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Mar 17, 2011
 |  BC Innovations  |  Targets & Mechanisms

The hormone trigger in PTSD

Post-traumatic stress disorder is thought to involve changes in the circuitry of brain regions related to fear, although the specific molecular players have been elusive. Now, U.S. researchers have evidence that dysregulation of a brain hormone called PACAP and its receptor, PAC1, contributes to the disorder in women.1

Post-traumatic stress disorder (PTSD) is a syndrome of anxiety and emotional disturbance following traumatic experiences such as combat and is often confused with depression. PTSD typically is treated with talk therapy and anxiolytics.

Adenylate cyclase activating polypeptide pituitary (ADCYAP1; PACAP) and its receptor, adenylate cyclase activating polypeptide 1 pituitary receptor type I (ADCYAP1R1; PAC1), relay signals in the hypothalamus and the amygdala, the brain region in which emotions originate.

The new findings, from a team led by researchers at Emory University and The University of Vermont, draw on mouse studies and human genetic and biochemical

data to suggest that excessive PACAP-PAC1 activity leads to PTSD. The results open the door to identifying biomarkers and therapeutics to selectively diagnose and treat PTSD.

"From the standpoint of understanding the molecular mechanism of PTSD, this work is revolutionary," said Anatoly Kreinin, director of the psychiatric department at Tirat Carmel Mental Health Center. "This is one of those rare psychiatric disorders where we now know the trigger."

Blue gene

The group's biochemical and genetic studies of a cohort of highly traumatized women converged on the PACAP-PAC1 pathway.

"We were looking for genes associated with PTSD in a small genomewide

association study," said team leader Kerry Ressler, associate professor of psychiatry and behavioral sciences at Emory. "At the same time, we were...

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