Skip to main content Accessibility help
×
Home
Hostname: page-component-768ffcd9cc-jp8mt Total loading time: 0.451 Render date: 2022-12-07T07:26:11.873Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

The Role of the Glutamatergic System in Posttraumatic Stress Disorder

Published online by Cambridge University Press:  07 November 2014

Abstract

Antiglutamatergic agents, such as lamotrigine, have been used successfully for the treatment of posttraumatic stress disorder (PTSD). They could be potentially acting through the stabilization of the corticotropin-releasing factor (CRF) systems. Glutamate mediates CRF release in various brain regions involved in the pathophysiology of PTSD, antiglutamatergic agents could stabilize the CRF system and, thereby, improve the symptom complex of PTSD (reexperiencing, hyperarousal, and avoidance). The role of glutamate and CRF in PTSD and other anxiety disorders are still being elucidated. However, it is clear that the glutamatergic systems play a role in the pathophysiology of PTSD.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.Google Scholar
2.Mason, JW, Giller, EL, Kosten, TR, Ostroff, RB, Podd, L. Urinary-free cortisol levels in post-traumatic stress disorder patients. J Nerv Ment Dis. 1986;174:145159.CrossRefGoogle Scholar
3.Yehuda, R, Southwick, SM, Nussbaum, G, Wahby, V, Giller, EL Jr, Mason, JW. Low urinary cortisol excretion in PTSD J Nerv Ment Dis. 1990;178:366369.CrossRefGoogle Scholar
4.Boscarino, JA. Posttraumatic stress disorder, exposure to combat, and lower plasma cortisol among Vietnam veterans: findings and clinical implications. J Consult Clin Psychol. 1996;64:191201.CrossRefGoogle ScholarPubMed
5.Yehuda, R, Sensitization of the hypothalamic-pituitary-adrenal axis in posttraumatic stress disorder. In: McFarlane, AC, Yehuda, R, eds. Psychobiology of Posttraumatic Stress Disorder (Annals of the New York Academy of Sciences), vol. 821. New York, NY: New York Academy of Sciences; 1997:5775.Google Scholar
6.Orr, SP, Metzger, LJ, Lasko, NB, Macklin, ML, Peri, T, Pitman, RK. De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. J Abnorm Psychol. 2000;109:290298.CrossRefGoogle ScholarPubMed
7.Wessa, M, Flor, H. Failure of extinction of fear responses in posttraumatic stress disorder: evidence from second-order conditioning. Am J Psychiatry. 2007;164:16841692.CrossRefGoogle ScholarPubMed
8.Milad, MR, Orr, SP, Lasko, NB, Chang, Y, Rauch, SL, Pitman, RK. Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. J Psychiatr Res. 2008;42:515520.CrossRefGoogle ScholarPubMed
9.Sapolsky, RM. Stress and plasticity in the limbic system. Neurochem Res. 2003;28:17351742.CrossRefGoogle ScholarPubMed
10.Miller, LA, Taber, KH, Gabbard, GO, Hurley, RA. Neural underpinnings of fear and its modulation: implications for anxiety disorders. J Neuropsychiatry Clin Neurosci. 2005;17:16.CrossRefGoogle ScholarPubMed
11.Davis, M, Whalen, PJ. The amygdala: vigilance and emotion. Mol Psychiatry. 2001;6:1334.CrossRefGoogle ScholarPubMed
12.Hertzberg, MA, Butterfield, MI, Fledman, ME, et al.A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biol Psychiatry. 1999;45:12261229.CrossRefGoogle ScholarPubMed
13.Frye, MA, Ketter, TA, Kimbrell, TA, et al.A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol. 2000;607614.Google Scholar
14.Bailey, TW, Dimicco, JA. Chemical stimulation of the dorsomedial hypothalamus elevates plasma ACTH in conscious rats. Am J Physiol Regul Integr Comp Physiol. 2001;280:R8R15.CrossRefGoogle ScholarPubMed
15.Bartanusz, V, Muller, D, Gaillard, RC, Streit, P. Vutskits, L, Kiss, JZ. Local gamma-aminobutyric acid and glutamate circuit control of hypophyseotrophic corticotropin-releasing factor neuron activity in the paraventricular nucleus of the hypothalamus. Eur J Neurosci. 2004;19:777782.CrossRefGoogle ScholarPubMed
16.Davidson, JR, Stein, DJ, Shalev, AY, Yehuda, R. Posttraumatic stress disorder: acquisition, recognition, course, and treatment. J Neuropsychiatry Clin Neurosci. 2004;16(2):135141.CrossRefGoogle ScholarPubMed
17.Hageman, I, Andersen, HS, Jørgensen, MB. Post-traumatic stress disorder: a review of psychobiology and pharmacotherapy. Acta Psychiatr Scand. 2001;104:411422.CrossRefGoogle ScholarPubMed
18.Pitman, RK, Delahanty, DL. Conceptually driven pharmacologic approaches to acute trauma. CNS Spectr. 2005;10:99106.CrossRefGoogle ScholarPubMed
19.Ziegler, DR. Cullinan, WE, Herman, JP. Organization and regulation of paraventricular nucleus glutamate signaling systems: N-methyl-D-aspartate receptors. J Comp Neurol. 2005;484:4356.CrossRefGoogle ScholarPubMed
