Display options
Cite
Tafet GE, Nemeroff CB. Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis. Front Psychiatry. 2020;11:443doi: 10.3389/fpsyt.2020.00443.
Tafet, G. E., & Nemeroff, C. B. (2020). Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis. Frontiers in psychiatry, 11443. https://doi.org/10.3389/fpsyt.2020.00443
Tafet, Gustavo E, and Nemeroff, Charles B. "Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis." Frontiers in psychiatry vol. 11 (2020): 443. doi: https://doi.org/10.3389/fpsyt.2020.00443
Tafet GE, Nemeroff CB. Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis. Front Psychiatry. 2020 May 15;11:443. doi: 10.3389/fpsyt.2020.00443. eCollection 2020. PMID: 32499732; PMCID: PMC7243209.
Copy Download .nbib Format: NLM
Share it on

Front Psychiatry. 2020 May 15;11:443. doi: 10.3389/fpsyt.2020.00443. eCollection 2020.

Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis.

Frontiers in psychiatry

Gustavo E Tafet, Charles B Nemeroff

Affiliations

  1. Department of Psychiatry and Neurosciences, Maimónides University, Buenos Aires, Argentina.
  2. Department of Psychiatry, University of Texas at Austin, Austin, TX, United States.

PMID: 32499732 PMCID: PMC7243209 DOI: 10.3389/fpsyt.2020.00443

Abstract

Stress in general, and early life stress in particular, has been associated with the development of anxiety and mood disorders. The molecular, biological and psychological links between stress exposure and the pathogenesis of anxiety and mood disorders have been extensively studied, resulting in the search of novel psychopharmacological strategies aimed at targets of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperactivity of the HPA axis has been observed in certain subgroups of patients with anxiety and mood disorders. In addition, the effects of different anti-anxiety agents on various components of the HPA axis has been investigated, including benzodiazepines, tricyclic antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs). For example, benzodiazepines, including clonazepam and alprazolam, have been demonstrated to reduce the activity of corticotrophin releasing factor (CRF) neurons in the hypothalamus. TCAs and SSRIs are also effective anti-anxiety agents and these may act, in part, by modulating the HPA axis. In this regard, the SSRI escitalopram inhibits CRF release in the central nucleus of the amygdala, while increasing glucocorticoid receptor (GRs) density in the hippocampus and hypothalamus. The molecular effects of these anti-anxiety agents in the regulation of the HPA axis, taken together with their clinical efficacy, may provide further understanding about the role of the HPA axis in the pathophysiology of mood and anxiety disorders, paving the way for the development of novel therapeutic strategies.

Copyright © 2020 Tafet and Nemeroff.

Keywords: anxiety; corticotropin releasing hormone; hypothalamic-pituitary-adrenal; pharmacology; stress

