Memory and the Hippocampus in Twins
Condition: PTSD; Stress Disorders, Post-Traumatic
MeSH terms: Stress Disorders, Post-Traumatic
Study type: Observational

Summary: 
      The purpose of this project is to measure brain markers and cognitive factors in twins with a
      history of military service with and without PTSD, and to follow them over time and measure
      changes in brain function and cognitive variables.
    

Detailed description: 
      Posttraumatic stress disorder (PTSD) is a condition of critical importance to the Veterans
      Health Administration that affects up to 15% of Vietnam combat veterans.1 Studies in animals
      demonstrated that stress is associated with alterations in the morphology of the hippocampus,
      a brain structure involved in learning and memory, as well as memory deficits. Patients with
      PTSD have smaller hippocampal volume on magnetic resonance imaging (MRI) and deficits in
      memory on neuropsychological testing. Animal models also show a progressive diminution of
      hippocampal volume with normal aging that is associated with a loss of memory function. In
      humans, in very old age in some individuals the hippocampus becomes smaller, with associated
      declines in memory function. Clinically, PTSD patients appear to have a more rapid rate of
      memory decline with age, which has led to their being characterized as having an "accelerated
      aging"; however there is little empiric data related to the interaction between normal aging
      and PTSD and its effect on memory. In the prior period of VA Merit funding the PI has studied
      memory and the hippocampus in twin pairs discordant for PTSD as well as normal twin pairs. We
      have studied 42 MZ and DZ twin pairs discordant for Vietnam theater exposure and discordant
      for PTSD and 28 MZ and DZ twin pairs concordant for Vietnam theater exposure and discordant
      for PTSD. All twins underwent measures of hippocampal volume, neuropsychological testing, and
      cortisol. A subset of 10 pairs of MZ pairs discordant for PTSD and combat exposure underwent
      positron emission tomography (PET) imaging of neural correlates of declarative memory
      function. Preliminary analyses are consistent with smaller hippocampal volume and deficits in
      verbal declarative memory in PTSD affected twins compared to their non-PTSD brothers who were
      not exposed to Vietnam combat.

      We now propose to measure hippocampal volume, memory function, and neural correlates of
      declarative memory, in MZ and DZ twins previously studied, who are discordant for combat and
      PTSD. We will study 42 twin pairs who were studied during 1999-2003, of whom 34 were
      discordant for PTSD at the Atlanta based assessment and had all study data including MRI,
      neuropsychological testing, and cortisol (with PET in a subsample of 10 pairs), with repeat
      measurements performed 8 years after the initial assessment, a time of life when they become
      vulnerable to memory decline associated with aging (subjects not discordant for PTSD at the
      Atlanta based assessment will also be studied as a comparison). These assessments will allow
      a comprehensive assessment of the relative impact of shared environment (e.g. family life),
      unique environment (Vietnam theater service), and genetics on the outcomes of interest. We
      hypothesize that there will be an interaction between PTSD diagnosis and aging, i.e. PTSD
      patients relative to non-PTSD will show smaller hippocampal volume as measured with MRI,
      deficits in verbal declarative memory as measured with neuropsychological testing, lower
      cortisol, and a failure of hippocampal function during memory tasks as measured with PET, and
      that the rate of decline will be greater in PTSD v non PTSD. We further hypothesize that
      analysis of all twin pair combinations will show a combined impact of genetics and PTSD
      diagnosis on the hippocampal outcomes of interest.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Twins with history of military service during Vietnam era with and without PTSD
      
Biospecimen description: 
      blood for genetic testing, blood samples and urine and saliva collections
    
Keywords: PTSD; hippocampus; twins