (1). N. Engl. J. Med. 1988;319:348–353
  23. Heiske A, Jesberg J, Krieg JC, Vedder H. Differential effects of antidepressants on glucocorticoid receptors in human primary blood cells and human monocytic u-937 cells. Neuropsychopharmacology. 2003;28:807–817
  24. Hennings JM, Owashi T, Binder EB, Horstmann S, Menke A, Kloiber S, et al. Clinical characteristics and treatment outcome in a representative sample of depressed inpatients — findings from the Munich Antidepressant Response Signature (MARS) project. J. Psychiatr. Res. 2009;43:215–229
  25. Hernandez ME, Mendieta D, Martinez-Fong D, Loria F, Moreno J, Estrada I, et al. Variations in circulating cytokine levels during 52week course of treatment with SSRI for major depressive disorder. Eur. Neuropsychopharmacol. 2008;18:917–924
  26. Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000;23:477–501
  27. 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
  28. Ising M, Kunzel HE, Binder EB, Nickel T, Modell S, Holsboer F. The combined dexamethasone/CRH test as a potential surrogate marker in depression. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2005;29:1085–1093
  29. Klemm P, Harris HJ, Perretti M. Effect of rolipram in a murine model of acute inflammation: comparison with the corticoid dexamethasone. Eur. J. Pharmacol. 1995;281:69–74
  30. Kung TT, Crawley Y, Luo B, Young S, Kreutner W, Chapman RW. Inhibition of pulmonary eosinophilia and airway hyperresponsiveness in allergic mice by rolipram: involvement of endogenously released corticosterone and catecholamines. Br. J. Pharmacol. 2000;130:457–463
  31. Laemont KD, Schaefer CJ, Juneau PL, Schrier DJ. Effects of the phosphodiesterase inhibitor rolipram on streptococcal cell wall-induced arthritis in rats. Int. J. Immunopharmacol. 1999;21:711–725
  32. Lai M, McCormick JA, Chapman KE, Kelly PAT, Seckl JR, Yau JLW. Differential regulation of corticosteroid receptors by monoamine neurotransmitters and antidepressant drugs in primary hippocampal culture. Neuroscience. 2003;118:975–984
  33. Linkowski P, Mendlewicz J, Kerkhofs M, Leclercq R, Golstein J, Brasseur M, et al. 24-hour profiles of adrenocorticotropin, cortisol, and growth hormone in major depressive illness: effect of antidepressant treatment. J. Clin. Endocrinol. Metab. 1987;65:141–152
  34. Mason BL, Pariante CM. The effects of antidepressants on the hypothalamic–pituitary–adrenal axis. Drug News Perspect. 2006;19:603–608
  35. Menkes DB, Rasenick MM, Wheeler MA, Bitensky MW. Guanosine triphosphate activation of brain adenylate cyclase: enhancement by long-term antidepressant treatment. Science. 1983;219:65–67
  36. Meyers JA, Taverna J, Chaves J, Makkinje A, Lerner A. Phosphodiesterase 4 inhibitors augment levels of glucocorticoid receptor in B cell chronic lymphocytic leukemia but not in normal circulating hematopoietic cells. Clin. Cancer Res. 2007;13:4920–4927
  37. Miller AH, Vogt GJ, Pearce BD. The phosphodiesterase type 4 inhibitor, rolipram, enhances glucocorticoid receptor function. Neuropsychopharmacology. 2002;27:939–948
  38. Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol. Psychiatry. 2006;11:680–684
  39. Murphy BE. Steroids and depression. J. Steroid Biochem. Mol. Biol. 1991;38:537–559
  40. Nemeroff CB. The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol. Psychiatry. 1996;1:336–342
  41. Nestler EJ, Terwilliger RZ, Duman RS. Chronic antidepressant administration alters the subcellular distribution of cyclic AMP-dependent protein kinase in rat frontal cortex. J. Neurochem. 1989;53:1644–1647
  42. Nibuya M, Nestler EJ, Duman RS. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J. Neurosci. 1996;16:2365–2372
