Murray B Stein1, Esther Yuh2, Sonia Jain3, David O Okonkwo4, Christine L Mac Donald5, Harvey Levin6, Joseph T Giacino7, Sureyya Dikmen5, Mary J Vassar8, Ramon Diaz-Arrastia9, Claudia S Robertson6, Lindsay D Nelson10, Michael McCrea10, Xiaoying Sun3, Nancy Temkin5, Sabrina R Taylor8, Amy J Markowitz11, Geoffrey T Manley8, Pratik Mukherjee2. 1. Department of Psychiatry, University of California San Diego, La Jolla, California; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California; VA San Diego Healthcare System, San Diego, California. Electronic address: mstein@health.ucsd.edu. 2. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California. 3. Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California. 4. Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 5. Department of Neurological Surgery, University of Washington, Seattle, Washington. 6. Department of Neurosurgery, Baylor College of Medicine, Houston, Texas. 7. Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts; Spaulding Rehabilitation Hospital, Charlestown, Massachusetts. 8. Department of Neurological Surgery, University of California San Francisco, San Francisco, California; Brain and Spinal Cord Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California. 9. Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania. 10. Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin. 11. Brain and Spinal Cord Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California. Electronic address: amymarkowitz@gmail.com.
Abstract
BACKGROUND: Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. METHODS: Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. RESULTS: Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. CONCLUSIONS: Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury. Published by Elsevier Inc.
BACKGROUND: Brain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury. METHODS: Using data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices. RESULTS: Overall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors. CONCLUSIONS: Results, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury. Published by Elsevier Inc.
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