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Brain Amygdala Volume Increases in Veterans and Active-Duty Military Personnel With Combat-Related Posttraumatic Stress Disorder and Mild Traumatic Brain Injury

Pieper, Joel MD; Chang, Douglas G. MD, PhD; Mahasin, Sarah Z. MBBS, MAS; Swan, Ashley Robb BA; Quinto, Annemarie Angeles BA; Nichols, Sharon L. PhD; Diwakar, Mithun MD, PhD; Huang, Charles BS; Swan, James BS; Lee, Roland R. MD; Baker, Dewleen G. MD; Huang, Mingxiong PhD

The Journal of Head Trauma Rehabilitation: April 25, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/HTR.0000000000000492
Original Article: PDF Only

Objective: To identify amygdalar volumetric differences associated with posttraumatic stress disorder (PTSD) in individuals with comorbid mild traumatic brain injury (mTBI) compared with those with mTBI-only and to examine the effects of intracranial volume (ICV) on amygdala volumetric measures.

Setting: Marine Corps Base and VA Healthcare System.

Participants: A cohort of veterans and active-duty military personnel with combat-related mTBI (N = 89).

Design: Twenty-nine participants were identified with comorbid PTSD and mTBI. The remaining 60 formed the mTBI-only control group. Structural images of brains were obtained with a 1.5-T MRI scanner using a T1-weighted 3D-IR-FSPGR pulse sequence. Automatic segmentation was performed in Freesurfer.

Main Measures: Amygdala volumes with/without normalizations to ICV.

Results: The comorbid mTBI/PTSD group had significantly larger amygdala volumes, when normalized to ICV, compared with the mTBI-only group. The right and left amygdala volumes after normalization to ICV were 0.122% ± 0.012% and 0.118% ± 0.011%, respectively, in the comorbid group compared with 0.115% ± 0.012% and 0.112% ± 0.009%, respectively, in the mTBI-only group (corrected P < .05).

Conclusions: The ICV normalization analysis performed here may resolve previous literature discrepancies. This is an intriguing structural finding, given the role of the amygdala in the challenging neuroemotive symptoms witnessed in casualties of combat-related mTBI and PTSD.

Department of Physical Medicine and Rehabilitation University of Michigan, Ann Arbor, Michigan (Dr Pieper), Departments of Orthopaedic Surgery (Dr Chang), Radiology, Research, and Psychiatry Services (Mss Swan and Quinto and Drs Lee, Baker, and M. Huang), Radiology (Mss Swan and Quinto and Drs Lee and M. Huang), Neurosciences (Dr Nichols), and Psychiatry (Dr Baker), University of California, San Diego; College of Medicine, King Saud University, Riyadh, Saudi Arabia (Ms Mahasin); Department of Radiology and Biomedical Imaging, University of California, San Francisco (Dr Diwakar); Department of Bioengineering, Stanford University, Stanford, California (Mr C. Huang); Department of Management Information Systems, San Diego State University, San Diego, California (Mr Swan); and VA Center of Excellence for Stress and Mental Health, San Diego, California (Dr Baker).

Corresponding Author: Mingxiong Huang, PhD, Radiology Imaging Laboratory, University of California San Diego, 3510 Dunhill St, San Diego, CA 92121 (

Portions of this work were presented in poster form at the fourth annual Sports Concussion Conference, American Academy of Neurology, Jacksonville, Florida, July 14-16, 2017.

This work was supported in part by Merit Review Grants from the Department of Veterans Affairs (I01-CX000499, MHBA-010-14F, I01-RX001988, B1988-I, NURC-022-10F, and NEUC-044-06S) and Naval Medical Research Center's Advanced Medical Development program (Naval Medical Logistics Command Contract #N62645-11-C-4037, for MRS-II). This research was also supported by the NIH Short Term Research Training Grant (NHLBI) T35 HL007491. The authors thank staff at the VA Healthcare System and the Veterans Medical Research Foundation (VRMF). The authors also thank the participating military and veteran volunteers for their military service and participation in this study, as well as the University of California, San Diego, Health Sciences International program for their support.

The authors declare no conflicts of interest.

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