The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium

Bruin, W. B.; Abe, Y.; Alonso, P.; Anticevic, A.; Backhausen, L. L.; Balachander, S.; Bargallo, N.; Batistuzzo, M. C.; Benedetti, F.; Bertolin Triquell, S.; Brem, S.; Calesella, F.; Couto, B.; Denys, D. A. J. P.; Echevarria, M. A. N.; Eng, G. K.; Ferreira, S.; Feusner, J. D.; Grazioplene, R. G.; Gruner, P.; Guo, J. Y.; Hagen, K.; Hansen, B.; Hirano, Y.; Hoexter, M. Q.; Jahanshad, N.; Jaspers-Fayer, F.; Kasprzak, S.; Kim, M.; Koch, K.; Bin Kwak, Y.; Kwon, J. S.; Lazaro, L.; C. -S. R., Li; Lochner, C.; Marsh, R.; Martinez-Zalacain, I.; Menchon, J. M.; Moreira, P. S.; Morgado, P.; Nakagawa, A.; Nakao, T.; Narayanaswamy, J. C.; Nurmi, E. L.; Zorrilla, J. C. P.; Piacentini, J.; Pico-Perez, M.; Piras, F.; Piras, F.; Pittenger, C.; Reddy, J. Y. C.; Rodriguez-Manrique, D.; Sakai, Y.; Shimizu, E.; Shivakumar, V.; Simpson, B. H.; Soriano-Mas, C.; Sousa, N.; Spalletta, G.; Stern, E. R.; Evelyn Stewart, S.; Szeszko, P. R.; Tang, J.; Thomopoulos, S. I.; Thorsen, A. L.; Tokiko, Y.; Tomiyama, H.; Vai, B.; Veer, I. M.; Venkatasubramanian, G.; Vetter, N. C.; Vriend, C.; Walitza, S.; Waller, L.; Wang, Z.; Watanabe, A.; Wolff, N.; Yun, J. -Y.; Zhao, Q.; van Leeuwen, W. A.; van Marle, H. J. F.; van de Mortel, L. A.; van der Straten, A.; van der Werf, Y. D.; Bin Kwak, Y.; Pariente Zorrilla, J. C.; Stewart, S. E.; van Leeuwen, W. A.; van Marle, H. J. F.; van de Mortel, L. A.; van der Straten, A.; van der Werf, Y. D.; van den Heuvel, O. A.; van Wingen, G. A.; Thompson, P. M.; Stein, D. J.; van den Heuvel, O. A.; van Wingen, G. A.

doi:10.1038/s41380-023-02077-0

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen’s d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen’s d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium / Bruin, W. B.; Abe, Y.; Alonso, P.; Anticevic, A.; Backhausen, L. L.; Balachander, S.; Bargallo, N.; Batistuzzo, M. C.; Benedetti, F.; Bertolin Triquell, S.; Brem, S.; Calesella, F.; Couto, B.; Denys, D. A. J. P.; Echevarria, M. A. N.; Eng, G. K.; Ferreira, S.; Feusner, J. D.; Grazioplene, R. G.; Gruner, P.; Guo, J. Y.; Hagen, K.; Hansen, B.; Hirano, Y.; Hoexter, M. Q.; Jahanshad, N.; Jaspers-Fayer, F.; Kasprzak, S.; Kim, M.; Koch, K.; Bin Kwak, Y.; Kwon, J. S.; Lazaro, L.; Li, C. -S. R.; Lochner, C.; Marsh, R.; Martinez-Zalacain, I.; Menchon, J. M.; Moreira, P. S.; Morgado, P.; Nakagawa, A.; Nakao, T.; Narayanaswamy, J. C.; Nurmi, E. L.; Zorrilla, J. C. P.; Piacentini, J.; Pico-Perez, M.; Piras, F.; Piras, F.; Pittenger, C.; Reddy, J. Y. C.; Rodriguez-Manrique, D.; Sakai, Y.; Shimizu, E.; Shivakumar, V.; Simpson, B. H.; Soriano-Mas, C.; Sousa, N.; Spalletta, G.; Stern, E. R.; Evelyn Stewart, S.; Szeszko, P. R.; Tang, J.; Thomopoulos, S. I.; Thorsen, A. L.; Tokiko, Y.; Tomiyama, H.; Vai, B.; Veer, I. M.; Venkatasubramanian, G.; Vetter, N. C.; Vriend, C.; Walitza, S.; Waller, L.; Wang, Z.; Watanabe, A.; Wolff, N.; Yun, J. -Y.; Zhao, Q.; van Leeuwen, W. A.; van Marle, H. J. F.; van de Mortel, L. A.; van der Straten, A.; van der Werf, Y. D.; Bin Kwak, Y.; Pariente Zorrilla, J. C.; Stewart, S. E.; van Leeuwen, W. A.; van Marle, H. J. F.; van de Mortel, L. A.; van der Straten, A.; van der Werf, Y. D.; van den Heuvel, O. A.; van Wingen, G. A.; Thompson, P. M.; Stein, D. J.; van den Heuvel, O. A.; van Wingen, G. A.. - In: MOLECULAR PSYCHIATRY. - ISSN 1359-4184. - (2023). [Epub ahead of print] [10.1038/s41380-023-02077-0]