20.Herman, JP, Eyigor, O, Ziegler, DR, Jennes, L. Expression of ionotropic glutamate receptor subunit mRNAs in the hypothalamic paraventricular nucleus of the rat. J Comp Neurol. 2000;422:352362.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
21.Brann, DW, Mahesh, VB. Excitatory amino acids: evidence for a role in the control of reproduction and anterior pituitary hormone secretion. Endocr Rev. 1997;18:678700.Google ScholarPubMed
22.Kita, I, Seki, Y, Nakatani, Y, et al.Corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus are involved in arousal/yawning response of rats. Behav Brain Res. 2006;169:4856.CrossRefGoogle ScholarPubMed
23.Mathew, SJ, Coplan, JD, Schoepp, DD, Smith, EL, Rosenblum, LA, Gorman, JM. Glutamate-hypothalamic-pituitary-adrenal axis interactions: implications for mood and anxiety disorders. CNS Spectr. 2001;6:555–556, 561564.CrossRefGoogle ScholarPubMed
24.Joanny, P, Steinberg, J, Oliver, C, Grino, M. Glutamate and N-methyl-D-aspartate stimulate rat hypothalamic corticotropin-releasing factor secretion in vitro. J Neuroendocrinol. 1997;9:9397.CrossRefGoogle ScholarPubMed
25.Fudge, JL, Emiliano, AB. The extended amygdala and the dopamine system: another piece of the dopamine puzzle. J Neuropsychiatry Clin Neurosci. 2003;15:306316.CrossRefGoogle ScholarPubMed
26.Rainnie, DG, Bergeron, R, Sajdyk, TJ, Patil, M, Gehlert, DR, Shekhar, A. Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders. J Neurosci. 2004;24:34713479.CrossRefGoogle ScholarPubMed
27.Venihaki, M, Sakihara, S, Subramanian, S, et al.Urocortin III, a brain neuropeptide of the corticotropin-releasing hormone family: modulation by stress and attenuation of some anxiety-like behaviours. J Neuroendocrinol. 2004;16:411422.CrossRefGoogle ScholarPubMed
28.Gehlert, DR, Shekhar, A, Morin, SM, et al.Stress and central Urocortin increase anxiety-like behavior in the social interaction test via the CRF1 receptor. Eur J Pharmacol. 2005;509:145153.CrossRefGoogle ScholarPubMed
29.Valentino, RJ, Van Bockstaele, E. Opposing regulation of the locus coeruleus by corticotropin-releasing factor and opioids. Potential for reciprocal interactions between stress and opioid sensitivity. Psychopharmacology (Berl). 2001;158:331342.Google ScholarPubMed
30.Curtis, AL, Lechner, SM, Pavcovich, LA, Valentino, RJ. 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. 1997;281:163172.Google ScholarPubMed
31.Charney, DS, Nagy, LM, Bremner, JD, Goddard, AW, Yehuda, R, Southwick, SM. Neurobiological mechanisms of human anxiety. In: Fogel, BS, Schiffler, RB, Rao, SM, eds. Neuropsychiatry. Baltimore, Md: Williams & Wilkins; 1996:257278.Google Scholar
32.Baker, DG, Ekhator, NN, Kasckow, JW, et al.Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic stress disorder. Am J Psychiatry. 2005;162:992994.CrossRefGoogle ScholarPubMed
33.Baker, DG, West, SA, Nicholson, WE, et al.Serial CSF corticotropin-releasing hormone levels and adrenocortical activity in combat veterans with posttraumatic stress disorder. Am J Psychiatry. 1999;156:585588.Google ScholarPubMed
34.Arborelius, L, Owens, MJ, Plotsky, PM, Nemeroff, CB. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999;160:112.CrossRefGoogle ScholarPubMed
35.Mason, JW, Wang, S, Yehuda, R, et al.Marked lability in urinary cortisol levels in subgroups of combat veterans with posttraumatic stress disorder during an intensive exposure treatment program. Psychosom Med. 2002;64:238246.CrossRefGoogle ScholarPubMed
36.Mirza, NR, Bright, JL, Stanhope, KJ, Wyatt, A, Harrington, NR. Lamotrigine has an anxiolytic-like profile in the rat conditioned emotional response test of anxiety: a potential role for sodium channels? Psychopharmacology (Berl). 2005;180:159168.CrossRefGoogle ScholarPubMed
37.Höschl, C, Hajek, T. Hippocampal damage mediated by corticosteroids-a neuropsychiatric research challenge. Eur Arch Psychiatry Clin Neurosci. 2001;251(suppl 2):11811188.CrossRefGoogle Scholar
38.Kiraly, SJ, Ancill, RJ, Dimitroua, G. The relationship of endogenous cortisol to psychiatric disorder: a review. Can J Psychiatry. 1997;42:415420.CrossRefGoogle ScholarPubMed
44
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

The Role of the Glutamatergic System in Posttraumatic Stress Disorder
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

The Role of the Glutamatergic System in Posttraumatic Stress Disorder
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

The Role of the Glutamatergic System in Posttraumatic Stress Disorder
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *