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Restoring Lost Synapses May Speed Up Response in Treating Depression and PTSD

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The helpless behavior commonly linked to depression and post-traumatic stress disorder (PTSD) is preceded by stress-related loss of synapses -- the mechanism of communication between neurons -- in the brain�s hippocampal region, according to researchers at Yale University School of Medicine led by NARSAD Investigator Tibor Hajszan, M.D. and reported in the March 1 issue of Biological Psychiatry.

Researchers have suspected for years that changes in synapses may play a role in the neurobiology of depression and post-traumatic stress disorder (PTSD). Among well-known studies, those by NARSAD Scientific Council Member Bruce McEwen, Ph.D., have indicated that stress could cause neurons to shrink or retract their connections.

The research directed by Dr. Hajszan suggests that in learned helplessness, an animal model for depression and PTSD, stress-related reductions in synapses in the hippocampus are directly related to the emergence of depression-like behavior. He and his team studied helpless behavior in rats and used electron microscopy to analyze directly what happens to hippocampal synapses in the presence or absence of helpless behavior.

�Because synapses have the potential for rapid response, synapse loss probably underlies the rapid deterioration of mood that depressed patients sometimes experience,� Dr. Hajszan said. �In clinical practice, the main problem with antidepressants is that they require weeks to exert their effect.� He stated that �there are ways to restore these lost hippocampal synapses in as little as hours or even minutes, and our laboratory is currently testing rapid-acting antidepressants that could provide immediate relief from depressive symptoms.�

The Yale team used a six-day treatment with the antidepressant desipramine to reverse the rats� helpless behavior and restore their hippocampal synapses.

(This article was adapted with permission from Yale University.)


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