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Stability of hippocampal subfield volumes after trauma and relationship to development of PTSD symptoms. Neuroimage 2021 Aug 01;236:118076



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Scopus ID

2-s2.0-85104960391 (requires institutional sign-in at Scopus site)   14 Citations


BACKGROUND: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus' functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0.

METHODS: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability.

RESULTS: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl - T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure.

CONCLUSION: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).

Author List

Weis CN, Webb EK, Huggins AA, Kallenbach M, Miskovich TA, Fitzgerald JM, Bennett KP, Krukowski JL, deRoon-Cassini TA, Larson CL


Carissa W. Tomas PhD Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Terri A. deRoon Cassini PhD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cross-Sectional Studies
Longitudinal Studies
Magnetic Resonance Imaging
Middle Aged
Reproducibility of Results
Severity of Illness Index
Stress Disorders, Post-Traumatic
Wounds and Injuries
Young Adult