Norepinephrine Transporter Availability in PTSD
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    


Intervention name(s): [C-11]MENET
Intervention type(s): Drug
Intervention description(s): PET imaging involves injecting small amounts of a radioactive material into the blood stream. The radioactive material is attached to a drug called MENET that will give information about how the brain interacts with a protein called norepinephrine (NE).
Other intervention name(s): (2S,3S)-2-[alpha-(2-[11C]- methylphenoxy)phenylmethyl]morpholine([11C]MENET)
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: PTSD