title: Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation.
abstract: Dissociative cognitive and perceptual alterations commonly occur at the time of traumatization and as an enduring feature of post-traumatic stress disorder (PTSD). After stress exposure, dissociative symptoms are a predictor of the development of PTSD. Recent preclinical data suggest that stress stimulates the cortico-limbic release of glutamate. The glutamate that is released during stress in animal models influences behavior, induces a variety of changes in neural plasticity that may have long-lasting effects on brain function and behavior, and contributes to neural toxicity. Antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor also stimulates transient cortico-limbic glutamate release in animals. Further, some of the effects of NMDA antagonists in animals are blocked by drugs that attenuate glutamate release. Clinical studies suggest that NMDA antagonists may transiently stimulate glutamate release and produce symptoms resembling dissociative states in humans. A recent study suggests that a drug that reduces glutamate release also attenuates the perceptual effects of the NMDA antagonist, ketamine, in humans. Because of the possible contributions of hyperglutamatergic states to the acute and long-lasting consequences of traumatic stress exposure, the therapeutic and neuroprotective potential of drugs that attenuate glutamate release should be explored in traumatized individuals with dissociative symptoms.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Chambers
authors.forename: J D
authors.initials: JD
authors.lastname: Bremner
authors.forename: B
authors.initials: B
authors.lastname: Moghaddam
authors.forename: S M
authors.initials: SM
authors.lastname: Southwick
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: J H
authors.initials: JH
authors.lastname: Krystal
mesh_terms: D000818:Animals; D004213:Dissociative Disorders / Q000503:physiopathology* / Q000523:psychology*; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology* / Q000523:psychology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018698:Glutamic Acid