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Cited by 24Traumatic Brain Injury ResearchPosttraumatic Stress Disorder ResearchTraumatic Brain Injury and Neurovascular Disturbances

Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months After Mild Traumatic Brain Injury

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Stein, Murray B., Yuh, Esther, Jain, Sonia, Okonkwo, David O., Mac Donald, Christine L., Levin, Harvey, Giacino, Joseph T., Dikmen, Sureyya +63 more·2021·Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
DOI 10.1016/j.bpsc.2020.10.008PMC PMC7946719
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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.

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  • Smaller cortical volumes of superior frontal cortex and rostral and caudal cingulate at 2 weeks after trauma contributed to the prediction of increased likelihood of 3-month PTSD diagnosis in multivariable models incorporating other established risk factors.

    “In another study recruiting patients after trauma exposure with mild traumatic brain injury, smaller cortical volumes of superior frontal cortex and rostral and caudal cingulate at 2 weeks after trauma exposure contributed to the prediction of increased likelihood of 3-month PTSD diagnosis in multivariable models incorporating other established risk factors [158].”

    From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [158]

    The Results report that smaller superior frontal and rostral and caudal anterior cingulate volumes at two weeks predicted PTSD status at three months in fully adjusted models. However, the Methods define the outcome as probable PTSD based on a PCL-5 score, not a confirmed clinical diagnosis. (LLM, conf=0.85)

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Authors
Stein, M. B., Yuh, E., Jain, S., Okonkwo, D. O., Mac Donald, C. L., Levin, H., Giacino, J. T., Dikmen, S., Vassar, M. J., Diaz-Arrastia, R., Robertson, C. S., Nelson, L. D., McCrea, M., Sun, X., Temkin, N., Taylor, S. R., Markowitz, A. J., Manley, G. T., Mukherjee, P., Adeoye, O., Badjatia, N., Boase, K., Barber, J., Bodien, Y., Bullock, M. R., Chesnut, R., Corrigan, J. D., Crawford, K., Duhaime, A.-C., Ellenbogen, R., Feeser, V. R., Ferguson, A. R., Foreman, B., Gardner, R., Gaudette, E., Goldman, D., Gonzalez, L., Gopinath, S., Gullapalli, R., Hemphill, J. C., Hotz, G., Jain, S., Keene, C. D., Korley, F. K., Kramer, J., Kreitzer, N., Lindsell, C., Machamer, J., Madden, C., Martin, A., McAllister, T., Merchant, R., Ngwenya, L. B., Noel, F., Nolan, A., Palacios, E., Perl, D., Puccio, A., Rabinowitz, M., Robertson, C., Rosand, J., Sander, A., Satris, G., Schnyer, D., Seabury, S., Toga, A., Valadka, A., Vespa, P., Wang, K., Yue, J. K., & Zafonte, R.
Affiliations
  • University of California San Diego (US)
  • University of California, San Francisco (US)
  • University of Pittsburgh Medical Center (US)
  • Baylor College of Medicine (US)
  • Harvard University (US)
  • University of Washington (US)
  • San Francisco General Hospital (US)
  • University of Pennsylvania (US)
  • Medical College of Wisconsin (US)
Corresponding author
  • Stein, Murray B.
  • Markowitz, Amy J.
ORCID
Venue
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Publisher
Elsevier BV
Published
2021-03
Volume
6
Issue
3
Pages
352-359
ISSN
2451-9022 (ISSN-L)
DOI
10.1016/j.bpsc.2020.10.008
PMC
PMC7946719
OpenAlex
W3096917732
Cited by
24
References
5
Citations by year
2026: 1 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 5 · 2021: 4
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry Cognitive Neuroscience and Neuroimaging (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • University of Southern California
  • University of Pittsburgh
  • Vanderbilt University
  • University of Cincinnati
  • University of Miami
  • University of Maryland
  • Harvard Medical School (62/269,778)
  • Baylor College of Medicine
  • Massachusetts General Hospital
  • University of California, San Diego
  • U.S. Department of Energy
  • University of Michigan
  • National Institute of Neurological Disorders and Stroke
  • University of Florida
  • Abbott Laboratories
  • University of Washington
  • Amgen
  • ACADIA Pharmaceuticals
  • GE Healthcare
  • Avanir Pharmaceuticals
  • U.S. Department of Defense (W81XWH-14-2-0176)
  • Ohio State University
  • National Football League Players Association
  • National Institutes of Health (U01NS086090)
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
post-traumatic stress disorder, mild traumatic brain injury, regional brain volume, PTSD risk prediction, hippocampus, amygdala, insula, anterior cingulate cortex, orbitofrontal cortex, superior frontal cortex, TRACK-TBI
MeSH terms
Amygdala, Brain, Brain Concussion, Hippocampus, Humans, Stress Disorders, Post-Traumatic

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