Neurobiology of Sleep and Sleep Treatment Response in Returning Veterans

Not Applicable

Completed

Brief Summary: The overarching objectives of this study are: 1) To investigate the neurobiology of posttraumatic stress disorder (PTSD) during Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) sleep relative to wakefulness; 2) To identify the neurobiological underpinnings of sleep treatment response to prazosin or placebo during wakefulness, REM sleep, and NREM sleep in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) ( veterans with PTSD; and 3) To explore pre-treatment brain activity patterns during wakefulness, REM sleep, and NREM sleep that predict sleep treatment response. We will also explore the stability of the Positron Emission Tomography (PET) signal by comparing pre- and post-placebo changes in brain glucose metabolism in non-responders. For non-PTSD veterans, the stability of the PET signal will be evaluated in a subsample of 6 veterans without PTSD who will repeat the PET imaging procedures 8 weeks after the initial PET series.

The overarching hypothesis is that PTSD is characterized by neurobiological alterations in the amygdala, medial prefrontal cortex (mPFC), and brain centers involved in the regulation of NREM and REM sleep, and that these neurobiological changes are normalized with effective sleep treatment.

Detailed Description: PTSD affects both daytime functioning and sleep. Complaints of poor sleep, objective disruption of sleep, and heightened sympathovagal tone during sleep occurring early after trauma exposure increase the risk of developing PTSD up to one year later. (1-4). Insomnia is one the most common reasons for referral to mental health services in active duty personnel (5). In military personnel returning from Iraq and Afghanistan, more than 70 percent of those with PTSD report sleep problems and fatigue, whereas more than 25% percent of those without PTSD endorse these symptoms (6). Other disruptive nocturnal behaviors and sleep disorders including sleep terrors, nocturnal anxiety attacks, simple and complex motor behaviors and vocalizations, acting out dreams, sleep apnea, and periodic leg movement disorders are also frequently reported by PTSD patients (7-12). In PTSD, sleep disturbances independently contribute to poor clinical outcomes such as increased severity of daytime PTSD symptoms (8), depression (13), suicidality (13), general psychiatric distress (14), poorer quality of life and functioning (14), poorer perceived physical health (14), and increased substance use (15;16).

Recruitment & Eligibility

Inclusion Criteria

Additional selection criteria for PTSD subjects are:

Trauma occurred three months or more before study entry
Meeting diagnostic criteria for current PTSD according to the Clinician Administered PTSD Scale (CAPS)
Participants will remain in ongoing counseling services

Additional selection criterion for non-PTSD healthy subjects:

Not meet DSM-IV diagnostic criteria for current PTSD
Have a total score < 13 on the Beck Depression Inventory
Participants who are active-duty military personnel will be required to obtain permission from their commander to participate in this study.

Exclusion Criteria

Current diagnosis of untreated, severe depression as determined by the Structured Clinical Interview for Diagnostic and Statistical Manual- IV Edition (DSM-IV), non-patient version
Beck Depression Inventory > 30
History of psychotic or bipolar disorder
Current history (within 3 months) of substance or alcohol abuse
Significant or unstable acute or chronic medical conditions
Other current sleep disorders
Presence of implanted devices or metal in body such as cardiac pacemaker, aneurysm clip, ear implant, shrapnel, neurostimulators or other metal devices
Fear of closed spaces
Previous radiation exposure (past year) that exceeds recommended safety limits
Pregnancy or breast feeding
Resting blood pressure < 90/60 at the screening physical examination
Heart rate > 100 beats/minutes
Current use of a beta-blocker
Use of an alpha-1 antagonist agent in the previous 3 weeks
Refusal to follow the safety measures in the case of use of a phosphodiesterase 5 inhibitor (Cialis, Viagra, Levitra)
Unexpected, untreated, or serious EKG findings

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	A placebo is a sugar pill, which will be used to compare with the results of the active medication
Prazosin	Prazosin	Active medication arm. Prazosin is an FDA approved medication, originally designed as an anti-hypertension medication. Side effects of the medication in some include sleepiness and once asleep, sustained sleep.

Primary Outcome Measures

Name	Time	Method
Whole Brain Relative Regional Cerebral Metabolic Rate of Glucose	Baseline and post-intervention at 8-10 weeks	The reported Z value reflect the magnitude of the state difference (Wake vs. Non-REM or Wake vs. REM) within the prazosin group pre-to-post treatment, and after using a mask to adjust for the spurious effects of the passage of time.

Secondary Outcome Measures

Name	Time	Method
Pittsburgh Sleep Quality Index (PSQI):	Baseline and post-treatment at 8-10 weeks	Self-report sleep quality measure. Scores range from 0 to 21, with higher scores reflecting poorer sleep quality.