TY - JOUR T1 - Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group JF - bioRxiv DO - 10.1101/739094 SP - 739094 AU - Lauren E. Salminen AU - Philipp G. Sämann AU - Yuanchao Zheng AU - Emily L. Dennis AU - Emily K. Clarke-Rubright AU - Neda Jahanshad AU - Juan E. Iglesias AU - Christopher D. Whelan AU - Steven E. Bruce AU - Jasmeet P. Hayes AU - Soraya Seedat AU - Christopher L. Averill AU - Lee A. Baugh AU - Jessica Bomyea AU - Joanna Bright AU - Chanellé J. Buckle AU - Kyle Choi AU - Nicholas D. Davenport AU - Richard J. Davidson AU - Maria Densmore AU - Seth G. Disner AU - Stefan du Plessis AU - Jeremy A. Elman AU - Negar Fani AU - Gina L. Forster AU - Carol E. Franz AU - Jessie L. Frijling AU - Atilla Gonenc AU - Staci A. Gruber AU - Daniel W. Grupe AU - Jeffrey P. Guenette AU - Courtney C. Haswell AU - David Hofmann AU - Michael Hollifield AU - Babok Hosseini AU - Anna R. Hudson AU - Jonathan Ipser AU - Tanja Jovanovic AU - Amy Kennedy-Krage AU - Mitzy Kennis AU - Anthony King AU - Philipp Kinzel AU - Saskia B. J. Koch AU - Inga Koerte AU - Sheri M. Koopowitz AU - Mayuresh S. Korgaonkar AU - William S. Kremen AU - John Krystal AU - Lauren A. M. Lebois AU - Ifat Levy AU - Michael J. Lyons AU - Vincent A. Magnotta AU - Antje Manthey AU - Soichiro Nakahara AU - Laura Nawijn AU - Richard W. J. Neufeld AU - Jack B. Nitschke AU - Daniel C. M. O’Doherty AU - Robert H. Paul AU - Matthew Peverill AU - Faisal M. Rashid AU - Kerry J. Ressler AU - Annerine Roos AU - Christian Schmahl AU - Margaret A. Sheridan AU - Anika Sierk AU - Alan N. Simmons AU - Jeffrey S. Simons AU - Raluca M. Simons AU - Murray B. Stein AU - Jennifer S. Stevens AU - Benjamin Suarez-Jimenez AU - Jean Théberge AU - Kathleen Thomaes AU - Sophia I. Thomopoulos AU - Leigh L. van den Heuvel AU - Steven J. A. van der Werff AU - Theo G. M. van Erp AU - Sanne J. H. van Rooij AU - Mirjam van Zuiden AU - Tim Varkevisser AU - Robert R. J. M. Vermeiren AU - Tor D. Wager AU - Henrik Walter AU - Xin Wang AU - Sherry Winternitz AU - Jonathan D. Wolff AU - Kristen Wrocklage AU - Xi Zhu AU - Christopher R. K. Ching AU - Tiril P. Gurholt AU - Unn K. Haukvik AU - Ingrid Agartz AU - Chadi G. Abdallah AU - Richard Bryant AU - Judith K. Daniels AU - Michael DeBellis AU - Kelene A. Fercho AU - Elbert Geuze AU - Ilan Harpaz-Rotem AU - Julia I. Herzog AU - Milissa L. Kaufman AU - Jim Lagopoulos AU - Ruth A. Lanius AU - Katie A. McLaughlin AU - Sven C. Mueller AU - Yuval Neria AU - Miranda Olff AU - K. Luan Phan AU - Martha E. Shenton AU - Scott R. Sponheim AU - Dan J. Stein AU - Thomas Straube AU - Nic J. A. van der Wee AU - Dick J. Veltman AU - Paul M. Thompson AU - Rajendra A. Morey AU - Mark W. Logue AU - for the ENIGMA-PGC-PTSD Working Group Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/21/739094.abstract N2 - 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. ER -