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New Genetic Clues to Posttraumatic Stress Disorder

Findings May Help Point the Way to Tests and Treatment for PTSD
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A Biomarker for PTSD continued...

They cross-referenced genes and proteins found in those samples with genes and proteins that were amplified in the brains of mice that were exposed to fear.

“The PACAP receptor was the very top of the list when we combined both gene sets,” Ressler says.

When they tested for PACAP in the blood samples from their traumatized patients, they found that women with high levels of this protein were more likely to have PTSD than those who had lower levels, but there was no such association in men.

So in the next round of sleuthing, they looked at the specific genes that code for PACAP and its receptor, a kind of docking station that allows a signaling protein to attach to a cell and deliver its instructions.

When they tested 798 traumatized people, they found that women, but not men, diagnosed with PTSD were far more likely to carry a certain variant of the PACAP receptor gene than those who were not.

And they couldn’t figure out why it was only turning up in women.

“So we were scratching our heads about that for a while,” Ressler says.

Until they looked more closely and saw that the region of the gene where the variant was located sat squarely in the middle of something called an estrogen response element, or a piece of DNA that gets switched on by the hormone estrogen.

“We just couldn’t believe it,” Ressler says. “This is one of the stories in science that you kind of live your career for. Where every time you looked at something it continued to go in the same direction in a robust way and make more and more sense.”

What Ressler and his team had, they knew, was an exciting correlation between two things, the PACAP receptor and higher rates of PTSD in their study participants, but they didn’t have any proof that one caused the other.

So they went further, experimentally startling study participants by hitting them with a blast of air or sounding a loud noise in the dark. Those who reacted most strongly were the more likely to carry the genetic variant for the PACAP receptor than those who didn’t startle as easily.

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