References

  1. Eur J Neurosci. 2002 Aug;16(3):381-5 - PubMed
  2. Psychoneuroendocrinology. 2011 Apr;36(3):415-25 - PubMed
  3. J Clin Psychiatry. 2004;65 Suppl 1:18-28 - PubMed
  4. Mol Brain. 2014 Jul 10;7:49 - PubMed
  5. J Clin Invest. 1991 Mar;87(3):831-7 - PubMed
  6. Biol Psychiatry. 2000 Oct 15;48(8):778-90 - PubMed
  7. Ann N Y Acad Sci. 2004 Jun;1018:35-45 - PubMed
  8. Synapse. 2004 Jul;53(1):11-9 - PubMed
  9. Neuron. 2002 Mar 28;34(1):13-25 - PubMed
  10. World J Biol Psychiatry. 2007;8(4):269-72 - PubMed
  11. Pol J Pharmacol. 2002 Jul-Aug;54(4):343-9 - PubMed
  12. Trends Pharmacol Sci. 1992 Jan;13(1):35-41 - PubMed
  13. J Neurosci. 1983 Jul;3(7):1355-68 - PubMed
  14. Psychopharmacology (Berl). 1992;108(1-2):23-6 - PubMed
  15. Front Neuroendocrinol. 2012 Jan;33(1):67-84 - PubMed
  16. Mol Psychiatry. 1999 Mar;4(2):106-8 - PubMed
  17. Trends Neurosci. 1995 Jan;18(1):6-11 - PubMed
  18. Pharmacopsychiatry. 1996 Jan;29(1):12-22 - PubMed
  19. Biol Psychiatry. 1996 Apr 15;39(8):703-7 - PubMed
  20. Prog Neurobiol. 2009 May;88(1):17-31 - PubMed
  21. J Pharmacol Exp Ther. 2001 Nov;299(2):401-7 - PubMed
  22. PLoS One. 2018 Oct 1;13(10):e0204980 - PubMed
  23. Neuroscience. 2002;113(3):581-92 - PubMed
  24. Front Cell Neurosci. 2016 Nov 24;10:272 - PubMed
  25. Pharmacopsychiatry. 1986 Jan;19(1):19-22 - PubMed
  26. Neuropsychopharmacology. 2003 Feb;28(2):206-15 - PubMed
  27. Science. 1984 Dec 14;226(4680):1342-4 - PubMed
  28. Endocrinology. 2008 Jul;149(7):3512-20 - PubMed
  29. J Cell Sci. 2012 May 15;125(Pt 10):2486-99 - PubMed
  30. Brain Res Mol Brain Res. 1989 Jul;6(1):77-83 - PubMed
  31. Brain Res. 2006 Jan 5;1067(1):164-9 - PubMed
  32. Neurosci Res. 2005 Oct;53(2):129-39 - PubMed
  33. J Neurosci. 1988 Jul;8(7):2517-29 - PubMed
  34. Synapse. 1989;4(3):196-202 - PubMed
  35. Neuropsychopharmacology. 2000 Nov;23(5):477-501 - PubMed
  36. Eur Neuropsychopharmacol. 1992 Jun;2(2):107-13 - PubMed
  37. Neuron. 1998 Apr;20(4):727-40 - PubMed
  38. Ann N Y Acad Sci. 2003 Apr;985:389-410 - PubMed
  39. Biol Psychiatry. 1999 Dec 1;46(11):1461-71 - PubMed
  40. J Neurosci. 2000 Jun 1;20(11):4030-6 - PubMed
  41. J Pharm Pharmacol. 1984 Feb;36(2):134-5 - PubMed
  42. Dialogues Clin Neurosci. 2005;7(2):103-23 - PubMed
  43. Nat Rev Neurosci. 2005 Jun;6(6):463-75 - PubMed
  44. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13456-61 - PubMed
  45. EMBO J. 1993 Jan;12(1):145-56 - PubMed
  46. Neuroscientist. 2016 Feb;22(1):26-45 - PubMed
  47. J Neurochem. 1989 Nov;53(5):1644-7 - PubMed
  48. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Sep;27(6):893-903 - PubMed
  49. Neuro Endocrinol Lett. 2009 Mar;30(1):11-6 - PubMed
  50. Psychoneuroendocrinology. 2013 Aug;38(8):1349-61 - PubMed
  51. Brain Res. 1998 Nov 30;813(1):112-20 - PubMed
  52. Stress. 2005 Dec;8(4):233-46 - PubMed
  53. J Neurosci. 1985 Dec;5(12):3189-203 - PubMed
  54. Behav Brain Res. 2006 Nov 11;174(2):215-24 - PubMed
  55. Endocrinology. 1985 Dec;117(6):2505-11 - PubMed
  56. Mol Endocrinol. 1999 Oct;13(10):1629-44 - PubMed
  57. J Abnorm Psychol. 1978 Feb;87(1):49-74 - PubMed
  58. J Comp Neurol. 1993 Jun 1;332(1):1-20 - PubMed
  59. Ann N Y Acad Sci. 2003 Apr;985:420-44 - PubMed
  60. Mol Pharmacol. 1992 Jun;41(6):1016-22 - PubMed
  61. J Pharmacol Exp Ther. 1991 Jul 1;258(1):349-56 - PubMed
  62. Stress. 1996 Jul;1(1):1-19 - PubMed
  63. Brain Res. 2008 Oct 31;1238:93-107 - PubMed
  64. Brain Res Bull. 2000 Sep 1;53(1):95-104 - PubMed
  65. J Neurosci. 1996 Apr 1;16(7):2365-72 - PubMed
  66. Cell. 2012 May 25;149(5):1152-63 - PubMed
  67. Int J Mol Sci. 2020 Jan 13;21(2): - PubMed
  68. Mol Endocrinol. 1988 Dec;2(12):1311-9 - PubMed
  69. Endocr Rev. 1996 Apr;17(2):187-205 - PubMed
  70. Brain Res. 1993 Oct 8;624(1-2):188-98 - PubMed
  71. Psychoneuroendocrinology. 2013 Feb;38(2):300-5 - PubMed
