Delin Sun, Duke University
Gopalkumar Rakesh, Duke University
Courtney C. Haswell, Duke University
Mark Logue, Boston University School of Medicine
C. Lexi Baird, Duke University
Erin N. O'Learly, University of Toledo
Andrew S. Cotton, University of Toledo
Hong Xie, University of Toledo
Marijo Tamburrino, University of Toledo
Tian Chen, University of Toledo
Emily L. Dennis, University of Southern California
Neda Jahanshad, University of Southern California
Lauren Salminen, University of Southern California
Sophia I. Thomopoulos, University of Southern California
Faisal Rashid, University of Southern California
Christopher R.K. Ching, University of Southern California
Saskia B.J. Koch, University of Amsterdam
Jessie L. Frijling, Amsterdam University Medical Centers
Laura Nawijn, Amsterdam University Medical Centers
Mirjam Van Zuiden, Amsterdam University Medical Centers
Xi Zhu, Columbia University
Benjamin Suarez-Jimenez, Columbia University Medical Center
Anika Sierk, University Medical Centre Charite
Henrik Walter, University Medical Centre Charite
Antje Manthey, University Medical Centre Charite
Jennifer S. Stevens, Emory University
Negar Fani, Emory University School of Medicine
Sanne J.H. Van Rooij, Emory University School of Medicine
Murray Stein, University of California - San Diego
Jessica A. Bomyea, University of Southern California - San Diego
Inga K. Koerte, Brigham and Women's Hospital
Kyle Choi, University of California - San Diego
Steven J.A. van der Werff, Leiden University
Robert R.J.M. Vermeiren, Leiden University
Julia Herzog, Heidelberg University
Lauren A. M. Lebois, Harvard Medical School
Justin T. Baker, Harvard University McLean Hospital
Elizabeth A. Olson, Harvard Medical School, McLean Hospital
Thomas Straube, University of Muenster
Mayuresh S. Korgaonkar, University of Sydney
Elpiniki Andrew, University of Sydney
Ye Zhu, University of Chinese Academy of Sciences
Gen Li, University of Chinese Academy of Sciences
Jonathan Ipser, University of Cape Town
Anna R. Hudson, Ghent University
Matthew Peverill, University of Washington
Kelly Sambrook, University of Washington
Evan Gordon, Washington University - St. Louis
Lee A. Baugh, University of South Dakota
Gina L. Forster, University of Otago
Raluca M. Simons, University of South Dakota
Jeffrey S. Simons, University of South Dakota
Vincent A. Magnotta, University of Iowa
Adi Maron-Katz, Stanford University of Medicine
Stefan du Plessis, Stanford University
Seth Disner, University of Minnesota Medical School
Nicholas Davenport, University of Minnesota Medical School
Daniel W. Grupe, University of Wisconsin - Madison
Jack B. Nitschke, University of Wisconsin - Madison
Terri A. deRoon-Cassini, Medical College of Wisconsin
Jacklynn M. Fitzgerald, Marquette UniversityFollow
John H. Krystal, National Center for PTSD
Ifat Levy, National Center for PTSD
Miranda Olff, ARQ National Psychotrauma Centrum
Dick J. Veltman, Amsterdam University Medical Centers
Li Wang, University of Chinese Academy of Sciences
Yuval Neria, Columbia University Medical Center
Michael D. De Bellis, Duke University
Tanja Jovanovic, Wayne State University
Judith K. Daniels, University of Groningen
Martha E. Shenton, Harvard Medical School
Nic J.A. van de Wee, Leiden University Medical Center
Christian Schmahl, Heidelberg University
Milissa L. Kaufman, McLean Hospital
Isabelle M. Rosso, Harvard Medical School
Scott R. Sponheim, University of Minnesota
David Hofmann, University of Muenster
Richard A. Bryant, University of New South Wales
Kelene A. Fercho, University of South Dakota
Dan J. Stein, University of Cape Town
Sven C. Mueller, Ghent University
Bobak Hosseini, University of Illinois at Chicago
K. Luan Phan, University of Illinois at Chicago
Katie A. McLaughlin, Harvard University
Richard J. Davidson, University of Wisconsin - Milwaukee
Christine L. Larson, University of Wisconsin - Milwaukee
Geoffrey May, Baylor University
Steven M. Nelson, Baylor University
Chadi G. Abdallah, National Center for PTSD
Hassaan Gomaa, Pennsylvania State University
Amit Etkin, Stanford University of Medicine
Soraya Seedat, Stellenbosch University
Ilan Harpaz-Rotem, National Center for PTSD
Israel Liberzon, Texas A&M University
Theo G.M. van Erp, University of California Irvine
Yann Quidé, University of New South Wales
Xin Wang, University of Toledo
Paul M. Thompson, University of Southern California
Rajendra A. Morey, Duke University

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Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.


Accepted Version. Neurolmage, Vol. 261, No. 1(November 2022): 119509. DOI © 2022 ScienceDirect. Used with permission.

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