Skip to main content

Advertisement

SpringerLink
Log in

Innovative Approaches for the Treatment of Depression: Targeting the HPA Axis

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Altered activity of the hypothalamic pituitary adrenal (HPA) axis is one of the most commonly observed neuroendocrine abnormalities in patients suffering from major depressive disorder (MDD). Altered cortisol secretion can be found in as many as 80% of depressed patients. This observation has led to intensive clinical and preclinical research aiming to better understand the molecular mechanisms which underlie the alteration of the HPA axis responsiveness in depressive illness. Dysfunctional glucocorticoid receptor (GR) mediated negative feedback regulation of cortisol levels and changes in arginine vasopressin (AVP)/vasopressin V1b receptor and corticotrophin-releasing factor/CRF1 receptor regulation of adrenocotricotrophin (ACTH) release have all been implicated in over-activity of the HPA axis. Agents that intervene with the mechanisms involved in (dys)regulation of cortisol synthesis and release are under investigation as possible therapeutic agents. The current status of some of these approaches is described in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:617–627

    Article  PubMed  Google Scholar 

  2. Fava M (2003) Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 53:649–659

    Article  PubMed  Google Scholar 

  3. Schatzberg AF, Rothschild AJ, Langlais PJ, Langlais PJ, Bird ED, Cole JO (1985) A corticosteroid/dopamine hypothesis for psychotic depression and related states. J Psychiatr Res 19:57–64

    Article  PubMed  CAS  Google Scholar 

  4. Putignano P, Dubini A, Toja P, Invitti C, Bonfanti S, Redaelli G, Zappulli D, Cavagnini F (2001) Salivary cortisol measurement in normal-weight, obese and anorexic women: comparison with plasma cortisol. Eur J Endocrinol 145:165–171

    Article  PubMed  CAS  Google Scholar 

  5. Marshall RD, Blanco C, Printz D, Liebowitz MR, Klein DF, Coplan J (2002) A pilot study of noradrenergic and HPA axis functioning in PTSD vs. panic disorder Psychiatry Res 110:219–230

    Article  PubMed  CAS  Google Scholar 

  6. Zobel AW, Nickel T, Sonntag A, Uhr M, Holsboer F, Ising M (2001) Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression. A prospective study. J Psychiatr Res 35:83–94

    Article  PubMed  CAS  Google Scholar 

  7. Zobel AW, Yassouridis A, Frieboes RM, Holsboer F (1999) Prediction of medium-term outcome by cortisol response to the combined dexamethasone-CRH test in patients with remitted depression. Am J Psychiatry 156:949–951

    PubMed  CAS  Google Scholar 

  8. Antoni FA, Holmes MC, Makara GB, Karteszi M, Laszlo FA (1984) Evidence that the effects of arginine-8-vasopressin (AVP) on pituitary corticotropin (ACTH) release are mediated by a novel type of receptor. Peptides 5:519–522

    Article  PubMed  CAS  Google Scholar 

  9. Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397

    Article  PubMed  CAS  Google Scholar 

  10. Karl HJ, Raith L (1966) Corticosterone secretion in humans. 3. Secretory rate of corticosterone and cortisol during stimulation of the adrenal cortex with ACTH. Klin Wochenschr 44:303–306

    Article  PubMed  CAS  Google Scholar 

  11. Munck A, Guyre PM, Holbrook NJ (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5:25–44

    Article  PubMed  CAS  Google Scholar 

  12. Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21:55–89

    Article  PubMed  CAS  Google Scholar 

  13. Erickson K, Drevets W, Schulkin J (2003) Glucocorticoid regulation of diverse cognitive functions in normal and pathological emotional states. Neurosci Biobehav Rev 27:233–246

    Article  PubMed  CAS  Google Scholar 

  14. Reul JM, de Kloet ER (1985) Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 117:2505–2511

    Article  PubMed  CAS  Google Scholar 

  15. Spencer RL, Young EA, Choo PH, McEwen BS (1990) Adrenal steroid type I. and type II receptor binding: estimates of in vivo receptor number, occupancy, and activation with varying level of steroid. Brain Res 514:37–48

    Article  PubMed  CAS  Google Scholar 

  16. de Kloet ER, Rots NY, Van den Berg DT, Oitzl MS (1994) Brain mineralocorticoid receptor function. Ann NY Acad Sci 746:8–20

    Article  PubMed  Google Scholar 

  17. Holsboer F, Barden N (1996) Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocr Rev 17:187–205

    PubMed  CAS  Google Scholar 

  18. Gold PW, Goodwin FK, Chrousos GP (1988) Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (1). N Engl J Med 319:348–353

    Article  PubMed  CAS  Google Scholar 

  19. Gold PW, Goodwin FK, Chrousos GP (1988) Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (2). N Engl J Med 319:413–420

    Article  PubMed  CAS  Google Scholar 

  20. Post RM (1992) Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 149:999–1010

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  22. Gold PW, Loriaux DL, Roy A, Kling MA, Calabrese JR, Kellner CH, Nieman LK, Post RM, Pickar D, Gallucci W (1986) Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing’s disease. Pathophysiologic and diagnostic implications. N Engl J Med 314:1329–1335

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  25. Holsboer F, Von Bardeleben U, Gerken A, Stalla GK, Muller OA (1984) Blunted corticotropin and normal cortisol response to human corticotropin-releasing factor in depression. N Engl J Med 311:1127

    PubMed  CAS  Google Scholar 

  26. Nemeroff CB, Widerlov E, Bissette G. Walleus H, Karlsson I, Eklund K, Kilts CD, Loosen PT, Vale W (1984) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226:1342–1344

    Article  PubMed  CAS  Google Scholar 

  27. Young EA, Kotun J, Haskett RF, Grunhaus L, Greden JF, Watson SJ, Akil H (1993) Dissociation between pituitary and adrenal suppression to dexamethasone in depression. Arch Gen Psychiatry 50:395–403

