Smaller hippocampal CA1 subfield volume in posttraumatic stress disorder

Lyon W. CHEN, Delin SUN, Sarah L. DAVIS, Courtney C. HASWELL, Emily L. DENNIS, Chelsea A. SWANSON, Christopher D. WHELAN, Boris GUTMAN, Neda JAHANSHAD, Juan Eugenio IGLESIAS, Paul THOMPSON, Mid-Atlantic MIRECC Workgroup, H. Ryan WAGNER, Philipp SAEMANN, Kevin S. LABAR, Rajendra A. MOREY

Research output: Contribution to journalArticlespeer-review

39 Citations (Scopus)


Background: Smaller hippocampal volume in patients with posttraumatic stress disorder (PTSD) represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD-associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features. 

Methods: Case-control cross-sectional studies of U.S. military veterans (n = 282) from the Iraq and Afghanistan era were grouped into PTSD (n = 142) and trauma-exposed controls (n = 140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3 T. Segmentation with FreeSurfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, DG, fimbria, fissure, hippocampus-amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model. 

Results: Significantly lower subfield volumes were associated with PTSD in left CA1 (P = 0.01; d = 0.21; uncorrected), CA3 (P = 0.04; d = 0.08; uncorrected), and right CA3 (P = 0.02; d = 0.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. A trend level association of L-CA1 with PTSD (F4, 221= 3.32, P = 0.07) is present and the other subfield findings are nonsignificant if ipsilateral whole hippocampal volume is not included as a covariate. PTSD-associated differences in global hippocampal shape were nonsignificant. 

Conclusions: The present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety-like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories. Copyright © 2018 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)1018-1029
JournalDepression and Anxiety
Issue number11
Early online dateSept 2018
Publication statusPublished - Nov 2018


Chen, L. W., Sun, D., Davis, S. L., Haswell, C. C., Dennis, E. L., Swanson, C. A., . . . Morey, R. A. (2018). Smaller hippocampal CA1 subfield volume in posttraumatic stress disorder. Depression and Anxiety, 35(11), 1018-1029. doi: 10.1002/da.22833


Dive into the research topics of 'Smaller hippocampal CA1 subfield volume in posttraumatic stress disorder'. Together they form a unique fingerprint.