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Arnsten AF, Raskind MA, Taylor FB, et al. The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder. Neurobiol Stress. 2015;1:89-99doi: 10.1016/j.ynstr.2014.10.002.
Arnsten, A. F., Raskind, M. A., Taylor, F. B., & Connor, D. F. (2015). The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder. Neurobiology of stress, 189-99. https://doi.org/10.1016/j.ynstr.2014.10.002
Arnsten, Amy F T, et al. "The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder." Neurobiology of stress vol. 1 (2015): 89-99. doi: https://doi.org/10.1016/j.ynstr.2014.10.002
Arnsten AF, Raskind MA, Taylor FB, Connor DF. The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder. Neurobiol Stress. 2015 Jan 01;1:89-99. doi: 10.1016/j.ynstr.2014.10.002. PMID: 25436222; PMCID: PMC4244027.
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Neurobiol Stress. 2015 Jan 01;1:89-99. doi: 10.1016/j.ynstr.2014.10.002.

The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder.

Neurobiology of stress

Amy F T Arnsten, Murray A Raskind, Fletcher B Taylor, Daniel F Connor

Affiliations

  1. Dept. Neurobiology, Yale University School of Medicine, New Haven, CT 06510.
  2. Madigan Army Medical Center and VA Northwest Network Mental Illness, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108.
  3. Rainier Associates, Tacoma, WA 98467.
  4. Dept. Psychiatry, University of Connecticut Medical School, Farmington, CT 06030.

PMID: 25436222 PMCID: PMC4244027 DOI: 10.1016/j.ynstr.2014.10.002

Abstract

Research on the neurobiology of the stress response in animals has led to successful new treatments for Post-Traumatic Stress Disorder (PTSD) in humans. Basic research has found that high levels of catecholamine release during stress rapidly impair the top-down cognitive functions of the prefrontal cortex (PFC), while strengthening the emotional and habitual responses of the amygdala and basal ganglia. Chronic stress exposure leads to dendritic atrophy in PFC, dendritic extension in the amygdala, and strengthening of the noradrenergic (NE) system. High levels of NE release during stress engage low affinity alpha-1 adrenoceptors, (and likely beta-1 adrenoceptors), which rapidly reduce the firing of PFC neurons, but strengthen amygdala function. In contrast, moderate levels of NE release during nonstress conditions engage higher affinity alpha-2A receptors, which strengthen PFC, weaken amygdala, and regulate NE cell firing. Thus, either alpha-1 receptor blockade or alpha-2A receptor stimulation can protect PFC function during stress. Patients with PTSD have signs of PFC dysfunction. Clinical studies have found that blocking alpha-1 receptors with prazosin, or stimulating alpha-2A receptors with guanfacine or clonidine can be useful in reducing the symptoms of PTSD. Placebo-controlled trials have shown that prazosin is helpful in veterans, active duty soldiers and civilians with PTSD, including improvement of PFC symptoms such as impaired concentration and impulse control. Open label studies suggest that guanfacine may be especially helpful in treating children and adolescents who have experienced trauma. Thus, understanding the neurobiology of the stress response has begun to help patients with stress disorders.

