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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 Alnæs, 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 D. Calhoun, Erick J Canales-Rodriguez, Dara Cannon, Xavier Caseras, Tiffany Chaim-Avancini, Francisco X. Castellanos, Tiffany M. Chaim-Avancini, Christopher R.K. Ching, Vincent P. Clark, Patricia J. Conrod, Annette Conzelmann, Fabrice Crivello, Christopher G. Davey, Erin W. Dickie, Stefan Ehrlich, Dennis van 't Ent, Simon E. 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 Hartman, Sean N Hatton, Dirk J. Heslenfeld, Odile A. van den Heuvel, Ian B Hickie, Pieter J. Hoekstra, Sarah Hohmann, Avram J Holmes, Martine Hoogman, Norbert Hosten, Fleur M. Howells, Hilleke E. Hulshoff Pol, Chaim Huyser, Neda Jahanshad, Anthony C James, Jiyang Jiang, Erik G Jonsson, John A Joska, Andrew J. Kalnin, Karolinska Schizophrenia Project (KaSP) Consortium, Marieke Klein, Laura Koenders, Knut K Kolskar, Bernd Kramer, Jonna Kuntsi, Jim Lagopoulos, Luisa Lazaro, Irina S Lebedeva, Phil H. Lee, Christine Lochner, Marise WJ Machielsen, Sophie Maingault, Nicholas G Martin, Ignacio Martinez-Zalacain, David Mataix-Cols, Bernard Mazoyer, Brenna C McDonald, Colm McDonald, A.M McIntosh, Katie L. McMahon, Genevieve McPhilemy, Dennis van der Meer, Jose M Menchon, 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 Sarro, 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 J. Veltman, Aristotle Voineskos, Henry Volzke, Henrik Walter, Lei Wang, Yang Wang, Bernd Weber, Wei Wen, John D West, Lars T. Westlye, H.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

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 patterns of greater male than female between-subject variance for all brain 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.

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