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

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

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Excitatory Amino Acid Antagonists / pharmacology
  • Humans
  • Ketamine / pharmacology*
  • Neurobiology / methods
  • Stress Disorders, Post-Traumatic* / drug therapy
  • Stress Disorders, Post-Traumatic* / metabolism
  • Stress Disorders, Post-Traumatic* / physiopathology
  • Synaptic Transmission* / drug effects
  • Synaptic Transmission* / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • Ketamine