Memory and the Hippocampus in Twins
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Group 1
|
Outcome Measures
Primary Outcome Measures
- Neuropsychological Testing of Memory [2 days]
Percent retention on the Wechsler Memory Scale - Logical
Eligibility Criteria
Criteria
Inclusion Criteria:
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All twins will be required to give written informed consent.
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Subjects will be included with a history of Vietnam Era service.
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All subjects must be free of major medical illness on the basis of history and physical examination, lab testing, and electrocardiogram.
Exclusion Criteria:
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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.
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Subjects will also be excluded if based on the SCID interview they have comorbid:
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schizophrenia;
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schizoaffective disorder;
-
bulimia or anorexia, or
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bipolar disorder.
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Subjects will also be excluded with a history of blast injury with associated traumatic brain injury.
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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.
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Atlanta VA Medical and Rehab Center, Decatur | Decatur | Georgia | United States | 30033 |
Sponsors and Collaborators
- US Department of Veterans Affairs
Investigators
- Principal Investigator: Doug Bremner, MD, Atlanta VA Medical and Rehab Center, Decatur
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- MHBA-008-07S
Study Results
Participant Flow
| Recruitment Details | Subjects recruited through Vietnam Era Twin Registry 2001-2012. |
|---|---|
| Pre-assignment Detail | Subjects studied at baseline with no interventions. |
| Arm/Group Title | Group 1 |
|---|---|
| Arm/Group Description | Vietnam veterans who were twins with and without posttraumatic stress disorder underwent neuropsychological testing and MRI imaging of hippocampal volume at baseline. There were no clinical interventions. |
| Period Title: Overall Study | |
| STARTED | 142 |
| COMPLETED | 142 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Group 1 |
|---|---|
| Arm/Group Description | Vietnam veterans who were twins with and without posttraumatic stress disorder underwent neuropsychological testing and MRI imaging of hippocampal volume at baseline. There were no clinical interventions. |
| Overall Participants | 142 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
142
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
53
(2)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
142
100%
|
| Region of Enrollment (participants) [Number] | |
| United States |
142
100%
|
Outcome Measures
| Title | Neuropsychological Testing of Memory |
|---|---|
| Description | Percent retention on the Wechsler Memory Scale - Logical |
| Time Frame | 2 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Vietnam Veteran Twins |
|---|---|
| Arm/Group Description | Vietnam veteran twins with and without PTSD. |
| Measure Participants | 142 |
| PTSD |
77
(14)
|
| non PTSD |
82
(15)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Vietnam Twins With and Without PTSD | |
| Arm/Group Description | ||
All Cause Mortality |
||
| Vietnam Twins With and Without PTSD | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Vietnam Twins With and Without PTSD | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/142 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Vietnam Twins With and Without PTSD | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/142 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | J Douglas Bremner MD |
|---|---|
| Organization | Atlanta VAMC |
| Phone | 404-712-9569 |
| jdbremn@emory.edu |
- MHBA-008-07S