U. TEXAS (US)—Drugs that have shown success in clinical trials for Alzheimer’s and Huntington’s diseases may also be useful in treating post-traumatic stress disorder (PTSD).
The severe anxiety disorder is estimated to afflict as many as one in eight returning Iraq and Afghanistan veterans. Symptoms include flashbacks, an excessive startle response, depression, anxiety, and insomnia—some of which can persist over long periods of time.
The drugs, known as HDAC inhibitors, have “never been tested in PTSD. The results of this study suggest that they should be,” says Igor Ponomarev, a research assistant professor at the University of Texas at Austin.
The study appears in the journal Neuropsychopharmocology.
PTSD occurs when the brain’s system for regulating stress overloads to the point where it can no longer revert to a normal state, even after the cause of the stress disappears. Particularly affected is the amygdala, which is one of the critical structures in the brain related to learning and memory, and in particular to fear-related learning and memory.
Those suffering from PTSD can end up with an amygdala that is on high alert for mild stressors and stimuli that are evocative of the original source of the stress.
Ponomarev and coauthor R. Adron Harris, professor of neurobiology, used a rat model of PTSD to trace these broad changes in the amygdala down to the level of gene expression.
“What we found were that genes that are known to be involved in excitation and inhibition changed their expression three weeks after stress,” says Ponomarev. “The overall result is an amygdala that’s unable to normally respond to stressors.”
The researchers found that severe stress—like the kind that produces PTSD—can result in the increased expression of certain genetic elements that had, until recently, been dismissed by neuroscientists as “junk DNA.”
These particular DNA sequences may prove significant, says Ponomarev, because they seem to be involved in, or indicative of, a process known as “chromatin remodeling,” which helps determine which genes are or are not expressed in a given cell. It’s precisely this process that seems to be responsive to the HDAC inhibitors.
“It’s a hot area in neuropsychiatric disorders,” he says, “because there are some pharmacological compounds that can block or promote chromatin remodeling.
“It’s possible to imagine that some of the long-term changes in gene expression, which we’ve seen result from severe stress, could be reversed or modulated by the drugs.”
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