    PubMed  CAS  Google Scholar 

  28. Kathol RG, Anton R, Noyes R, Gehris T (1989) Direct comparison of urinary free cortisol excretion in patients with depression and panic disorder. Biol Psychiatry 25:873–878

    Article  PubMed  CAS  Google Scholar 

  29. Deuschle M, Schweiger U, Weber C, Gotthardt U, Korner A, Schmider J, Standhardt H, Lammers CH, Heuser I (1997) Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls. J Clin Endocrinol Metab 82:234–238

    Article  PubMed  CAS  Google Scholar 

  30. Amsterdam JD, Maislin G, Winokur A, Kling M, Gold P (1987) Pituitary and adrenocortical responses to the ovine corticotropin releasing hormone in depressed patients and healthy volunteers. Arch Gen Psychiatry 44:775–781

    PubMed  CAS  Google Scholar 

  31. Dinan TG, O’Brien S, Lavelle E, Scott LV (2004) Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in melancholic depression. Psychol Med 34:169–172

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  33. Abelson JL, Curtis GC (1996) Hypothalamic-pituitary-adrenal axis activity in panic disorder. 24-hour secretion of corticotropin and cortisol. Arch Gen Psychiatry 53:323–331

    PubMed  CAS  Google Scholar 

  34. Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, Southwick SM, Nemeroff CB, Charney DS (1997) Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. Am J Psychiatry 154:624–629

    PubMed  CAS  Google Scholar 

  35. de Kloet CS, Vermettenm E, Geuze E, Kavelaars A, Heijnen CJ, Westenberg HG (2006) Assessment of HPA-axis function in posttraumatic stress disorder: pharmacological and non-pharmacological challenge tests, a review. J Psychiatr Res 40:550–567

    Article  PubMed  Google Scholar 

  36. Carroll BJ, Feinberg M, Greden JF, Tarika J, Albala AA, Haskett RF, James NM, Kronfol Z, Lohr N, Steiner M, de Vigne JP, Young E (1981) A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry 38:15–22

    PubMed  CAS  Google Scholar 

  37. Holsboer F, Von Bardeleben U, Wiedemann K, Muller OA, Stalla GK (1987) Serial assessment of corticotropin-releasing hormone response after dexamethasone in depression. Implications for pathophysiology of DST nonsuppression. Biol Psychiatry 22:228–234

    Article  PubMed  CAS  Google Scholar 

  38. Von Bardeleben U, Holsboer F (1991) Effect of age on the cortisol response to human corticotropin-releasing hormone in depressed patients pretreated with dexamethasone. Biol Psychiatry 29:1042–1050

    Article  Google Scholar 

  39. Heuser I, Yassouridis A, Holsboer F (1994) The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res 28:341–356

    Article  PubMed  CAS  Google Scholar 

  40. Modell S, Yassouridis A, Huber J, Holsboer F (1997) Corticosteroid receptor function is decreased in depressed patients. Neuroendocrinology 65:216–222

    Article  PubMed  CAS  Google Scholar 

  41. Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W, Zink M, Hortnagl H, Flor H, Henn FA, Schutz G, Gass P (2005) Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 25:6243–6250

    Article  PubMed  CAS  Google Scholar 

  42. Reul JM, Stec I, Soder M, Holsboer F (1993) Chronic treatment of rats with the antidepressant amitriptyline attenuates the activity of the hypothalamic-pituitary-adrenocortical system. Endocrinology 133:312–320

    Article  PubMed  CAS  Google Scholar 

  43. Reul JM, Labeur MS, Grigoriadis DE, De Souza EB, Holsboer F (1994) Hypothalamic-pituitary-adrenocortical axis changes in the rat after long-term treatment with the reversible monoamine oxidase-A inhibitor moclobemide. Neuroendocrinology 60:509–519

    Article  PubMed  CAS  Google Scholar 

  44. Kitayama I, Janson AM, Cintra A, Fuxe K, Agnati LF, Ogren SO, Harfstrand A, Eneroth P, Gustafsson JA (1988) Effects of chronic imipramine treatment on glucocorticoid receptor immunoreactivity in various regions of the rat brain. Evidence for selective increases of glucocorticoid receptor immunoreactivity in the locus coeruleus and in 5-hydroxytryptamine nerve cell groups of the rostral ventromedial medulla. J Neural Transm 73:191–203

    Article  PubMed  CAS  Google Scholar 

  45. Seckl JR, Fink G (1992) Antidepressants increase glucocorticoid and mineralocorticoid receptor mRNA expression in rat hippocampus in vivo. Neuroendocrinology 55:621–626

    Article  PubMed  CAS  Google Scholar 

  46. Pepin MC, Beaulieu S, Barden N (1989) Antidepressants regulate glucocorticoid receptor messenger RNA concentrations in primary neuronal cultures. Brain Res Mol Brain Res 6:77–83

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  48. Altemus M, Pigott T, Kalogeras KT, Demitrack M, Dubbert B, Murphy DL, Gold PW (1992) Abnormalities in the regulation of vasopressin and corticotropin releasing factor secretion in obsessive-compulsive disorder. Arch Gen Psychiatry 49:9–20

    PubMed  CAS  Google Scholar 

  49. Geracioti TD Jr, Loosen PT, Orth DN (1997) Low cerebrospinal fluid corticotropin-releasing hormone concentrations in eucortisolemic depression. Biol Psychiatry 42:165–174

    Article  PubMed  CAS  Google Scholar 

  50. Kling MA, Roy A, Doran AR, Calabrese JR, Rubinow DR, Whitfield HJ Jr, May C, Post RM, Chrousos GP, Gold PW (1991) Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing’s. disease and major depression: potential clinical implications. J Clin Endocrinol Metab 72:260–271

