DenseNet and Support Vector Machine classifications of major depressive disorder using vertex-wise cortical features

18 Nov 2023 · Vladimir Belov, Tracy Erwin-Grabner, Ling-Li Zeng, Christopher R. K. Ching, Andre Aleman, Alyssa R. Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Katharina Brosch, Robin Bülow, Romain Colle, Colm G. Connolly, Emmanuelle Corruble, Baptiste Couvy-Duchesne, Kathryn Cullen, Udo Dannlowski, Christopher G. Davey, Annemiek Dols, Jan Ernsting, Jennifer W. Evans, Lukas Fisch, Paola Fuentes-Claramonte, Ali Saffet Gonul, Ian H. Gotlib, Hans J. Grabe, Nynke A. Groenewold, Dominik Grotegerd, Tim Hahn, J. Paul Hamilton, Laura K. M. Han, Ben J Harrison, Tiffany C. Ho, Neda Jahanshad, Alec J. Jamieson, Andriana Karuk, Tilo Kircher, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Ramona Leenings, Meng Li, David E. J. Linden, Frank P. MacMaster, David M. A. Mehler, Susanne Meinert, Elisa Melloni, Bryon A. Mueller, Benson Mwangi, Igor Nenadić, Amar Ojha, Yasumasa Okamoto, Mardien L. Oudega, Brenda W. J. H. Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J. Portella, Elena Pozzi, Joaquim Radua, Elena Rodríguez-Cano, Matthew D. Sacchet, Raymond Salvador, Anouk Schrantee, Kang Sim, Jair C. Soares, Aleix Solanes, Dan J. Stein, Frederike Stein, Aleks Stolicyn, Sophia I. Thomopoulos, Yara J. Toenders, Aslihan Uyar-Demir, Eduard Vieta, Yolanda Vives-Gilabert, Henry Völzke, Martin Walter, Heather C. Whalley, Sarah Whittle, Nils Winter, Katharina Wittfeld, Margaret J. Wright, Mon-Ju Wu, Tony T. Yang, Carlos Zarate, Dick J. Veltman, Lianne Schmaal, Paul M. Thompson, Roberto Goya-Maldonado ·

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used globally representative data from the ENIGMA-MDD working group containing an extensive sample of people with MDD (N=2,772) and HC (N=4,240), which allows a comprehensive analysis with generalizable results. Based on the hypothesis that integration of vertex-wise cortical features can improve classification performance, we evaluated the classification of a DenseNet and a Support Vector Machine (SVM), with the expectation that the former would outperform the latter. As we analyzed a multi-site sample, we additionally applied the ComBat harmonization tool to remove potential nuisance effects of site. We found that both classifiers exhibited close to chance performance (balanced accuracy DenseNet: 51%; SVM: 53%), when estimated on unseen sites. Slightly higher classification performance (balanced accuracy DenseNet: 58%; SVM: 55%) was found when the cross-validation folds contained subjects from all sites, indicating site effect. In conclusion, the integration of vertex-wise morphometric features and the use of the non-linear classifier did not lead to the differentiability between MDD and HC. Our results support the notion that MDD classification on this combination of features and classifiers is unfeasible.

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