Lifespan brain structural variation reveals shared organization across mental health conditions

作者：Meike Dorothee Hettwer, Amin Saberi, Golia Shafiei, Aikaterina Manoli, Augustijn A. A. de Boer, Dag Alnæs, Pino Alonso, Celso Arango, Michal Assaf, Mihai Avram, Srinivas Balachander, Nerisa Banaj, Zeynep Başgöze, Marcelo C. Batistuzzo, Stéphanie Bauduin, Francesco Benedetti, Sara Bertolín, Bianca Besteher, Laura Biagi, Robert J. Blair, Karina Blair, Sven Bölte, Stefan Borgwardt, Paolo Bosco, Paolo Brambilla, Beatrice Bravi, Brian P. Brennan, Willem B. Bruin, Geraldo F. Busatto, Murray J. Cairns, Sara Calderoni, Vince D. Calhoun, Rosa Calvo, Marta Cano, V. J. Carr, Sean P. Carruthers, Georgia F Caruana, Xavier Caseras, Stanley V. Catts, I‐Jou Chi, Derin J. Cobia, Federica Colombo, Maria Beatriz Couto, Benedicto Crespo-Facorro, Kathryn R. Cullen, Udo Dannlowski, Mirella Dapretto, Adriana Di Martino, Gretchen J. Diefenbach, Annemiek Dols, Fabio Duran, Nadža Džinalija, Christine Ecker, Stefan Ehrlich, Goi Khia Eng, Damien A. Fair, Afonso Fernandes, Jamie D. Feusner, Gregory A. Fonzo, Paola Fuentes‐Claramonte, Nadine Gaab, Beata R. Godlewska, Benjamin I. Goldstein, Ali Saffet Gonul, Ian H. Gotlib, Hans J. Grabe, Melissa J. Green, Dominik Grotegerd, Oliver Gruber, Patricia Gruner, Abha R. Gupta, Ruben C. Gur, Raquel E. Gur, Shlomi Haar, Jarold P. Hamilton, Unn Kristin Haukvik, Frans A. Henskens, Asli C. Hinc, Yoshiyuki Hirano, Hao Hu, Matthew E. Hughes, Felice Iasevoli, Yanghee Im, Jonathan Ipser, Hammza Jabbar Abdl Sattar Hamoudi, Allison Jack, Delfina Janiri, Joost Janssen, Fern Jaspers‐Fayer, Kyle M. Jensen, Jingwen Jin, Stefan Kaiser, Toshiharu Kamishikiryo, Melody J. Y. Kang, Andriana Karuk, Norbert Kathmann, Kody G. Kennedy, Minah Kim, Joseph A. King, Tilo Kircher, Anna Luisa Klahn, Daniel N. Klein, Kathrin Koch, Peter V Kochunov, Azadeh Kushki, Jun Soo Kwon, Marilyn T. Lake, Mikael Landén, Luisa Lázaro, Irina Lebedeva, Nabulsi Leila, Meng Li, Christine Löchner, Carmel M. Loughland, Beatriz Luna, Karl Lundin Remnélius, Bradley John MacIntosh, Matteo Mancini, Gisele Gus Manfro, Rachel Marsh, Ignacio Martinez-Zalacain, David Mataix-Cols, Colm McDonald, Jane McGrath, Jose M. Menchon, Pedro Figueiredo Morgado, Bryan J. Mowry, Lilianne Rivka Mujica-Parodi, Emma Muñoz, Filippo Muratori, Declan Murphy, Benson Mwangi, Janardhanan C. Narayanaswamy, Jin Narumoto, Stener Nerland, Janina Neufeld, Benjamin T. Newman, Jared Allen Nielsen, Erika L. Nurmi, Joseph O`Neill, Kirsten M. O’Hearn, Go Okada, Bob Oranje, Christos Pantelis, Nadine Parker, Kevin A. Pelphrey, Mary L. Phillips, John Piacentini, Maria Picó‐Pérez, Rosanne Picotin, Alessandro Pigoni, Fabrizio Piras, Federica Piras, Edith Pomarol-Clotet, Giuseppe Pontillo, Daniel Porta-Casteràs, María J Portella, Rebecca B. Price, Yann Quidé, Joaquim Radua, Elysha Ringin, Elena Rodríguez‐Cano, Jaroslav Rokicki, Rafael Romero-Garcia, Susan Rossell, Hanyang Ruan, Katya Rubia, Matthew D. Sacchet, Yuki Sakai, Raymond Salvador, Gabriele Sani, João R. Sato, André Schmidt, Rodney J. Scott, Carl M. Sellgren, Lukas Sempach, Eiji Shimizu, Venkataram Shivakumar, Kang Sim, Jair C. Soares, Noam