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Greater male than female variability in regional brain structure across the lifespan

By Lara M Wierenga, Gaelle E. Doucet, Danai Dima, Ingrid Agartz, Moji Aghajani, Theophilus N Akudjedu, Anton Albajes-Eizagirre, Dag Alnaes, Kathryn I Alpert, Ole A. Andreassen, Alan Anticevic, Philip Asherson, Tobias Banaschewski, Nuria Bargallo, Sarah Baumeister, Ramona Baur-Streubel, Alessandro Bertolino, Aurora Bonvino, Dorret I Boomsma, Stefan Borgwardt, Josiane Bourque, Anouk den Braber, Daniel Brandeis, Alan Breier, Henry Brodaty, Rachel M Brouwer, Jan K. Buitelaar, Geraldo F Busatto, Vince Calhoun, Erick J Canales-Rodriguez, Dara M. Cannon, Xavier Caseras, F. Xavier Castellanos, Tiffany M Chaim-Avancini, Alan C. Ching, Vincent P Clark, Patricia J. Conrod, Annette Conzelmann, Fabrice Crivello, Christopher G. Davey, Erin W. Dickie, Stefan Ehrlich, Dennis van ’t Ent, SE Fisher, Jean-Paul Fouche, Barbara Franke, Paola Fuentes-Claramonte, Eco JC de Geus, Annabella Di Giorgio, David C Glahn, Ian H. Gotlib, Hans J Grabe, Oliver Gruber, Patricia Gruner, Raquel E. Gur, Ruben C. Gur, Tiril P Gurholt, Lieuwe de Haan, Beathe Haatveit, Ben J Harrison, Catharina A Hartman, Sean N Hatton, Dirk J. Heslenfeld, Odile A. van den Heuvel, Ian B Hickie, Pieter Hoekstra, Sarah Hohmann, Avram Holmes, Martine Hoogman, Norbert Hosten, Fleur M Howells, Hilleke Hulshoff Pol, Chaim Huyser, Neda Jahanshad, Anthony C James, Jiyang Jiang, Erik G. Jönsson, John A Joska, Andrew J Kalnin, Karolinska Schizophrenia Project (KaSP) Consortium, Marieke Klein, Laura Koenders, Knut K. Kolskår, Bernd Krämer, Jonna Kuntsi, Jim Lagopoulos, Luisa Lazaro, Irina S Lebedeva, Phil H Lee, Christine Lochner, Marise WJ Machielsen, Sophie Maingault, Nicholas G Martin, Ignacio Martínez-Zalacaín, David Mataix-Cols, Bernard Mazoyer, Brenna C McDonald, Colm McDonald, Andrew M McIntosh, Katie L. McMahon, Genevieve McPhilemy, Dennis van der Meer, José M Menchón, Jilly Naaijen, Lars Nyberg, Jaap Oosterlaan, Yannis Paloyelis, Paul Pauli, Giulio Pergola, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Andreas Reif, Geneviève Richard, Joshua L. Roffman, Pedro G.P. Rosa, Matthew D. Sacchet, Perminder S. Sachdev, Raymond Salvador, Salvador Sarró, Theodore D. Satterthwaite, Andrew J Saykin, Mauricio H. Serpa, Kang Sim, Andrew Simmons, Jordan W. Smoller, Iris E Sommer, Carles Soriano-Mas, Dan J. Stein, Lachlan T Strike, Philip R. Szeszko, Henk S Temmingh, Sophia I Thomopoulos, Alexander S Tomyshev, Julian N. Trollor, Anne Uhlmann, Ilya M. Veer, Dick Veltman, Aristotle Voineskos, Henry Völzke, Henrik Walter, Lei Wang, Yang Wang, Bernd Weber, Wei Wen, John D West, Lars T. Westlye, Heather C. Whalley, Steven CR Williams, Katharina Wittfeld, Daniel H Wolf, Margaret J Wright, Yuliya N. Yoncheva, Marcus V. Zanetti, Georg C. Ziegler, Greig I de Zubicaray, Paul M. Thompson, Eveline A. Crone, Sophia Frangou, Christian K Tamnes

Posted 17 Feb 2020
bioRxiv DOI: 10.1101/2020.02.17.952010 (published DOI: 10.1002/hbm.25204)

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders. ### Competing Interest Statement The authors declare the following competing interests: OAA: Speakers honorarium from Lundbeck, Consultant of HealthLyti; PA: Received payments for consultancy to Shire/Takeda, Medic, educational/research awards from Shire/Takeda, GW Pharma, Janssen-Cila, speaker at sponsored events for Shire, Flynn Pharma, Medic; TB: advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm, conference support or speakers fee by Lilly, Medice, and Shire, received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press - the present work is unrelated to the above grants and relationship; DB: serves as an unpaid scientific consultant for an EU-funded neurofeedback trial that is unrelated to the present work; HB: Advisory Board, Nutricia Australi; CRKC: received partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript; BF: received educational speaking fees from Medice; HJG: received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care; NJ and PMT: MPI of a research related grant from Biogen, Inc., for research unrelated to the contents of this manuscript; JK: given talks at educational events sponsored by Medic; all funds are received by Kings College London and used for studies of ADHD; DM-C: receives fees from UpToDate, Inc and Elsevier, all unrelated to the current work; AMM: received research support from Eli Lilly, Janssen, and the Sackler Foundation, and speaker fees from Illumina and Janssen; DJS: received research grants and/or honoraria from Lundbeck and Sun. The remaining authors declare no competing interests.

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