Norepinephrine Transporter Availability in PTSD

The objective of this proposal is to collect pilot data to characterize the binding of
[11C]MENET in combat-exposed war veterans with posttraumatic stress disorder (PTSD).
Approximately two hundred thousand veterans will be returning stateside upon the end of
combat operations in Iraq, and 13% of returning veterans will have PTSD. 15% of all war
veterans will develop chronic PTSD symptoms requiring a lifetime of mental health care.
Little is known about the dysregulation of PTSD veteran's neurochemical state including the
noradrenergic system which plays a primary role in memory and stress response. This includes
heightened anxiety, fear and hyperarousal symptoms characteristic of PTSD. The noradrenergic
system is a concentration of neurons in the brainstem nucleus, locus coerulues, that have
projections to the amygdale and prefrontal cortex. The norepinephrine transporter (NET) is
responsible for regulating and terminating noradrenergic transmission, and is a specific
marker for neuronal integrity. Hyperactivity of the noradrenergic system up-regulates NET
protein. An unresolved problem in studying the noradrenergic system is identification of
suitable radiopharmaceutical to non-invasively measure alterations in the density of NET.
The investigators propose to address this challenge by using positron emission tomography
(PET) to measure stress-induced changes in NET expression in combat-exposed war veterans
with PTSD. The central hypothesis of this proposal is that war veterans with PTSD have an
up-regulation of NET in the locus coerulues resulting from hyperactivity of the
noradrenergic system compared to healthy controls. Through a series of experiments, the
investigators will determine the in vivo binding characteristics of [11C]MENET. The
investigators will use this information to optimally design an experimental protocol to
measure the availability of NET in a pilot group of combat-exposed war veterans with PTSD.
The aims of this proposal are: 1) Measure the uptake kinetics and whole brain distribution
of [11C]MENET in combat-exposed veterans with PTSD and healthy controls, 2) Develop a
quantitative kinetic model of [11C]MENET uptake to calculate the NET availability in brain.
The subjects undergoing imaging in this work will be recruited by Dr. J. Douglas Bremner
(Co-Investigator) at Emory University and Atlanta Veteran Affairs Hospital. Our long-term
goal is to develop a longitudinal study framework to assess the NETs dysregulation during
onset of PTSD as well as its transition to chronic lifetime PTSD.