Post-traumatic stress disorder (PTSD) is rapidly becoming the most prevalent mental health problem facing Veterans of Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF)/Operation New Dawn (OND). PTSD is a devastating disorder that also increases risk for suicide, depression, and substance use disorders. Unfortunately, PTSD is often resistant to current therapeutic interventions and a full recovery is uncommon. The development of targeted therapies is a promising avenue for the effective treatment of PTSD, but to develop these treatments, first we must better understand the underlying neurobiological mechanisms. The goal of the proposed project is to determine whether combat Veterans with PTSD have alterations in an anxiety neural circuit mediated by the bed nucleus of the stria terminalis (BNST). In rodents, the BNST mediates anxiety, hypervigilance, and behavioral effects of stress-similar to symptoms of PTSD. In combat Veterans with PTSD, these symptoms are increased in situations where a threat is unpredictable; that is, a threatening event may or may not occur. We propose to compare OEF/OIF/OND combat-exposed Veterans with and without PTSD. We have developed novel methods to examine BNST activation to unpredictable threats using functional magnetic resonance imaging (fMRI). The study will focus on three specific aims: (1) determine whether combat Veterans with PTSD have heightened BNST activation compared to combat Veterans without PTSD; (2) identify alterations in BNST connectivity with other regions of the anxiety circuit in Veterans with PTSD; (3) determine whether stress response (measured by cortisol and skin conductance) mediates the association between BNST function (activation and connectivity) and PTSD symptoms. Ultimately we aim to elucidate the neurobiological mechanisms underlying PTSD to identify novel brain targets for treatment.
PTSD occurs in 15-30% of Veterans of Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF)/Operation New Dawn (OND). Current treatments leave substantial room for improvement. Understanding more about the underlying neurobiological mechanisms of PTSD could be used to identify new treatment targets. The purpose of the proposed study is to use in vivo brain imaging to study function in an anxiety neural circuit. The results of this project will advance our knowledge about how functional anomalies in brain neurocircuitry contribute to debilitating PTSD. Such knowledge is critical for identifying novel brain targets and guiding the development of new interventions to prevent and treat PTSD in our country's combat Veterans.
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