    Article  PubMed  CAS  Google Scholar 

  51. Pitts AF, Samuelson SD, Meller WH, Bissette G, Nemeroff CB, Kathol RG (1995) Cerebrospinal fluid corticotropin-releasing hormone, vasopressin, and oxytocin concentrations in treated patients with major depression and controls. Biol Psychiatry 38:330–335

    Article  PubMed  CAS  Google Scholar 

  52. Holsboer F (1999) The rationale for corticotropin-releasing hormone receptor (CRH-R.) antagonists to treat depression and anxiety. J Psychiatr Res 33:181–214

    Article  PubMed  CAS  Google Scholar 

  53. Nemeroff CB, Owens MJ, Bissette G, Andorn AC, Stanley M (1988) Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 45:577–579

    PubMed  CAS  Google Scholar 

  54. Rupprecht R, Lesch KP, Muller U, Beck G, Beckmann H, Schulte HM (1989) Blunted adrenocorticotropin but normal beta-endorphin release after human corticotropin-releasing hormone administration in depression. J Clin Endocrinol Metab 69:600–603

    Article  PubMed  CAS  Google Scholar 

  55. Altemus M, Swedo SE, Leonard HL, Richter D, Rubinow DR, Potter WZ, Rapoport JL (1994) Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine. Arch Gen Psychiatry 51:794–803

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  59. Brady LS, Gold PW, Herkenham M, Lynn AB, Whitfield HJ Jr (1992) The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications. Brain Res 572:117–125

    Article  PubMed  CAS  Google Scholar 

  60. Brady LS, Whitfield HJ Jr, Fox RJ, Gold PW, Herkenham M (1991) Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications. J Clin Invest 87:831–837

    Article  PubMed  CAS  Google Scholar 

  61. Jensen JB, Jessop DS, Harbuz MS, Harbuz MS, Mork A, Sanchez C, Mikkelsen JD (1999) Acute and long-term treatments with the selective serotonin reuptake inhibitor citalopram modulate the HPA axis activity at different levels in male rats. J Neuroendocrinol 11:465–471

    Article  PubMed  CAS  Google Scholar 

  62. Stout SC, Owens MJ, Nemeroff CB (2002) Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment. J Pharmacol Exp Ther 300:1085–1092

    Article  PubMed  CAS  Google Scholar 

  63. Grigoriadis DE, Pearsall D, De Souza EB (1989) Effects of chronic antidepressant and benzodiazepine treatment on corticotropin-releasing-factor receptors in rat brain and pituitary. Neuropsychopharmacology 2:53–60

    Article  PubMed  CAS  Google Scholar 

  64. van Praag HM (2004) Let the facts prevail. World J Biol Psychiatry 5:116

    Article  PubMed  Google Scholar 

  65. Zorrilla EP, Valdez GR, Nozulak J, Koob GF, Markou A (2002) Effects of antalarmin, a CRF type 1 receptor antagonist, on anxiety-like behavior and motor activation in the rat. Brain Res 952:188–199

    Article  PubMed  CAS  Google Scholar 

  66. Song C, Earley C, Leonard BE (1995) Behavioral, neurochemical, and immunological responses to CRF administration. Is CRF a mediator of stress? Ann NY Acad Sci 771:55–72

    Article  PubMed  CAS  Google Scholar 

  67. Jones DN, Kortekaas R, Slade PD, Middlemiss DN, Hagan JJ (1998) The behavioural effects of corticotropin-releasing factor-related peptides in rats. Psychopharmacology 138:124–132

    Article  PubMed  CAS  Google Scholar 

  68. Stenzel-Poore MP, Heinrichs SC, Rivest S, Koob GF, Vale WW (1994) Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior. J Neurosci 14:2579–2584

    PubMed  CAS  Google Scholar 

  69. Heinrichs SC, Min H, Tamraz S, Carmouche M, Boehme SA, Vale WW (1997) Anti-sexual and anxiogenic behavioral consequences of corticotropin-releasing factor overexpression are centrally mediated. Psychoneuroendocrinology 22:215–224

    Article  PubMed  CAS  Google Scholar 

  70. van Gaalen MM, Stenzel-Poore MP, Holsboer F, Steckler T (2002) Effects of transgenic overproduction of CRH on anxiety-like behaviour. Eur J Neurosci 15:2007–2015

    Article  PubMed  Google Scholar 

  71. Liebsch G, Landgraf R, Gerstberger R, Probst JC, Wotjak CT, Engelmann M, Holsboer F, Montkowski A (1995) Chronic infusion of a CRH1 receptor antisense oligodeoxynucleotide into the central nucleus of the amygdala reduced anxiety-related behavior in socially defeated rats. Regul Pept 59:229–239

    Article  PubMed  CAS  Google Scholar 

  72. Smith GW, Aubry JM, Dellu F, Contarino A, Bilezikjian LM, Gold LH, Chen R, Marchuk Y, Hauser C, Bentley CA, Sawchenko PE, Koob GF, Vale W, Lee KF (1998) Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron 20:1093–1102

    Article  PubMed  CAS  Google Scholar 

  73. Timpl P, Spanagel R, Sillaber I. Kresse A, Reul JM, Stalla GK, Blanquet V, Steckler T, Holsboer F, Wurst W (1998) Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor. Nat Genet 19:162–166

    Article  PubMed  CAS  Google Scholar 

  74. Muller MB, Zimmermann S, Sillaber I, Hagemeyer TP, Deussing JM, Timpl P, Kormann MS, Droste SK, Kuhn R, Reul JM, Holsboer F, Wurst W (2003) Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress. Nat Neurosci 6:1100–1107

    Article  PubMed  CAS  Google Scholar 

  75. Purba JS, Hoogendijk WJ, Hofman MA, Swaab DF (1996) Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 53:137–143

    PubMed  CAS  Google Scholar 

  76. Zhou JN, Riemersma RF, Unmehopam UA Hoogendijk WJ, van Heerikhuize JJ, Hofman MA, Swaab DF (2001) Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression. Arch Gen Psychiatry 58:655–662

