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Memory and the Hippocampus in Twins

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00638885
First received: March 12, 2008
Last updated: November 3, 2014
Last verified: October 2014
  Purpose

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.


Condition
PTSD
Stress Disorders, Post-Traumatic

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Memory and the Hippocampus in Vietnam Twins With PTSD

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • hippocampal volume [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood for genetic testing, blood samples and urine and saliva collections


Estimated Enrollment: 84
Study Start Date: April 2010
Study Completion Date: June 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)

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.

  Eligibility

Ages Eligible for Study:   50 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Twins with history of military service during Vietnam era with and without PTSD

Criteria

Inclusion Criteria:

  • All twins will be required to give written informed consent.
  • Subjects will be included with a history of Vietnam Era service.
  • All subjects must be free of major medical illness on the basis of history and physical examination, lab testing, and electrocardiogram.

Exclusion Criteria:

  • Subjects will be excluded with a history of shrapnel or other foreign bodies that would preclude MRI scanning, history of loss of consciousness, or neuroleptics, sedative or benzodiazepine medication usage within the previous four weeks.
  • Subjects will also be excluded if based on the SCID interview they have comorbid:

    • schizophrenia;
    • schizoaffective disorder;
    • bulimia or anorexia, or
    • bipolar disorder.
  • Subjects will also be excluded with a history of blast injury with associated traumatic brain injury.
  • In addition, subjects will be excluded with a history of alcohol or substance abuse/dependence within the past year. We will use the strategy used in prior MRI studies and use multivariate analyses to examine the contribution of past histories of alcohol and substance abuse (as measured with the Addiction Severity Index) and depression symptom level (as measured with the Hamilton Depression Scale) to the outcomes of interest.
  • Subjects will be excluded from the study if they present with a history of serious medical or neurological illness, or as a result of routine laboratory studies, history of asthma, steroid usage, seizure disorder, or prenatal/perinatal substance exposure or trauma.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638885

Locations
United States, Georgia
Atlanta VA Medical and Rehab Center, Decatur
Decatur, Georgia, United States, 30033
Sponsors and Collaborators
Investigators
Principal Investigator: Doug Bremner, MD Atlanta VA Medical and Rehab Center, Decatur
  More Information

Additional Information:
No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00638885     History of Changes
Other Study ID Numbers: MHBA-008-07S
Study First Received: March 12, 2008
Last Updated: November 3, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
PTSD
hippocampus
twins

Additional relevant MeSH terms:
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders

ClinicalTrials.gov processed this record on November 27, 2014