Keywords: clonidine; dopamine; guanfacine; norepinephrine; pediatric; prazosin

References

  1. Nat Neurosci. 2007 Mar;10(3):376-84 - PubMed
  2. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):472-7 - PubMed
  3. Dev Neuropsychol. 2000;18(3):355-81 - PubMed
  4. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6032-6 - PubMed
  5. Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17957-62 - PubMed
  6. Neuron. 1995 Mar;14(3):477-85 - PubMed
  7. Biol Psychiatry. 1999 Nov 1;46(9):1266-74 - PubMed
  8. Neuropsychiatr Dis Treat. 2012;8:131-9 - PubMed
  9. Neuropsychopharmacology. 2003 Jan;28(1):63-72 - PubMed
  10. Neuroscience. 2002;115(4):1261-79 - PubMed
  11. Int J Biol Sci. 2008 Aug 05;4(4):223-35 - PubMed
  12. Neurobiol Dis. 2013 Feb;50:96-106 - PubMed
  13. J Trauma Stress. 2010 Oct;23(5):645-8 - PubMed
  14. Psychoneuroendocrinology. 2014 May;43:105-13 - PubMed
  15. Cereb Cortex. 2009 Oct;19(10):2479-84 - PubMed
  16. Dialogues Clin Neurosci. 2011;13(3):251-62 - PubMed
  17. Front Integr Neurosci. 2012 May 11;6:16 - PubMed
  18. Proc Natl Acad Sci U S A. 2012 May 29;109(22):8746-51 - PubMed
  19. J Child Adolesc Psychopharmacol. 2012 Oct;22(5):399-402 - PubMed
  20. Behav Neurosci. 2011 Dec;125(6):797-824 - PubMed
  21. J Abnorm Psychol. 1990 Nov;99(4):398-402 - PubMed
  22. Physiol Rev. 1983 Jul;63(3):844-914 - PubMed
  23. Prog Brain Res. 1990;85:147-65; discussion 165-6 - PubMed
  24. Annu Rev Neurosci. 2009;32:289-313 - PubMed
  25. Synapse. 2013 Jun;67(6):300-12 - PubMed
  26. Neurobiol Learn Mem. 2008 Nov;90(4):616-23 - PubMed
  27. Cogn Affect Behav Neurosci. 2002 Jun;2(2):109-20 - PubMed
  28. J Psychopharmacol. 2012 Jul;26(7):958-72 - PubMed
  29. Am J Psychiatry. 2013 Sep;170(9):1003-10 - PubMed
  30. Arch Gen Psychiatry. 1993 Apr;50(4):266-74 - PubMed
  31. Brain Cogn. 2001 Feb;45(1):64-78 - PubMed
  32. Child Maltreat. 2011 Aug;16(3):216-26 - PubMed
  33. J Neurosci. 2011 May 25;31(21):7831-9 - PubMed
  34. Child Adolesc Psychiatr Clin N Am. 2014 Apr;23(2):243-56, viii - PubMed
  35. J Neurosci. 2006 Dec 20;26(51):13264-72 - PubMed
  36. J Am Acad Child Adolesc Psychiatry. 1996 Sep;35(9):1247-9 - PubMed
  37. Child Maltreat. 2000 Aug;5(3):205-17 - PubMed
  38. Psychopharmacology (Berl). 1994 Oct;116(2):143-51 - PubMed
  39. Biol Psychiatry. 2006 Oct 1;60(7):722-9 - PubMed
  40. Neural Plast. 2000;7(1-2):133-46 - PubMed
  41. Adv Pharmacol. 1998;42:781-4 - PubMed
  42. Annu Rev Neurosci. 1992;15:353-75 - PubMed
  43. Health Psychol. 2012 Mar;31(2):242-9 - PubMed
  44. Neuron. 2013 Feb 20;77(4):736-49 - PubMed
  45. Behav Brain Res. 2014 Jun 1;266:104-7 - PubMed
  46. Biol Psychiatry. 1999 Nov 1;46(9):1131-9 - PubMed
  47. Psychol Med. 1999 Jul;29(4):813-21 - PubMed
  48. J Neurosci. 1999 Jun 15;19(12):5119-23 - PubMed
  49. Adv Pharmacol. 2014;69:217-65 - PubMed
  50. Behav Neurosci. 1999 Oct;113(5):891-901 - PubMed
  51. J Neurosci. 1981 Nov;1(11):1242-59 - PubMed
