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

AbstractBackgroundPTSD 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.MethodsWe 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.ResultsA 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.ConclusionsCollectively 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.