  72. J Clin Endocrinol Metab. 1997 Aug;82(8):2601-6 - PubMed
  73. Prog Brain Res. 1987;72:3-9 - PubMed
  74. Cogn Affect Behav Neurosci. 2001 Dec;1(4):388-93 - PubMed
  75. Pharmacol Ther. 2011 Feb;129(2):120-48 - PubMed
  76. Curr Opin Neurobiol. 1992 Apr;2(2):191-7 - PubMed
  77. Depress Anxiety. 2007;24(1):66-76 - PubMed
  78. Am J Geriatr Psychiatry. 2011 May;19(5):482-90 - PubMed
  79. J Neuropsychiatry Clin Neurosci. 2016 Spring;28(2):77-88 - PubMed
  80. Annu Rev Biochem. 1999;68:821-61 - PubMed
  81. Neuron. 1998 Apr;20(4):709-26 - PubMed
  82. Biochim Biophys Acta. 2007 Apr;1768(4):825-35 - PubMed
  83. Mol Psychiatry. 2016 Feb;21(2):252-60 - PubMed
  84. Prog Brain Res. 1987;72:11-26 - PubMed
  85. Dialogues Clin Neurosci. 2002 Mar;4(1):31-46 - PubMed
  86. Neuropsychopharmacology. 1992 Feb;6(2):69-75 - PubMed
  87. Endocrinology. 1988 Oct;123(4):2117-23 - PubMed
  88. Brain Res. 1994 Sep 19;657(1-2):141-9 - PubMed
  89. Trends Endocrinol Metab. 2001 Dec;12(10):453-60 - PubMed
  90. Biol Psychiatry. 2001 Jun 15;49(12):1023-39 - PubMed
  91. Ann N Y Acad Sci. 1993 Oct 29;697:173-88 - PubMed
  92. Cell Tissue Res. 1994 Aug;277(2):289-95 - PubMed
  93. Mol Cell Neurosci. 2011 Jan;46(1):55-66 - PubMed
  94. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):189-92 - PubMed
  95. Brain Behav Immun. 2016 Jan;51:154-68 - PubMed
  96. Am J Psychiatry. 2004 Aug;161(8):1397-403 - PubMed
  97. Mol Cell Neurosci. 2004 Nov;27(3):280-95 - PubMed
  98. Biol Psychiatry. 1999 Nov 1;46(9):1181-91 - PubMed
  99. Biol Psychiatry. 2001 May 1;49(9):753-62 - PubMed
  100. J Endocrinol. 1999 Jan;160(1):1-12 - PubMed
  101. JAMA. 1992 Mar 4;267(9):1244-52 - PubMed
  102. Front Behav Neurosci. 2014 Sep 12;8:318 - PubMed
  103. Mol Cell Endocrinol. 1990 Apr 17;70(2):165-74 - PubMed
  104. Am J Psychiatry. 1996 Aug;153(8):1037-42 - PubMed
  105. Cell Signal. 2010 Oct;22(10):1406-12 - PubMed
  106. Trends Neurosci. 1990 May;13(5):184-8 - PubMed
  107. Psychoneuroendocrinology. 2012 Jan;37(1):27-38 - PubMed
  108. Pharmacol Rev. 1991 Dec;43(4):425-73 - PubMed
  109. Biol Psychiatry. 2000 Oct 15;48(8):732-9 - PubMed
  110. Mol Brain. 2017 Jun 24;10(1):28 - PubMed
  111. Psychoneuroendocrinology. 2008 Jul;33(6):693-710 - PubMed
  112. J Psychiatr Res. 1993;27 Suppl 1:209-20 - PubMed
  113. N Engl J Med. 1988 Aug 11;319(6):348-53 - PubMed
  114. Cell Mol Neurobiol. 1993 Aug;13(4):349-72 - PubMed
  115. Handb Exp Pharmacol. 2014;220:461-79 - PubMed
  116. Brain Res. 1998 Mar 30;788(1-2):305-10 - PubMed
  117. Horm Behav. 2006 Nov;50(4):550-61 - PubMed
  118. J Psychopharmacol. 1998;12(2):115-21 - PubMed
  119. Cogn Affect Behav Neurosci. 2001 Mar;1(1):96-104 - PubMed
  120. Brain Struct Funct. 2008 Sep;213(1-2):63-72 - PubMed
  121. Endocr Rev. 1993 Jun;14(3):269-90 - PubMed
  122. Brain Res. 1988 Oct 25;463(1):28-36 - PubMed
  123. Psychoneuroendocrinology. 2018 Jan;87:74-82 - PubMed
  124. Biol Psychiatry. 2013 Nov 15;74(10):760-7 - PubMed
  125. Neurosci Biobehav Rev. 2006;30(2):203-14 - PubMed
  126. Brain Res. 1992 Feb 14;572(1-2):117-25 - PubMed
  127. J Psychiatry Neurosci. 2004 May;29(3):185-93 - PubMed
  128. Annu Rev Neurosci. 1999;22:105-22 - PubMed
  129. Arch Gen Psychiatry. 1997 Jul;54(7):597-606 - PubMed
  130. Neurosci Lett. 1997 Jul 11;230(1):57-60 - PubMed
  131. Annu Rev Neurosci. 2000;23:155-84 - PubMed
  132. Trends Neurosci. 1997 Feb;20(2):78-84 - PubMed
  133. J Clin Psychopharmacol. 1987 Dec;7(6 Suppl):24S-35S - PubMed
  134. Brain Res. 1985 Mar 25;330(2):253-63 - PubMed
  135. Neuroscience. 2003;118(4):975-84 - PubMed
  136. J Clin Endocrinol Metab. 1990 May;70(5):1462-71 - PubMed
  137. J Neurosci. 2002 May 1;22(9):3673-82 - PubMed
  138. Eur Neuropsychopharmacol. 2016 Mar;26(3):397-410 - PubMed
  139. Eur J Neurosci. 2010 Mar;31(5):892-902 - PubMed
  140. Biol Psychiatry. 1998 Apr 15;43(8):547-73 - PubMed

Publication Types