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- Title
Posttraumatic Stress Disorder and Advanced Aging.
- Authors
Burnison, Erik
- Abstract
Introduction: Posttraumatic stress disorder (PTSD) is a condition of chronic psychological stress that has been shown through both genetic and physiologic research modalities to be associated with accelerated cellular aging and, therefore, earlier onset of age-related disease, neurodegeneration, and premature mortality. However, the relationship between PTSD and neuroanatomical aging is not well understood. This study examined MRI scans to determine whether PTSD is associated with advanced aging. Through techniques yet to be utilized with PTSD, Brain-Age Regression Analysis and Computation Utility Software (BARACUS), this study determined participants brain age relative to their chronological age thus further confirming the impact of this disorder on brain health as well as providing a useful clinical and research metric that may assist in diagnosing PTSD as well as personalizing therapeutic strategy. Methods: MRI data were drawn from 94 veterans as part of a previously published fMRI study. Participants (85 men, nine women) were aged 21-45. Other data collected include ethnicity (primarily white), PTSD, depression, alcohol use, and military history. Exclusion criteria included: 1) report of a traumatic brain injury based on the Traumatic Brain Injury Checklist; 2) contraindications to MRI (e.g., claustrophobia, metal in the body); and 3) current crisis-related issues such as a serious self-injurious behavior, psychosis, or substance dependence (excluding alcohol dependence). T1-weighted MRI images were processed through FreeSurfer 5.3.0 “recon-all” pipeline to generate statistics files for cortical thickness, surface area, and subcortical volume region. These data were then used as input to a trained model, BARACUS, which utilizes linear support regression models to estimate each participant’s brain age. Results: Having PCL-M (PTSD) scores of greater than 30 was associated with advanced predicted brain aging (higher predicted brain age relative to chronological age). The predicted brain age minus chronological age, known as the predicted brain age difference (PBAD) was 4.4 years for the PTSD group versus 0.3 years for the control group. This association remained after controlling for significant covariates such as depression, alcohol consumption, general health, and military history. Conclusions: Through use of BARACUS, we were able to determine a statistically significant difference in predicted brain age between those with high PTSD symptomatology and those without. Genetic and physiologic studies support this through strong evidence that chronic stress leads to accelerated cellular aging. Predicted brain age difference (PBAD) is a simple, single composite score that can act as an assumed biomarker representing complex interactions that may not be fully captured in the traditional analysis of multiple regions of interest. Considering these algorithms are developed from cross-sectional data, at any given age, one would expect a normal distribution of morphometric variation that could be due to neurological insult, congenital conditions (e.g., chromosome abnormalities), psychological insult, or simply normal heterogeneity. To this end, researchers should be cautious in the interpretation of this new biomarker, discussing the deviations in predicted brain age rather than interpreting advanced predicted brain age as reflecting an “older brain.” To better characterize what is being measured, future neuroimaging-based age predictions may benefit from incorporating other physiological measures such as magnetoencephalography and electroencephalography as well as combining with cellular and molecular age prediction assessments such as telomere and methylation approaches.
- Subjects
POST-traumatic stress disorder; CELLULAR aging; AGE; BRAIN injuries; SELF-injurious behavior; AGE differences
- Publication
South Dakota Medicine, 2019, Vol 72, Issue 9, p398
- ISSN
0038-3317
- Publication type
Academic Journal