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Curr Psychiatry Rep. 2017 Aug 26;19(10):74. doi: 10.1007/s11920-017-0829-z.

Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic.

Author information

1
Department of Psychiatry, Yale University School of Medicine, 300 George St., Suite #901, New Haven, CT, 06511, USA. john.krystal@yale.edu.
2
Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA. john.krystal@yale.edu.
3
Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA. john.krystal@yale.edu.
4
Psychiatry Services, Yale-New Haven Hospital, New Haven, CT, USA. john.krystal@yale.edu.
5
Department of Psychiatry, Yale University School of Medicine, 300 George St., Suite #901, New Haven, CT, 06511, USA.
6
Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA.
7
Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
8
Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA.

Abstract

PURPOSE OF REVIEW:

Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity.

RECENT FINDINGS:

Here, we will briefly review evidence that PTSD might be a "synaptic disconnection syndrome" and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity. Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics.

KEYWORDS:

Connectivity; Glutamate; Ketamine; NMDA; PTSD; Plasticity; Synapse

PMID:
28844076
DOI:
10.1007/s11920-017-0829-z
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