Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm
Authors: Jiang Yuchao , Luo Cheng , Wang Jijun , Palaniyappan Lena , Chang Xiao , Xiang Shitong , Zhang Jie , Duan Mingjun , Huang Huan , Gaser Christian , Nemoto Kiyotaka , Miura Kenichiro , Hashimoto Ryota , Westlye Lars T. , Richard Genevieve , Fernandez-Cabello Sara , Parker Nadine , Andreassen Ole A. , Kircher Tilo , Nenadić Igor , Stein Frederike , Thomas-Odenthal Florian , Teutenberg Lea , Usemann Paula , Dannlowski Udo , Hahn Tim , Grotegerd Dominik , Meinert Susanne , Lencer Rebekka , Tang Yingying , Zhang Tianhong , Li Chunbo , Yue Weihua , Zhang Yuyanan , Yu Xin , Zhou Enpeng , Lin Ching-Po , Tsai Shih-Jen , Rodrigue Amanda L. , Glahn David , Pearlson Godfrey , Blangero John , Karuk Andriana , Pomarol-Clotet Edith , Salvador Raymond , Fuentes-Claramonte Paola , Garcia-León María Ángeles , Spalletta Gianfranco , Piras Fabrizio , Vecchio Daniela , Banaj Nerisa , Cheng Jingliang , Liu Zhening , Yang Jie , Gonul Ali Saffet , Uslu Ozgul , Burhanoglu Birce Begum , Uyar Demir Aslihan , Rootes-Murdy Kelly , Calhoun Vince D. , Sim Kang , Green Melissa , Quidé Yann , Chung Young Chul , Kim Woo-Sung , Sponheim Scott R. , Demro Caroline , Ramsay Ian S. , Iasevoli Felice , de Bartolomeis Andrea , Barone Annarita , Ciccarelli Mariateresa , Brunetti Arturo , Cocozza Sirio , Pontillo Giuseppe , Tranfa Mario , Park Min Tae M. , Kirschner Matthias , Georgiadis Foivos , Kaiser Stefan , Van Rheenen Tamsyn E. , Rossell Susan L. , Hughes Matthew , Woods William , Carruthers Sean P. , Sumner Philip , Ringin Elysha , Spaniel Filip , Skoch Antonin , Tomecek David , Homan Philipp , Homan Stephanie , Omlor Wolfgang , Cecere Giacomo , Nguyen Dana D. , Preda Adrian , Thomopoulos Sophia I. , Jahanshad Neda , Cui Long-Biao , Yao Dezhong , Thompson Paul M. , Turner Jessica A. , van Erp Theo G. M. , Cheng Wei ,   ENIGMA Schizophrenia Consortium, de Bartolomeis Andrea , Van Rheenen Tamsyn E. , Feng Jianfeng ,   ZIB Consortium
Published: July 2024

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal ‘trajectory’ of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.