Soreni, Carles Soriano‐Mas, Nuno Sousa, Frederike Stein, Jonas L. Steinhäuser-Meerz, Emily R. Stern, Thomas Straube, Jeffrey R. Strawn, Philip J. Sumner, Ibrahim Sungur, Philip R. Szeszko, Kristiina Tammimies, Alexander S. Tomyshev, Michela Tosetti, Laurens A. van de Mortel, John D. Van Horn, Helena van Nieuwenhuizen, Tamsyn E. Van Rheenen, Guido Alexander van Wingen, Daniela Vecchio, Ganesan Venkatasubramanian, Eduard Vieta, Enric Vilajosana, Yolanda Vives-Gilabert, Henry Völzke, Chris Vriend, Gregory L. Wallace, Zhen Wang, Martin Walter, Lei Wang, Sara Jane Webb, Lars Tjelta Westlye, Sarah Whittle, Mark O. Wielpütz, Katharina Wittfeld, Will Woods, Mon-Ju Wu, Tony T. Yang, Lakshmi N. Yatham, Tokiko Yoshida, Abe Yoshinari, Je‐Yeon Yun, Qing Zhao, Giovana B. Zunta‐Soares, ENIGMA Autism Working Group, ENIGMA Anxiety Working Group, ENIGMA Bipolar Disorder Working Group, ENIGMA Major Depression Working Group, ENIGMA OCD Working Group, ENIGMA Schizophrenia Working Group, Odile A. van den Heuvel, Lianne Schmaal, Elena Pozzi, Ole A. Andreassen, Christopher R. K. Ching, Katherine E. Lawrence, Gaon S. Kim, Jan K. Buitelaar, Theo G.M. van Erp, Dan J. Stein, Daniel S. Pine, Anderson M. Winkler, Janna Marie Bas‐Hoogendam, André Zugman, Nic J.A. van der Wee, Nynke A. Groenewold, Andre Marquand, Boris C. Bernhardt, Neda Jahanshad, Tyler M. Moore, Paul M. Thompson, Sophia I. Thomopoulos, Simon B Eickhoff, Matthias Kirschner, Theodore Daniel Satterthwaite, Sofie Louise Valk · 发表于：medRxiv · 年份：2026 · DOI：10.64898/2026.08.13.26360304 · 被引用次数：1 · 研究领域：Functional Brain Connectivity Studies、Schizophrenia research and treatment、Genetic Associations and Epidemiology

Abstract Elucidating the neurobiological basis of neurodevelopmental and psychiatric conditions (NDPCs) remains challenging because brain alterations vary within diagnoses and overlap across them. Whether diverse alterations follow a systematic organization that may reflect shared vulnerabilities remains unknown. Here, we assembled 10,135 individuals with schizophrenia, autism, bipolar, obsessive-compulsive, generalized anxiety, and major depressive disorders, and 11,998 reference participants across six continents through the ENIGMA consortium. Using normative modeling, we quantified individual deviations in cortical thickness, surface area, and subcortical volumes relative to lifespan reference trajectories (5 to 80 years). We show that structural deviations converged along cortical axes reflecting connectome organization, maturation, and cytoarchitectonic diversity. These axes mirrored typical population variation, but their expression differed across diagnoses and partly scaled with symptom severity. Even rare and highly individualized extreme deviations followed this organization, concentrating in densely connected regions. Finally, brain structural deviations overlapped substantially across diagnoses, while differences between them increased toward the association cortex. Together, we provide large-scale evidence that structural deviations across NDPCs are systematically constrained by the brain’s intrinsic architecture. This shared organization provides a framework for...