PT  - JOURNAL ARTICLE
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
TI  - Hippocampal subfield volumes are uniquely affected in PTSD and depression: International analysis of 31 cohorts from the PGC-ENIGMA PTSD Working Group
AID  - 10.1101/739094
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 739094
4099  - http://biorxiv.org/content/early/2019/08/21/739094.short
4100  - http://biorxiv.org/content/early/2019/08/21/739094.full
AB  - 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.