Individualized Structural Brain Deviations in Bipolar I Disorder: a Normative Modeling Study of 4 660 ENIGMA Participants
Abstract
Abstract Bipolar disorder (BD) is a prevalent psychiatric condition characterized by marked clinical and neuroanatomical heterogeneity. Prior neuroimaging studies have used case-control comparisons yielding small to moderate effect sizes for group differences. Large and diverse samples are needed to map heterogeneity within BD. Here, we used individualized brain morphometry deviations derived from normative modeling for three MRI-based measures (regional cortical thickness, regional surface area, and subcortical volumes). We applied this approach to a large international sample of 4 660 individuals (1 145 with bipolar I disorder and 3 515 healthy controls) from the ENIGMA Bipolar Disorder Working Group consortium (age range = 8–80, female = 53.15%) and examined the distribution of deviations within the bipolar disorder group, differences between healthy controls and individuals with bipolar disorder, and associations between neuroanatomical deviations and clinical variables. We found that individuals with bipolar disorder showed a higher proportion of localized extreme deviations, notably negative cortical thickness deviations in regions consistently reported as thinner in prior studies (the left superior frontal gyrus, bilateral inferior frontal gyrus (pars opercularis), left precuneus) and subcortical volume negative deviations in the left hippocampus. In addition, ROI-level deviations in the left middle temporal gyrus and the left inferior temporal gyrus were associated with longer illness duration. This is the largest study to date exploring individualized deviations as neuroanatomical features associated with bipolar disorder. Our findings suggest that neuroanatomical heterogeneity is a core feature of bipolar disorder, with preferential left-lateralized cortical-hippocampal involvement pointing to spatially structured heterogeneity.
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Authors: Nathan Neu, Pauline Favre, Édouard Duchesnay, Melody Kang, Yanghee Im, Neda Jahanshad, Paul M. Thompson, Christopher Ching, Nadine Parker, Lars Tjelta Westlye, Dag Alnæs, Melissa J. Green, Yann Quidé, Matthew D. Sacchet, Ian H. Gotlib, Kang Sim, Gloria Roberts, Janice Fullerton, Bronwyn J. Overs, Philip Bowden Mitchell, Kody G. Kennedy, Benjamin I. Goldstein, Bradley J. MacIntosh, Erick Jorge Canales-Rodríguez, Edith Pomarol‐Clotet, Raymond M. Salvador, Enric Vilajosana, Joaquim Raduà, Eduard Vieta, Francesco Benedetti, Elisa Maria Teresa Melloni, Beatrice Bravi, Tamsyn E. Van Rheenen, Susan Rossel, Colm McDonald, Leila Nabulsi, Dara M. Cannon, Theodore Satterthwaite, Dominik Grotegerd, Eva Mennigen, Tim Hahn, Sabrina Teckentrup, Sara Papenbrock, Tilo T. J. Kircher, Roberto Goya‐Maldonado, Monica Di Giuliano, Godfrey D. Pearlson, David C. Glahn, Amanda Rodrigue, James J. Prisciandaro, Fabio Sambataro, Annabella Di Girogio, Bartholomeus C. M. Haarman, Jair C. Soares, Giovana Zunta Soares, Benson Mwangi, Mon‐Ju Wu, Pedro Rosa, Geraldo Busatto, Maurício Henriques Serpa, Marcus V. Zanetti, Tiffany Avancini, Hilary P. Blumberg, Lejla Čolić, Mikael Landén, Anna Luisa Klahn, Dan Stein, Freda Scheffler, Fleur Margaret Howells, Henk S. Temmingh, Lakshmi N. Yatham, Ezgi Key, Ali Saffet Gönül, Mehmet Cagdas Eker, Ole A. Andreasson, Josselin Houenou, Charles Laidi, Udo Dannlowski, Andriana Karuk
Institutions: University of British Columbia, Universidade de São Paulo, The University of Melbourne, Harvard University, Universitätsmedizin Göttingen, UNSW Sydney, University of Southern California, Inserm, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Yale University, Stanford University, University of Münster, University of Cape Town, Philipps University of Marburg, University of Oslo, University of Gothenburg, Universitat de Barcelona, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sunnybrook Hospital, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Ollscoil na Gaillimhe – University of Galway, Jena University Hospital, CEA Paris-Saclay, Vita-Salute San Raffaele University, Medical University of South Carolina, King's College London, Boston Children's Hospital, École Polytechnique Fédérale de Lausanne, The University of Texas Health Science Center at Houston, Institute of Mental Health, Neuroscience Research Australia, IRCCS Ospedale San Raffaele, CEA Paris-Saclay - Etablissement de Saclay, Fidmag Sisters Hospitallers