Novel Potential Molecular Target for Treatment of PTSD Identified by NARSAD Independent Investigator Grantee

Novel Potential Molecular Target for Treatment of PTSD Identified by NARSAD Independent Investigator Grantee

Posted: November 9, 2011

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A team led by NARSAD Independent Investigator Grantee Alexander Neumeister, M.D., has provided evidence of dysfunction in a key brain system linked with the occurrence of PTSD. This new discovery holds promise as a target area for the development of medication specific to post-traumatic stress disorder (PTSD). “Currently,” states Dr. Neumeister, “the only medical treatment options for the nearly eight million American adults with PTSD are antidepressants and anti-anxiety medications, which show little benefit in improving the mental health of these patients.”

The potential ‘target’, or mechanism in the brain linked with the manifestation of PTSD, is the first to be pinpointed for this brain and behavior disorder. It is the serotonin 1B receptor, whose normal function is as a receptor for the neurotransmitter serotonin, one of the chemical messengers that drives the brain’s activities. The serotonin system is known to be involved in stress response, and dysfunction in the system has been associated with PTSD. While recent work with animal models has suggested that disturbances in serotonin 1B receptor function may contribute to chronic anxiety, its specific role had not been studied previously in patients with PTSD.

To conduct the first human studies of the role of the serotonin IB receptor, Dr. Neumeister, an associate professor of psychiatry at the Mount Sinai School of Medicine, and colleagues collaborated with scientists at the Yale Positron Emission Tomography (PET) Center and the VA National Center for PTSD. Among the collaborators, Brain & Behavior Research Foundation Scientific Council Member John H. Krystal, M.D., a three-time NARSAD Grantee, is Chair of the department of psychiatry at Yale University School of Medicine and director of the Clinical Neuroscience Division of the VA National Center for PTSD.

The trials were conducted using PET scans to study the function of type 1B receptors in 96 participants: 49 with PTSD; 20 who had been exposed to trauma but did not have PTSD; and 27 non-traumatized, healthy controls. Among those who had experienced trauma were victims of childhood abuse or domestic violence and military veterans. The scans revealed that serotonin 1B levels were substantially lower in the subjects with PTSD than in those who did not have PTSD, and slightly lower in those who had been exposed to trauma but did not have PTSD.

To evaluate predictors that might explain the reduction in serotonin 1B levels in PTSD, the team examined participants’ age, age at first traumatic experience, number of traumatic experiences, sex, body mass index and whether or not they had co-existing depression, which frequently is the case with PTSD. The researchers found that age at the time of the first trauma was the factor that determined the reduction in 1B receptors and the severity of PTSD and major depression co-morbidity.

Reporting the new finding in the September issue of the journal Archives of General Psychiatry, the authors, pointing to their data as indicating “an enduring effect of trauma history” on brain function, state that “the association of early age at first trauma and more pronounced neurobiological and behavioral alterations in PTSD suggests a developmental component in the cause of PTSD.”

Says Dr. Neumeister: “Our research opens new doors in understanding PTSD and developing treatments for it, and may provide hope for these severely ill patients.”