The Role of the Glutamatergic System in Posttraumatic Stress Disorder

Nair, Jyotsna; Ajit, Sarbjot Singh

doi:10.1017/s1092852900016862

Cited by 53 publications

(32 citation statements)

References 32 publications

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“…The role of glutamate in memory formation, including trauma-related memories, and in the pathophysiology of PTSD has recently received increased attention. 6,7,35 Although acute stress enhances glutamate transmission in the prefrontal cortex, chronic stress disrupts it.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

et al. 2014

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IMPORTANCE Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition.OBJECTIVE To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. DESIGN, SETTING, AND PARTICIPANTS Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements.INTERVENTIONS Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). MAIN OUTCOMES AND MEASURESThe primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale-Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression-Severity and -Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale.RESULTS Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms. CONCLUSIONS AND RELEVANCEThis study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00749203

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Section: Discussionmentioning

confidence: 99%

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

et al. 2014

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“…The effect of glutamate is mediated by increasing the release of corticotropin-releasing factor (CRF) and subsequently activating the stress-response hormone cascade, which increases extracellular levels of glutamate and NMDA receptor expression (Nair and Singh Ajit, 2008). Increased levels of CRF have been found in the CSF of patients with PTSD (Bremner et al, 1997).…”

Section: 3mentioning

confidence: 99%

“…cause hippocampal atrophy in patients with PTSD (Nair and Singh Ajit, 2008). This is logical because glutamate at high doses is known to be neurotoxic.…”

Section: 3mentioning

confidence: 99%

“…Stress activates glutamate-NMDA receptors and decreases BDNF, and excessive amounts of glutamate can cause death of cholinergic neurons. This may account for the cognitive dysfunction associated with PTSD (Harvey et al, 2004;Nair and Singh Ajit, 2008). The antagonists of NMDA receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors (AMPA receptors) are useful in reducing anxiety-related disorders (Riaza Bermudo-Soriano et al, 2012;Walker and Davis, 2002).…”

Section: 3mentioning

confidence: 99%

“…Therefore, blocking the release of glutamate or its action would be useful in tempering the risk and progression of PTSD symptoms. Indeed, anti-glutamatergic agents such as lamotrigine improve some of the symptoms of PTSD (hyperarousal and avoidance) (Nair and Singh Ajit, 2008). The levels of GABA in the insular cortex were lower in PTSD patients than in control subjects and were associated with higher state of anxiety (Rosso et al, 2013).…”

Section: 3mentioning

confidence: 99%

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Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

Prasad¹,

Bondy

2015

Brain Research

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AnxietyPsychological damage a b s t r a c t Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

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Harvey

Vermetten

2011

Post‐Traumatic Stress Disorder

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The Role of the Glutamatergic System in Posttraumatic Stress Disorder

Cited by 53 publications

References 32 publications

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI

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