    Article  PubMed  CAS  Google Scholar 

  77. de Winter RF, van Hemert AM, DeRijk RH, Zwinderman KH, Frankhuijzen-Sierevogel AC, Wiegant VM, Goekoop JG (2003) Anxious-retarded depression: relation with plasma vasopressin and cortisol. Neuropsychopharmacology 28:140–147

    Article  PubMed  CAS  Google Scholar 

  78. van Londen L, Goekoop JG, van Kempen GM, Frankhuijzen-Sierevogel AC, Wiegant VM, van der Velde EA, De Wied D (1997) Plasma levels of arginine vasopressin elevated in patients with major depression. Neuropsychopharmacology 17:284–292

    Article  PubMed  Google Scholar 

  79. Brunner J, Keck ME, Landgraf R, Uhr M, Namendorf C, Bronisch T (2002) Vasopressin in CSF and plasma in depressed suicide attempters: preliminary results. Eur Neuropsychopharmacology 12:489–494

    Article  CAS  Google Scholar 

  80. Sorensen PS, Gjerris A, Hammer M (1985) Cerebrospinal fluid vasopressin in neurological and psychiatric disorders. J Neurol Neurosurg Psychiatry 48:50–57

    Article  PubMed  CAS  Google Scholar 

  81. Gjerris A, Hammer M, Vendsborg P, Christensen NJ, Rafaelsen OJ (1985) Cerebrospinal fluid vasopressin-changes in depression. Br J Psychiatry 147:696–701

    Article  PubMed  CAS  Google Scholar 

  82. Abelson JL, Le Melledo J, Bichet DG (2001) Dose response of arginine vasopressin to the CCK-C agonist pentagastrin. Neuropsychopharmacology 24:161–169

    Article  PubMed  CAS  Google Scholar 

  83. Carroll BJ (1972) Stimulation tests in depression. In: Davies B, Carroll BJ, Mowbray RM (eds) Depressive illness: some research studies. CC Thomas, Springfield, pp 151–153

    Google Scholar 

  84. Krahn DD, Meller WH, Shafer RB, Morley JE (1985) Cortisol response to vasopressin in depression. Biol Psychiatry 20:918–921

    Article  PubMed  CAS  Google Scholar 

  85. Dinan TG, Lavelle E, Scott LV, Newell-Price J, Medbak S, Grossman AB (1999) Desmopressin normalizes the blunted adrenocorticotropin response to corticotropin-releasing hormone in melancholic depression: evidence of enhanced vasopressinergic responsivity. J Clin Endocrinol Metab 84:2238–2240

    Article  PubMed  CAS  Google Scholar 

  86. Whitnall MH, Smyth D, Gainer H (1987) Vasopressin coexists in half of the corticotropin-releasing factor axons present in the external zone of the median eminence in normal rats. Neuroendocrinology 45:420–424

    Article  PubMed  CAS  Google Scholar 

  87. Rabadan-Diehl C, Lolait SJ, Aguilera G (1995) Regulation of pituitary vasopressin V1b receptor mRNA during stress in the rat. J Neuroendocrinol 7:903–910

    Article  PubMed  CAS  Google Scholar 

  88. Whitnall MH (1989) Stress selectively activates the vasopressin-containing subset of corticotropin-releasing hormone neurons. Neuroendocrinology 50:702–707

    Article  PubMed  CAS  Google Scholar 

  89. Abou-Samra AB, Catt KJ, Aguilera G (1986) Biphasic inhibition of adrenocorticotropin release by corticosterone in cultured anterior pituitary cells. Endocrinology 119:972–977

    Article  PubMed  CAS  Google Scholar 

  90. Bilezikjian LM, Blount AL, Vale WW (1987) The cellular actions of vasopressin on corticotrophs of the anterior pituitary: resistance to glucocorticoid action. Mol Endocrinol 1:451–458

    Article  PubMed  CAS  Google Scholar 

  91. Keck ME, Wigger A, Welt T, Muller MB, Gesing A, Reul JM, Holsboer F, Landgraf R, Neumann ID (2002) Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders. Neuropsychopharmacology 26:94–105

    Article  PubMed  CAS  Google Scholar 

  92. Landgraf R, Wigger A, Holsboer F, Neumann ID (1999) Hyper-reactive hypothalamo-pituitary-adrenocortical axis in rats bred for high anxiety-related behaviour. J Neuroendocrinol 11:405–407

    Article  PubMed  CAS  Google Scholar 

  93. Salome N, Stemmelin J, Cohen C, Griebel G (2006) Differential roles of amygdaloid nuclei in the anxiolytic- and antidepressant-like effects of the V1b receptor antagonist, SSR149415, in rats. Psychopharmacology 187:237–244

    Article  PubMed  CAS  Google Scholar 

  94. Murgatroyd C, Wigger A, Frank E, Singewald N, Bunck M, Holsboer F, Landgraf R, Spengler D (2004) Impaired repression at a vasopressin promoter polymorphism underlies overexpression of vasopressin in a rat model of trait anxiety. J Neurosci 24:7762–7770

    Article  PubMed  CAS  Google Scholar 

  95. Wigger A, Sanchez MM, Mathys KC, Ebner K, Frank E, Liu D, Kresse A, Neumann ID, Holsboer F, Plotsky PM, Landgraf R (2004) Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety: critical role of vasopressin. Neuropsychopharmacology 29:1–14

    Article  PubMed  CAS  Google Scholar 

  96. Keck ME, Welt T, Muller MB, Uhr M, Ohl F, Wigger A, Toschi N, Holsboer F, Landgraf R (2003) Reduction of hypothalamic vasopressinergic hyperdrive contributes to clinically relevant behavioral and neuroendocrine effects of chronic paroxetine treatment in a psychopathological rat model. Neuropsychopharmacology 28:235–243

    Article  PubMed  CAS  Google Scholar 

  97. Landgraf R (2006) The involvement of the vasopressin system in stress-related disorders. CNS Neurol Disord Drug Targets 5:167–179

    Article  PubMed  CAS  Google Scholar 

  98. Caffe AR, van Leeuwen FW, Luiten PG (1987) Vasopressin cells in the medial amygdala of the rat project to the lateral septum and ventral hippocampus. J Comp Neurol 261:237–252

    Article  PubMed  CAS  Google Scholar 

  99. De Vries GJ, Buijs RM (1983) The origin of the vasopressinergic and oxytocinergic innervation of the rat brain with special reference to the lateral septum. Brain Res 273:307–317

    Article  PubMed  Google Scholar 

  100. Wotjak CT, Kubota M, Liebsch G, Montkowski A, Holsboer F, Neumann I, Landgraf R (1996) Release of vasopressin within the rat paraventricular nucleus in response to emotional stress: a novel mechanism of regulating adrenocorticotropic hormone secretion?. J Neurosci 16:7725–7732

    PubMed  CAS  Google Scholar 

  101. Ebner K, Wotjak CT, Landgraf R, Engelmann M (2000) A single social defeat experience selectively stimulates the release of oxytocin, but not vasopressin, within the septal brain area of male rats. Brain Res 872:87–92

    Article  PubMed  CAS  Google Scholar 

  102. Ebner K, Wotjak CT, Holsboer F, Engelmann M (1999) Vasopressin released within the septal brain area during swim stress modulates the behavioural stress response in rats. Eur J Neurosci 11:997–1002

    Article  PubMed  CAS  Google Scholar 

  103. Wotjak CT, Ganster J, Kohl G, Holsboer F, Landgraf R, Engelmann M (1998) Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: new insights into the secretory capacities of peptidergic neurons. Neuroscience 85:1209–1222

    Article  PubMed  CAS  Google Scholar 

  104. Hernando F, Schoots O, Lolait SJ, Burbach JP (2001) Immunohistochemical localization of the vasopressin V1b receptor in the rat brain and pituitary gland: anatomical support for its involvement in the central effects of vasopressin. Endocrinology 142:1659–1668

    Article  PubMed  CAS  Google Scholar 

  105. Young WS, Li J, Wersinger SR, Palkovits M (2006) The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy. Neuroscience 143:1031–1039

    Article  PubMed  CAS  Google Scholar 

  106. Wersinger SR, Ginns EI, O’Carroll AM, Lolait SJ, Young WS III (2002) Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol Psychiatry 7:975–984

    Article  PubMed  CAS  Google Scholar 

  107. Itoh S, Yamada S, Mori T, Miwa T, Tottori K, Uwahodo Y, Yamamura Y, Fukuda M, Yamamoto K, Tanoue A, Tsujimoto G (2006) Attenuated stress-induced catecholamine release in mice lacking the vasopressin V1b receptor. Am J Physiol Endocrinol Metab 291:E147–E151

    Article  PubMed  CAS  Google Scholar 

  108. Wersinger SR, Kelliher KR, Zufall F, Lolait SJ, O’Carroll AM, Young WS III (2004) Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task. Horm Behav 46:638–645

    Article  PubMed  CAS  Google Scholar 

  109. Tanoue A, Ito S, Honda K, Oshikawa S, Kitagawa Y, Koshimizu TA, Mori T, Tsujimoto G (2004) The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J Clin Invest 113:302–309

    PubMed  CAS  Google Scholar 

  110. Lolait SJ, Stewart LQ, Jessop DS, Young WS III, O’Carroll AM (2007) The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin V1b receptors. Endocrinology 148:849–856

    Article  PubMed  CAS  Google Scholar 

  111. Het S, Ramlow G, Wolf OT (2005) A meta-analytic review of the effects of acute cortisol administration on human memory. Psychoneuroendocrinology 30:771–784

    Article  PubMed  CAS  Google Scholar 

  112. Roozendaal C (2002) Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval. Neurobiol Learn Mem 78:578–595

    Article  PubMed  CAS  Google Scholar 

  113. Starkman MN, Giordani C, Berent S, Schork MA, Schteingart DE (2001) Elevated cortisol levels in Cushing’s. disease are associated with cognitive decrements. Psychosom Med 63:985–993

    PubMed  CAS  Google Scholar 

  114. Sonino N, Fava GA (2001) Psychiatric disorders associated with Cushing’s. syndrome. Epidemiology, pathophysiology and treatment. CNS Drugs 15:361–373

    Article  PubMed  CAS  Google Scholar 

  115. Dorn LD, Burgess ES, Friedman TC, Dubbert B, Gold PW, Chrousos GP (1997) The longitudinal course of psychopathology in Cushing’s. syndrome after correction of hypercortisolism. J Clin Endocrinol Metab 82:912–919

    Article  PubMed  CAS  Google Scholar 

  116. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW (1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93:3908–3913

    Article  PubMed  CAS  Google Scholar 

  117. Starkman MN, Gebarski SS, Berent S et al (1992) Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing’s. syndrome. Biol Psychiatry 32(9):756–765

    Article  PubMed  CAS  Google Scholar 

  118. Starkman MN, Giordani C, Gebarski SS, Berent S, Schork MA, Schteingart DE (1999) Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing’s. disease. Biol Psychiatry 46:1595–1602

    Article  PubMed  CAS  Google Scholar 

  119. Gould E, Tanapat P (1999) Stress and hippocampal neurogenesis. Biol Psychiatry 46:1472–1479

    Article  PubMed  CAS  Google Scholar 

  120. Sousa N, Madeira MD, Paula-Barbosa MM (1998) Effects of corticosterone treatment and rehabilitation on the hippocampal formation of neonatal and adult rats. An unbiased stereological study. Brain Res 794:199–210

    Article  PubMed  CAS  Google Scholar 

  121. Chen H, Pandey GN, Dwivedi Y (2006) Hippocampal cell proliferation regulation by repeated stress and antidepressants. Neuroreport 17:863–867

    Article  PubMed  Google Scholar 

  122. Fuchs E, Flugge G, Ohl F, Lucassen P, Vollmann-Honsdorf GK, Michaelis T (2001) Psychosocial stress, glucocorticoids, and structural alterations in the tree shrew hippocampus. Physiol Behav 73:285–291

    Article  PubMed  CAS  Google Scholar 

  123. Montaron MF, Drapeau E, Dupret D, Kitchener P, Aurousseau C, Le Moal M, Piazza PV, Abrous DN (2006) Lifelong corticosterone level determines age-related decline in neurogenesis and memory. Neurobiol Aging 27:645–654

    Article  PubMed  CAS  Google Scholar 

  124. Crochemore C, Lu J, Wu Y, Liposits Z, Sousa N, Holsboer F, Almeida OF (2005) Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation. Mol Psychiatry 10:790–798

    Article  PubMed  CAS  Google Scholar 

  125. Pariante CM, Thomas SA, Lovestone S, Makoof A, Kerwin RW (2004) Do antidpressants regulate how cortisol affects the brain? Psychoneuroendocrinology 29:423–447

    Article  PubMed  CAS  Google Scholar 

  126. Karssen AM, Meijer OC, van der Sandt IC, Lucassen PJ, de Lange EC, de Boer AG, de Kloet ER (2001) Multidrug resistance P-glycoprotein hampers the access of cortisol but not of corticosterone to mouse and human brain. Endocrinology 142:2686–2694

    Article  PubMed  CAS  Google Scholar 

  127. Schinkel AH (1999) P-Glycoprotein, a gatekeeper in the blood–brain barrier. Adv Drug Deliv Rev 36:179–194

    Article  PubMed  CAS  Google Scholar 

  128. Pariante CM, Kim RB, Makoff A, Kerwin RW (2003) Antidepressant fluoxetine enhances glucocorticoid receptor function in vitro by modulating membrane steroid transporters. Br J Pharmacol 139:1111–1118

    Article  PubMed  CAS  Google Scholar 

  129. Pariante CM, Hye A, Williamson R, Makoff A, Lovestone S, Kerwin RW (2003) The antidepressant clomipramine regulates cortisol intracellular concentrations and glucocorticoid receptor expression in fibroblasts and rat primary neurones. Neuropsychopharmacology 28:1553–1561

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  131. Murphy BE (1997) Antiglucocorticoid therapies in major depression: a review. Psychoneuroendocrinology 22:S125–S132

    Article  PubMed  Google Scholar 

  132. Murphy BE (1991) Treatment of major depression with steroid suppressive drugs. J Steroid Biochem Mol Biol 39:239–244

    Article  PubMed  CAS  Google Scholar 

  133. Murphy BE, Ghadirian AM, Dhar V (1998) Neuroendocrine responses to inhibitors of steroid biosynthesis in patients with major depression resistant to antidepressant therapy. Can J Psychiatry 43:279–286

    PubMed  CAS  Google Scholar 

  134. O’Dwyer AM, Lightman SL, Marks MN, Checkley SA (1995) Treatment of major depression with metyrapone and hydrocortisone. J Affect Disord 33:123–128

    Article  PubMed  CAS  Google Scholar 

  135. Thakore JH, Dinan TG (1995) Cortisol synthesis inhibition: a new treatment strategy for the clinical and endocrine manifestations of depression. Biol Psychiatry 37:364–368

    Article  PubMed  CAS  Google Scholar 

  136. Wolkowitz OM, Reus VI, Manfredi F, Ingbar J, Brizendine L, Weingartner H (1993) Ketoconazole administration in hypercortisolemic depression. Am J Psychiatry 150:810–812

    PubMed  CAS  Google Scholar 

  137. Cohen H, Benjamin J, Kaplan Z, Kotler M (2000) Administration of high-dose ketoconazole, an inhibitor of steroid synthesis, prevents posttraumatic anxiety in an animal model. Eur Neuropsychopharmacol 10:429–435

    Article  PubMed  CAS  Google Scholar 

  138. Kennett GA, Dickinson SL, Curzon G (1985) Central serotonergic responses and behavioural adaptation to repeated immobilisation: the effect of the corticosterone synthesis inhibitor metyrapone. Eur J Pharmacol 119:143–152

    Article  PubMed  CAS  Google Scholar 

  139. Rogoz Z, Budziszewska C, Kubera M, Basta-Kaim A, Jaworska-Feil L, Skuza G, Lason W (2005) Effect of combined treatment with imipramine and metyrapone on the immobility time, the activity of hypothalamo-pituitary-adrenocortical axis and immunological parameters in the forced swimming test in the rat. J Physiol Pharmacol 56:49–61

    PubMed  CAS  Google Scholar 

  140. Jahn H, Schick M, Kiefer F, Kellner M, Yassouridis A, Wiedemann K (2004) Metyrapone as additive treatment in major depression: a double-blind and placebo-controlled trial. Arch Gen Psychiatry 61:1235–1244

    Article  PubMed  CAS  Google Scholar 

  141. White PC, Speiser PW (1994) Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am 23:325–339

    PubMed  CAS  Google Scholar 

  142. Craighead M, Macdonald S, Hilier A, Speake M, Thomson F, Turnbull Z, Watson L (2004) Org 34850 is a potent antagonist of the glucorticoid receptor, in vivo and in vitro. J Affect Disord 78:S107

    Google Scholar 

  143. Thomson F, Broekkamp C, Craighead M, Eason S, Hilier A, Peeters C, Speake M, Watson L (2004) In vivo and in vitro charterisation of the glucocorticoid receptor antagonist Org 34517. J Affect Disord 78:S138

    Google Scholar 

  144. Mayer JL, Klumpers L, Maslam S, de Kloet ER, Joels M, Lucassen PJ (2006) Brief treatment with the glucocorticoid receptor antagonist mifepristone normalises the corticosterone-induced reduction of adult hippocampal neurogenesis. J Neuroendocrinol 18:629–631