  43. Okuyama-Tamura M, Mikuni M, Kojima I. Modulation of the human glucocorticoid receptor function by antidepressive compounds. Neurosci. Lett. 2003;342:206–210
  44. Pace TW, Hu F, Miller AH. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav. Immun. 2007;21:9–19
  45. Pariante CM. Glucocorticoid receptor function in vitro in patients with major depression. Stress. 2004;7:209–219
  46. Pariante CM, Miller AH. Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol. Psychiatry. 2001;49:391–404
  47. Pariante CM, Pearce BD, Pisell TL, Owens MJ, Miller AH. Steroid-independent translocation of the glucocorticoid receptor by the antidepressant desipramine. Mol. Pharmacol. 1997;52:571–581
  48. Pariante CM, Makoff A, Lovestone S, Feroli S, Heyden A, Miller AH, et al. Antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporters. Br. J. Pharmacol. 2001;134:1335–1343
  49. Pariante CM, Hye A, Williamson R, Makoff A, Lovestone S, Kerwin RW. The antidepressant clomipramine regulates cortisol intracellular concentrations and glucocorticoid receptor expression in fibroblasts and rat primary neurones. Neuropsychopharmacology. 2003;28:1553–1561
  50. Pariante CM, Kim RB, Makoff A, Kerwin RW. Antidepressant fluoxetine enhances glucocorticoid receptor function in vitro by modulating membrane steroid transporters. Br. J. Pharmacol. 2003;139:1111–1118
  51. Pariante CM, Papadopoulos AS, Poon L, Cleare AJ, Checkley SA, English J, et al. Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers. Psychopharmacology (Berl). 2004;177:200–206
  52. Park SW, Lomri N, Simeoni LA, Fruehauf JP, Mechetner E. Analysis of P-glycoprotein-mediated membrane transport in human peripheral blood lymphocytes using the UIC2 shift assay. Cytometry A. 2003;53:67–78
  53. Penuelas I, Encio IJ, Lopez-Moratalla N, Santiago E. cAMP activates transcription of the human glucocorticoid receptor gene promoter. J. Steroid Biochem. Mol. Biol. 1998;67:89–94
  54. Piletz JE, Halaris A, Iqbal O, Hoppensteadt D, Fareed J, Zhu H, et al. Pro-inflammatory biomakers in depression: treatment with venlafaxine. World J. Biol. Psychiatry. 2008;1–11
  55. Rangarajan PN, Umesono K, Evans RM. Modulation of glucocorticoid receptor function by protein kinase A. Mol. Endocrinol. 1992;6:1451–1457
  56. Rohleder N, Schommer NC, Hellhammer DH, Engel R, Kirschbaum C. Sex differences in glucocorticoid sensitivity of proinflammatory cytokine production after psychosocial stress. Psychosom. Med. 2001;63:966–972
  57. Rohleder N, Wolf JM, Kirschbaum C. Glucocorticoid sensitivity in humans-interindividual differences and acute stress effects. Stress. 2003;6:207–222
  58. Roumestan C, Michel A, Bichon F, Portet K, Detoc M, Henriquet C, et al. Anti-inflammatory properties of desipramine and fluoxetine. Respir. Res. 2007;8:35
  59. Sunshine I, Baeumler J. A fatal case of poisoning with amitriptyline. Nature. 1963;199:1103–1104
  60. Taler M, Gil-Ad I, Lomnitski L, Korov I, Baharav E, Bar M, et al. Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur. Neuropsychopharmacol. 2007;17:774–780
  61. Thome J, Sakai N, Shin K, Steffen C, Zhang YJ, Impey S, et al. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J. Neurosci. 2000;20:4030–4036
  62. Toki S, Donati RJ, Rasenick MM. Treatment of C6 glioma cells and rats with antidepressant drugs increases the detergent extraction of G(s alpha) from plasma membrane. J. Neurochem. 1999;73:1114–1120
  63. Yau JL, Noble J, Hibberd C, Seckl JR. Short-term administration of fluoxetine and venlafaxine decreases corticosteroid receptor mRNA expression in the rat hippocampus. Neurosci. Lett. 2001;306:161–164

PII: S0924-977X(10)00039-8

doi: 10.1016/j.euroneuro.2010.02.006

European Neuropsychopharmacology
Volume 20, Issue 6 , Pages 379-387 , June 2010