  52. Neuroscience. 2011 Jan 13;172:293-302 - PubMed
  53. Neuropsychopharmacology. 2008 Jan;33(1):56-72 - PubMed
  54. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):18442-7 - PubMed
  55. Ann Clin Psychiatry. 2007 Jul-Sep;19(3):161-8 - PubMed
  56. Psychopharmacol Bull. 2008;41(1):8-18 - PubMed
  57. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6816-21 - PubMed
  58. Schizophr Res. 2012 Apr;136(1-3):104-9 - PubMed
  59. Cereb Cortex. 2005 Sep;15(9):1356-70 - PubMed
  60. Neuroimage Clin. 2014 May 13;4:808-19 - PubMed
  61. Drug Alcohol Rev. 2007 Jan;26(1):25-31 - PubMed
  62. Biol Psychiatry. 2013 Jan 1;73(1):70-4 - PubMed
  63. Nat Neurosci. 2012 Sep;15(9):1184-91 - PubMed
  64. Neuron. 2012 Oct 4;76(1):223-39 - PubMed
  65. Arch Gen Psychiatry. 2009 Nov;66(11):1221-32 - PubMed
  66. J Neurosci. 2006 Jul 26;26(30):7870-4 - PubMed
  67. J Affect Disord. 2014 Oct;168:387-98 - PubMed
  68. Arch Gen Psychiatry. 1998 Apr;55(4):362-8 - PubMed
  69. Trends Neurosci. 1998 Dec;21(12):505-9 - PubMed
  70. Biol Psychiatry. 2008 Mar 15;63(6):629-32 - PubMed
  71. Biol Psychiatry. 2011 Jun 15;69(12):e55-68 - PubMed
  72. Neurobiol Stress. 2015 Jan 1;1:23-32 - PubMed
  73. Biol Psychiatry. 2012 Aug 15;72(4):258-65 - PubMed
  74. Nat Rev Neurosci. 2009 Jun;10(6):410-22 - PubMed
  75. J Child Adolesc Psychopharmacol. 2009 Aug;19(4):475-6 - PubMed
  76. J Neurosci. 1996 Aug 1;16(15):4787-98 - PubMed
  77. Neuroreport. 1995 Aug 21;6(12):1605-10 - PubMed
  78. Biol Psychiatry. 2009 Jul 1;66(1):25-32 - PubMed
  79. J Psychosom Res. 2012 Feb;72(2):89-96 - PubMed
  80. Front Behav Neurosci. 2013 Apr 10;7:30 - PubMed
  81. Pharmacol Biochem Behav. 2005 Jan;80(1):63-7 - PubMed
  82. J Comp Neurol. 1979 Sep 1;187(1):117-43 - PubMed
  83. Arch Gen Psychiatry. 1997 Mar;54(3):246-54 - PubMed
  84. Curr Opin Neurobiol. 1996 Apr;6(2):237-42 - PubMed
  85. J Neuroendocrinol. 1998 Oct;10(10):743-57 - PubMed
  86. Biol Psychiatry. 2007 Apr 15;61(8):928-34 - PubMed
  87. J Child Adolesc Psychopharmacol. 2009 Oct;19(5):599-600 - PubMed
  88. Anat Rec A Discov Mol Cell Evol Biol. 2006 Jan;288(1):26-35 - PubMed
  89. Neuron. 2005 Oct 20;48(2):175-87 - PubMed
  90. J Cogn Neurosci. 2008 Mar;20(3):447-57 - PubMed
  91. Adv Pharmacol. 1998;42:740-4 - PubMed
  92. Prog Brain Res. 1991;88:293-305 - PubMed
  93. J Am Acad Child Adolesc Psychiatry. 2003 Apr;42(4):384-5 - PubMed
  94. Biol Psychiatry. 1999 Nov 1;46(9):1259-65 - PubMed
  95. Psychiatry Res. 2012 Aug-Sep;203(2-3):139-45 - PubMed
  96. J Neurosci. 2002 Aug 1;22(15):6810-8 - PubMed
  97. J Comp Neurol. 1989 Aug 15;286(3):353-75 - PubMed
  98. Biol Psychiatry. 2006 Apr 1;59(7):577-81 - PubMed
  99. Alcohol Clin Exp Res. 2012 Feb;36(2):351-60 - PubMed
  100. Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16655-60 - PubMed
  101. Alcohol Clin Exp Res. 2009 Feb;33(2):255-63 - PubMed
  102. Cortex. 2013 Jul-Aug;49(7):1884-91 - PubMed
  103. Neuropsychopharmacology. 2013 Sep;38(10):1833-43 - PubMed