    Article  PubMed  CAS  Google Scholar 

  145. Spiga F, Harrison LR, Wood SA, Atkinson HC, MacSweeney C, Lightman SL (2006) Sub-chronic treatment with the glucocorticoid receptor antagonist Org 34850 increases basal HPA axis activity in rats. ISPNE Congress 2006, Leiden, The Netherlands

  146. Bachmann CG, Linthorst AC, Holsboer F, Reul JM (2003) Effect of chronic administration of selective glucocorticoid receptor antagonists on the rat hypothalamic-pituitary-adrenocortical axis. Neuropsychopharmacology 28:1056–1067

    PubMed  CAS  Google Scholar 

  147. de Kloet ER, De Kock S, Schild V, Veldhuis HD (1988) Antiglucocorticoid RU 38486 attenuates retention of a behaviour and disinhibits the hypothalamic-pituitary adrenal axis at different brain sites. Neuroendocrinology 47:109–115

    Article  PubMed  Google Scholar 

  148. Bilang-Bleuel A, Ulbricht S, Chandramohan Y, De Carli S, Droste SK, Reul JM (2005) Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response. Eur J Neurosci 22:1691–1700

    Article  PubMed  Google Scholar 

  149. Smith LH, Erdemli G, Grassie M (2005) Central action of glucocorticoid receptor antagonists. ISPNE Congress 2005, Montreal, Canada

  150. Smith LH, Erdemli G, Grassie M (2005) Central action of glucocorticoid receptor antagonists. BAP Congress 2005, Harrogate, UK

  151. van der Lely AJ, Foeken K, van der Mast RC, Lamberts SW (1991) Rapid reversal of acute psychosis in the Cushing syndrome with the cortisol-receptor antagonist mifepristone (RU 486). Ann Intern Med 114:143–144

    PubMed  Google Scholar 

  152. Hoyberg OJ, Wijk G, Mehtonen OP, Peeters BWMM, Senneff C (2002) Org 34517, a selective glucocorticoid receptor antagonist with potent antidepressant activity: First clinical results. Int J Neuropsychopharmacol 5:S148

    Google Scholar 

  153. Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF (2001) Rapid reversal of psychotic depression using mifepristone. J Clin Psychopharmacol 21:516–521

    Article  PubMed  CAS  Google Scholar 

  154. DeBattista C, Belanoff J, Glass S, Khan A, Horne RL, Blasey C, Carpenter LL, Alva G (2006) Mifepristone versus placebo in the treatment of psychosis in patients with psychotic major depression. Biol Psychiatry 60:1343–1349

    Article  PubMed  CAS  Google Scholar 

  155. Young AH, Gallagher P, Watson S, Del Estal D, Owen BM, Ferrier IN (2004) Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder. Neuropsychopharmacology 29:1538–1545

    Article  PubMed  CAS  Google Scholar 

  156. Gallagher P, Watson S, Smith MS, Ferrier IN, Young AH (2005) Effects of adjunctive mifepristone (RU-486) administration on neurocognitive function and symptoms in schizophrenia. Biol Psychiatry 57:155–161

    Article  PubMed  CAS  Google Scholar 

  157. Laue L, Lotze MT, Chrousos GP, Barnes K, Loriaux DL, Fleisher TA (1990) Effect of chronic treatment with the glucocorticoid antagonist RU 486 in man: toxicity, immunological, and hormonal aspects J Clin Endocrinol Metab 71:1474–1480

    Article  PubMed  CAS  Google Scholar 

  158. Zorrilla EP, Koob GF (2004) The therapeutic potential of CRF1 antagonists for anxiety. Expert Opin Investig Drugs 13:799–828

    Article  PubMed  CAS  Google Scholar 

  159. Nielsen DM, Carey GJ, Gold LH (2004) Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in mice. Eur J Pharmacol 499:135–146

    Article  PubMed  CAS  Google Scholar 

  160. Alonso R, Griebel G, Pavone G, Stemmelin J, Le Fur G, Soubrie P (2004) Blockade of CRF(1) or V(1b) receptors reverses stress-induced suppression of neurogenesis in a mouse model of depression. Mol Psychiatry 9:278–286, 224

    Google Scholar 

  161. Keck ME, Welt T, Wigger A, Renner U, Engelmann M, Holsboer F, Landgraf R (2001) The anxiolytic effect of the CRH(1) receptor antagonist R121919 depends on innate emotionality in rats. Eur J Neurosci 13:373–380

    Article  PubMed  CAS  Google Scholar 

  162. Gutman DA, Owens MJ, Skelton KH, Thrivikraman KV, Nemeroff CB (2003) The corticotropin-releasing factor1 receptor antagonist R121919 attenuates the behavioral and endocrine responses to stress. J Pharmacol Exp Ther 304:874–880

    Article  PubMed  CAS  Google Scholar 

  163. Post A, Ohl F, Almeida OF, Binder EB, Rucker M, Welt S, Binder E, Holsboer F, Sillaber I (2005) Identification of molecules potentially involved in mediating the in vivo actions of the corticotropin-releasing hormone receptor 1 antagonist, NBI30775 (R121919). Psychopharmacology 180:150–158

    Article  PubMed  CAS  Google Scholar 

  164. Curtis AL, Lechner SM, Pavcovich LA, Valentino RJ (1997) Activation of the locus coeruleus noradrenergic system by intracoerulear microinfusion of corticotropin-releasing factor: effects on discharge rate, cortical norepinephrine levels and cortical electroencephalographic activity. J Pharmacol Exp Ther 281:163–172

    PubMed  CAS  Google Scholar 

  165. Lejeune F, Millan MJ (2003) The CRF1 receptor antagonist, DMP695, abolishes activation of locus coeruleus noradrenergic neurones by CRF in anesthetized rats. Eur J Pharmacol 464:127–133

