Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group
Authors: Salminen Lauren E. , Sämann Philipp G. , Zheng Yuanchao , Dennis Emily L. , Clarke-Rubright Emily K. , Jahanshad Neda , Iglesias Juan E. , Whelan Christopher D. , Bruce Steven E. , Hayes Jasmeet P. , Seedat Soraya , Averill Christopher L. , Baugh Lee A. , Bomyea Jessica , Bright Joanna , Buckle Chanellé J. , Choi Kyle , Davenport Nicholas D. , Davidson Richard J. , Densmore Maria , Disner Seth G. , du Plessis Stefan , Elman Jeremy A. , Fani Negar , Forster Gina L. , Franz Carol E. , Frijling Jessie L. , Gonenc Atilla , Gruber Staci A. , Grupe Daniel W. , Guenette Jeffrey P. , Haswell Courtney C. , Hofmann David , Hollifield Michael , Hosseini Babok , Hudson Anna R. , Ipser Jonathan , Jovanovic Tanja , Kennedy-Krage Amy , Kennis Mitzy , King Anthony , Kinzel Philipp , Koch Saskia B. J. , Koerte Inga , Koopowitz Sheri M. , Korgaonkar Mayuresh S. , Kremen William S. , Krystal John , Lebois Lauren A. M. , Levy Ifat , Lyons Michael J. , Magnotta Vincent A. , Manthey Antje , Nakahara Soichiro , Nawijn Laura , Neufeld Richard W. J. , Nitschke Jack B. , O’Doherty Daniel C. M. , Paul Robert H. , Peverill Matthew , Rashid Faisal M. , Ressler Kerry J. , Roos Annerine , Schmahl Christian , Sheridan Margaret A. , Sierk Anika , Simmons Alan N. , Simons Jeffrey S. , Simons Raluca M. , Stein Murray B. , Stevens Jennifer S. , Suarez-Jimenez Benjamin , Théberge Jean , Thomaes Kathleen , Thomopoulos Sophia I. , van den Heuvel Leigh L. , van der Werff Steven J. A. , van Erp Theo G. M. , van Rooij Sanne J. H. , van Zuiden Mirjam , Varkevisser Tim , Vermeiren Robert R. J. M. , Wager Tor D. , Walter Henrik , Wang Xin , Winternitz Sherry , Wolff Jonathan D. , Wrocklage Kristen , Zhu Xi , Ching Christopher R. K. , Gurholt Tiril P. , Haukvik Unn K. , Agartz Ingrid , Abdallah Chadi G. , Bryant Richard , Daniels Judith K. , DeBellis Michael , Fercho Kelene A. , Geuze Elbert , Harpaz-Rotem Ilan , Herzog Julia I. , Kaufman Milissa L. , Lagopoulos Jim , Lanius Ruth A. , McLaughlin Katie A. , Mueller Sven C. , Neria Yuval , Olff Miranda , Phan K. Luan , Shenton Martha E. , Sponheim Scott R. , Stein Dan J. , Straube Thomas , van der Wee Nic J. A. , Veltman Dick J. , Thompson Paul M. , Morey Rajendra A. , Logue Mark W. ,   for the ENIGMA-PGC-PTSD Working Group
Published: August 2019

Background

PTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression.

Methods

We used random effects regressions and a harmonized neuroimaging protocol based on FreeSurfer (v6.0) to identify sub-structural hippocampal markers of current PTSD (C-PTSD), depression, and the interaction of these conditions across 31 cohorts worldwide (N=3,115;Mage=38.9±13.9 years). Secondary analyses tested these associations by sex and after modeling the simultaneous effects of remitted PTSD, childhood trauma, mild traumatic brain injury, and alcohol use disorder.

Results

A significant negative main effect of depression (n=800, vs. no depression, n=1456) was observed in the hippocampal tail (ß=−0.13) and CA1 (ß=−0.09) after adjusting for covariates and multiple testing (adjusted p’s (q)=0.028). A main effect of C-PTSD (n=1042 vs. control, n=1359) was not significant, but an interaction between C-PTSD and depression was significant in the CA1 (ß=−0.24, q=0.044). Pairwise comparisons revealed significantly smaller CA1 volumes in individuals with C-PTSD+Depression than controls (ß=−0.12, q=0.012), C-PTSD-only (ß=−0.17, q=0.001), and Depression-only (ß=−0.18, q=0.023). Follow-up analyses revealed sex effects in the hippocampal tail of depressed females, and an interaction effect of C-PTSD and depression in the fimbria of males.

Conclusions

Collectively our results suggest that depression is a stronger predictor of hippocampal volumetry than PTSD, particularly in the CA1, and provide compelling evidence of more pronounced hippocampal phenotypes in comorbid PTSD and depression compared to either condition alone.