Estimating multimodal brain variability in schizophrenia spectrum disorders: A worldwide ENIGMA study
Authors: Omlor Wolfgang , Rabe Finn , Fuchs Simon , Cecere Giacomo , Homan Stephanie , Surbeck Werner , Kallen Nils , Georgiadis Foivos , Spiller Tobias , Seifritz Erich , Weickert Thomas , Bruggemann Jason , Weickert Cynthia , Potkin Steven , Hashimoto Ryota , Sim Kang , Rootes-Murdy Kelly , Quide Yann , Houenou Josselin , Banaj Nerisa , Vecchio Daniela , Piras Fabrizio , Piras Federica , Spalletta Gianfranco , Salvador Raymond , Karuk Andriana , Pomarol-Clotet Edith , Rodrigue Amanda , Pearlson Godfrey , Glahn David , Tomecek David , Spaniel Filip , Skoch Antonin , Kirschner Matthias , Kaiser Stefan , Kochunov Peter , Fan Feng-Mei , Andreassen Ole A. , Westlye Lars T. , Berthet Pierre , Calhoun Vince D , Howells Fleur , Uhlmann Anne , Scheffler Freda , Stein Dan , Iasevoli Felice , Cairns Murray J. , Carr Vaughan J. , Catts Stanley V. , Di Biase Maria A. , Jablensky Assen , Green Melissa J. , Henskens Frans A. , Klauser Paul , Loughland Carmel , Michie Patricia T. , Mowry Bryan , Pantelis Christos , Rasser Paul E. , Schall Ulrich , Scott Rodney , Zalesky Andrew , de Bartolomeis Andrea , Barone Annarita , Ciccarelli Mariateresa , Brunetti Arturo , Cocozza Sirio , Pontillo Giuseppe , Tranfa Mario , Di Giorgio Annabella , Thomopoulos Sophia I. , Jahanshad Neda , Thompson Paul M. , van Erp Theo , Turner Jessica , Homan Philipp 
Published: September 2023

Objective

Schizophrenia is a multifaceted disorder associated with structural brain heterogeneity. Despite its relevance for identifying illness subtypes and informative biomarkers, structural brain heterogeneity in schizophrenia remains incompletely understood. Therefore, the objective of this study was to provide a comprehensive insight into the structural brain heterogeneity associated with schizophrenia.

Methods

This meta- and mega-analysis investigated the variability of multimodal structural brain measures of white and gray matter in individuals with schizophrenia versus healthy controls. Using the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6139 individuals for a given brain measure, we examined variability in cortical thickness, surface area, folding index, subcortical volume and fractional anisotropy.

Results

We found that individuals with schizophrenia are distinguished by higher heterogeneity in the frontotemporal network with regard to multimodal structural measures. Moreover, individuals with schizophrenia showed higher homogeneity of the folding index, especially in the left parahippocampal region.

Conclusions

Higher multimodal heterogeneity in frontotemporal regions potentially implies different subtypes of schizophrenia that converge on impaired frontotemporal interaction as a core feature of the disorder. Conversely, more homogeneous folding patterns in the left parahippocampal region might signify a consistent characteristic of schizophrenia shared across subtypes. These findings underscore the importance of structural brain variability in advancing our neurobiological understanding of schizophrenia, and aid in identifying illness subtypes as well as informative biomarkers.