  104. Arch Gen Psychiatry. 2009 Aug;66(8):888-96 - PubMed
  105. Biol Psychiatry. 2003 May 15;53(10):879-89 - PubMed
  106. Neuropsychologia. 1987;25(2):359-65 - PubMed
  107. Neuroscience. 1995 Feb;64(3):619-28 - PubMed
  108. J Neurosci. 1997 Nov 1;17(21):8528-35 - PubMed
  109. Am J Psychiatry. 2006 Dec;163(12):2186-8 - PubMed
  110. Science. 2004 Oct 29;306(5697):882-4 - PubMed
  111. J Comp Neurol. 1998 May 25;395(1):1-17 - PubMed
  112. Curr Opin Neurobiol. 1992 Dec;2(6):759-63 - PubMed
  113. J Am Acad Child Adolesc Psychiatry. 1996 Aug;35(8):975-6 - PubMed
  114. J Clin Psychol. 1976 Jul;32(3):654-8 - PubMed
  115. Neuropsychopharmacology. 2003 Sep;28(9):1589-96 - PubMed
  116. Ann Pharmacother. 2011 Dec;45(12):1590-1 - PubMed
  117. Neuron. 2010 Dec 9;68(5):815-34 - PubMed
  118. Mol Psychiatry. 2006 Feb;11(2):187-95 - PubMed
  119. Biol Psychiatry. 2010 Feb 15;67(4):304-8 - PubMed
  120. Psychopharmacol Bull. 2007;40(1):8-30 - PubMed
  121. Neurosci Lett. 2003 Jan 30;337(1):29-32 - PubMed
  122. Biol Psychiatry. 2015 Dec 15;78(12 ):860-70 - PubMed
  123. Philos Trans R Soc Lond B Biol Sci. 1996 Oct 29;351(1346):1463-70; discussion 1470-1 - PubMed
  124. Biol Psychiatry. 2005 Dec 1;58(11):894-900 - PubMed
  125. Cereb Cortex. 2000 Mar;10(3):206-19 - PubMed
  126. Biol Psychiatry. 2012 Jul 1;72(1):57-64 - PubMed
  127. Prog Mol Biol Transl Sci. 2014;122:211-31 - PubMed
  128. Exp Neurol. 2005 Nov;196(1):199-203 - PubMed
  129. Am J Psychiatry. 2001 Aug;158(8):1227-30 - PubMed
  130. J Neurosci. 2006 Feb 1;26(5):1571-8 - PubMed
  131. Ther Adv Psychopharmacol. 2014 Feb;4(1):43-7 - PubMed
  132. Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):912-7 - PubMed
  133. J Trauma Acute Care Surg. 2013 Jul;75(1):161-5 - PubMed
  134. J Neurosci. 2000 Feb 15;20(4):1568-74 - PubMed
  135. J ECT. 2014 Mar;30(1):e9-10 - PubMed
  136. Pharmacol Biochem Behav. 1997 Sep;58(1):55-9 - PubMed
  137. Brain Res. 1975 Jul 11;92(2):291-306 - PubMed
  138. Am J Psychiatry. 2003 Feb;160(2):371-3 - PubMed
  139. Behav Neural Biol. 1994 Sep;62(2):134-9 - PubMed
  140. J Child Adolesc Psychopharmacol. 2013 May;23(4):244-51 - PubMed
  141. J Neurochem. 1992 Feb;58(2):494-502 - PubMed
  142. Philos Trans R Soc Lond B Biol Sci. 1996 Oct 29;351(1346):1445-53 - PubMed
  143. Cell. 2007 Apr 20;129(2):397-410 - PubMed
  144. Neuropsychopharmacology. 2011 Jul;36(8):1593-8 - PubMed
  145. Eur J Neurosci. 2003 Apr;17 (7):1411-24 - PubMed
  146. J Geriatr Psychiatry Neurol. 2003 Sep;16(3):165-71 - PubMed
  147. Pediatrics. 2012 Jan;129(1):e232-46 - PubMed
  148. Brain Res Cogn Brain Res. 2003 Jul;17(2):212-22 - PubMed
  149. Science. 1998 Jun 12;280(5370):1711-2 - PubMed
  150. Nature. 2009 Jun 11;459(7248):837-41 - PubMed
  151. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1325-9 - PubMed
  152. Prog Brain Res. 1990;85:367-402; discussion 402-3 - PubMed

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