Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder

作者：Leonardo Cardoso Saraiva, João Ricardo Sato, Isaac Sebenius, Nadža Džinalija, Carla del Río-Torné, Fábio Godinho, Antônio Carlos Lopes, Thomas Fernandez, Monicke O. Lima, Vanessa do Nascimento Ramos, Ricardo Iglesias, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Ana Isabel Araújo, Paul Arnold, Srinivas Balachander, Nerisa Banaj, Marcelo C. Batistuzzo, Francesco Benedetti, Irene Bollettini, B. Bravi, Brian P. Brennan, Jan Buitelaar, Miguel Castelo‐Branco, Sunah Choi, Ana D. Costa, Sara Dallaspezia, Damiaan Denys, Isabel Catarina Duarte, Marco Antonio Nocito Echevarria, Goi Khia Eng, Afonso Fernandes, Jamie D. Feusner, Martijn Figee, Sophie Fitzsimmons, Leonardo F. Fontenelle, Rachael Grazioplene, Minji Ha, Alejandro Hinojosa‐Corona, Marcelo Q. Hoexter, Chaim Huijser, Hao Hu, Anthony James, Minah Kim, Jun Soo Kwon, Luisa Lazaro, Christine Löchner, Mafalda Machado-Sousa, Hein van Marle, Ignacio Martínez‐Zalacaín, David Mataix‐Cols, José M. Menchón, Luciano Minuzzi, Pedro Morgado, Emma Muñoz‐Moreno, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Joseph O’Neill, In‐Kyung Park, Mary L. Phillips, John Piacentini, Maria Picó-Pérez, Fabrizio Piras, Federica Piras, Tjardo Postma, Chiang-shan R. Li, Janardhan Y. C. Reddy, Daan van Rooij, Yuki Sakai, Juliana Braga de Salles Andrade, Freda Scheffler, Venkataram Shivakumar, Noam Soreni, Emily Stern, Anouk van der Straten, Sophia I. Thomopoulos, Hirofumi Tomiyama, Fernanda Tovar‐Moll, Daniela Vecchio, Dick J. Veltman, Ganesan Venkatasubramanian, Chris Vriend, Zhen Wang, Ysbrand D. van der Werf, Guido van Wingen, Qing Zhao, ENIGMA-OCD Working Group, Carla del Río-Torné, Sara Bertolín, Jan Buitelaar, João Castelhano, Tiago Lemos Cerqueira, Patrícia Coelho, Beatriz Couto, Ana D. Costa, Afonso Fernandes, Sónia Ferreira, Jonathan Ipser, Taekwan Kim, Luisa Lazaro, Wieke van Leeuwen, Mafalda Machado-Sousa, Hein van Marle, Maria E. de Mathis, Elisa Melloni, Luciano Minuzzi, Pedro Moreira, Pedro Morgado, Ástrid Morer, Laurens A. van de Mortel, Takashi Nakamae, Jin Narumoto, Harin Oh, Ana E. Ortiz, Maria Picó-Pérez, Sara Poletti, Chiang-shan R. Li, Eva Real, Daan van Rooij, Cinto Segalàs, Nuno Sousa, Anouk van der Straten, Jinsong Tang, Anri Watanabe, Ysbrand D. van der Werf, Guido van Wingen, Kei Yamada, Dan J. Stein, Odile A. van den Heuvel, Christopher Pittenger, Alexander W. Charney, Youngsun Cho, Roseli Gedanke Shavitt, Helen Pushkarskaya, Carles Soriano‐Mas, Rafael Romero-Garcia, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Anderson M. Winkler, Euripedes C. Miguel Filho, Christopher Pittenger, Carolina Cappi · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-74153-2 · 被引用次数：1 · 研究领域：Obsessive-Compulsive Spectrum Disorders

Studies of brain morphology in mental illness often focus on a few neuroimaging phenotypes. Here we present a comprehensive morphological characterization in obsessive-compulsive disorder (OCD) in a large sample (2255 OCD, 2264 controls) using nine cortical and four subcortical phenotypes, including several not previously examined in OCD, among them a subcortical structural similarity network phenotype developed here. Spatially distinct regional alterations emerged across structural phenotypes: cortical curvature alterations in default mode and frontoparietal networks, increased structural similarity network node degree in sensorimotor regions, widespread volume reductions associated with medication use, and localized subcortical shape alterations. In brain-behavior predictive models, curvature phenotypes showed the strongest associations with clinical features. Cortical alterations, especially in structural similarity networks, were associated with specific gene expression patterns, implicating dysregulation of excitatory neurons. RNA-sequencing data from tissue collected during functional neurosurgery revealed that genes downregulated in the dorsolateral prefrontal cortex in OCD contributed to the gene expression patterns linked to cortical alterations. Previously reported differentially expressed genes from postmortem brain studies of OCD also contributed. These findings support the importance of a comprehensive approach to characterizing brain morphology and suggest that ...