    Article  PubMed  CAS  Google Scholar 

  166. Schulz DW, Mansbach RS, Sprouse J, Braselton JP, Collins J, Corman M, Dunaiskis A, Faraci S, Schmidt AW, Seeger T, Seymour P, Tingley FD III, Winston EN, Chen YL, Heym J (1996) CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors. Proc Natl Acad Sci USA 93:10477–10482

    Article  PubMed  CAS  Google Scholar 

  167. Oshima A, Flachskamm C, Reul JM, Holsboer F, Linthorst AC (2003) Altered serotonergic neurotransmission but normal hypothalamic-pituitary-adrenocortical axis activity in mice chronically treated with the corticotropin-releasing hormone receptor type 1 antagonist NBI 30775. Neuropsychopharmacology 28:2148–2159

    PubMed  CAS  Google Scholar 

  168. Zobel AW, Nickel T, Kunzel HE, Ackl N, Sonntag A, Ising M, Holsboer F (2000) Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res 34:171–181

    Article  PubMed  CAS  Google Scholar 

  169. Held K, Kunzel H, Ising M, Schmid DA, Zobel A, Murck H, Holsboer F, Steiger A (2004) Treatment with the CRH1-receptor-antagonist R121919 improves sleep-EEG in patients with depression. J Psychiatr Res 38:129–136

    Article  PubMed  CAS  Google Scholar 

  170. Kunzel HE, Ising M, Zobel AW, Nickel T, Ackl N, Sonntag A, Holsboer F, Uhr M (2005) Treatment with a CRH-1-receptor antagonist (R121919) does not affect weight or plasma leptin concentration in patients with major depression. J Psychiatr Res 39:173–177

    Article  PubMed  Google Scholar 

  171. Kunzel HE, Zobel AW, Nickel T, Ackl N, Uhr M, Sonntag A, Ising M, Holsboer F (2003) Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects. J Psychiatr Res 37:525–533

    Article  PubMed  Google Scholar 

  172. Griebel G, Simiand J, Stemmelin J, Gal CS, Steinberg R (2003) The vasopressin V1b receptor as a therapeutic target in stress-related disorders. Curr Drug Targets CNS Neurol Disord 2:191–200

    Article  PubMed  CAS  Google Scholar 

  173. Griffante C, Green A, Curcuruto O, Haslam CP, Dickinson BA, Arban R (2005) Selectivity of d[Cha4]AVP and SSR149415 at human vasopressin and oxytocin receptors: evidence that SSR149415 is a mixed vasopressin V1b/oxytocin receptor antagonist. Br J Pharmacol 146:744–751

    Article  PubMed  CAS  Google Scholar 

  174. Serradeil-Le Gal C, Wagnon J, Simiand J, Griebel G, Lacour C, Guillon G, Barberis C, Brossard G, Soubrie P, Nisato D, Pascal M, Pruss R, Scatton B, Maffrand JP, Le Fur G (2002) Characterization of (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N.,N.-dimethyl-2-pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b receptor antagonist. J Pharmacol Exp Ther 300:1122–1130

    Article  PubMed  CAS  Google Scholar 

  175. Griebel G, Simiand J, Steinberg R, Jung M, Gully D, Roger P, Geslin M, Scatton B, Maffrand JP, Soubrie P (2002) 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N.-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders. J Pharmacol Exp Ther 301:333–345

    Article  PubMed  CAS  Google Scholar 

  176. Shimazaki T, Iijima M, Chaki S (2006) The pituitary mediates the anxiolytic-like effects of the vasopressin V1b receptor antagonist, SSR149415, in a social interaction test in rats. Eur J Pharmacol 543:63–67

    Article  PubMed  CAS  Google Scholar 

  177. Stemmelin J, Lukovic L, Salome N, Griebel G (2005) Evidence that the lateral septum is involved in the antidepressant-like effects of the vasopressin V1b receptor antagonist, SSR149415. Neuropsychopharmacology 30(1):35–42

    Article  PubMed  CAS  Google Scholar 

  178. Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B, Maffrand JP, Soubrie P (2002) Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci USA 99:6370–6375

    Article  PubMed  CAS  Google Scholar 

  179. Carroll BJ (1982) Clinical applications of the dexamethasone supprssion test for endogenous depression. Pharmacopsychiatria 15:19–25

    Article  PubMed  CAS  Google Scholar 

  180. Kudielka BM, Buske-Kirschbaum A, Hellhammer DH, Kirschbaum C (2004) HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender. Psychoneuroendocrinology 29:83–98

    Article  PubMed  CAS  Google Scholar 

  181. Meador-Woodruff JH, Greden JF, Grunhaus L, Haskett RF (1990) Severity of depression and hypothalamic-pituitary-adrenal axis dysregulation: identification of contributing factors. Acta Psychiatr Scand 81:364–371

    Article  PubMed  CAS  Google Scholar 

  182. Otte C, Lenoci M, Metzler T, Yehuda R, Marmar CR, Neylan TC (2005) Hypothalamic-pituitary-adrenal axis activity and sleep in posttraumatic stress disorder. Neuropsychopharmacology 30:1173–1180

    Article  PubMed  CAS  Google Scholar 

  183. Seeman TE, Robbins RJ (1994) Aging and hypothalamic-pituitary-adrenal response to challenge in humans. Endocr Rev 15:233–260

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Pharmacology, Organon Laboratories Ltd, Newhouse, Lanarkshire, ML1 5SH, UK

    Fiona Thomson & Mark Craighead

Authors
  1. Fiona Thomson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Craighead
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fiona Thomson.

Additional information

Special issue article in honor of George Fink.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thomson, F., Craighead, M. Innovative Approaches for the Treatment of Depression: Targeting the HPA Axis. Neurochem Res 33, 691–707 (2008). https://doi.org/10.1007/s11064-007-9518-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-007-9518-3

Keywords

Search

Navigation