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

Willem B. Bruin; Yoshinari Abe; Pino Alonso; Alan Anticevic; Lea L. Backhausen; Srinivas Balachander; Nuria Bargallo; Marcelo C. Batistuzzo; Francesco Benedetti; Sara Bertolin Triquell; Silvia Brem; Federico Calesella; Beatriz Couto; Damiaan A.J.P. Denys; Marco A.N. Echevarria; Goi Khia Eng; Sónia Ferreira; Jamie D. Feusner; Rachael G. Grazioplene; Patricia Gruner; Joyce Y. Guo; Kristen Hagen; Bjarne Hansen; Yoshiyuki Hirano; Marcelo Q. Hoexter; Neda Jahanshad; Fern Jaspers-Fayer; Selina Kasprzak; Minah Kim; Kathrin Koch; Yoo Bin Kwak; Jun Soo Kwon; Luisa Lazaro; Chiang Shan R. Li; Christine Lochner; Rachel Marsh; Ignacio Martínez-Zalacaín; Jose M. Menchon; Pedro S. Moreira; Pedro Morgado; Akiko Nakagawa; Tomohiro Nakao; Janardhanan C. Narayanaswamy; Erika L. Nurmi; Jose C.Pariente Zorrilla; John Piacentini; Maria Picó-Pérez; Fabrizio Piras; Federica Piras; Christopher Pittenger; Janardhan Y.C. Reddy; Daniela Rodriguez-Manrique; Yuki Sakai; Eiji Shimizu; Venkataram Shivakumar; Blair H. Simpson; Carles Soriano-Mas; Nuno Sousa; Gianfranco Spalletta; Emily R. Stern; S. Evelyn Stewart; Philip R. Szeszko; Jinsong Tang; Sophia I. Thomopoulos; Anders L. Thorsen; Tokiko Yoshida; Hirofumi Tomiyama; Benedetta Vai; Ilya M. Veer; Ganesan Venkatasubramanian; Nora C. Vetter; Chris Vriend; Susanne Walitza; Lea Waller; Zhen Wang; Anri Watanabe; Nicole Wolff; Je Yeon Yun; Qing Zhao; Wieke A. van Leeuwen; Hein J.F. van Marle; Laurens A. van de Mortel; Anouk van der Straten; Ysbrand D. van der Werf; Honami Arai; Irene Bollettini; Rosa Calvo Escalona; Ana Coelho; Federica Colombo; Leila Darwich; Martine Fontaine; Toshikazu Ikuta; Jonathan C. Ipser; Asier Juaneda-Seguí; Hitomi Kitagawa; Gerd Kvale; Mafalda Machado-Sousa; Astrid Morer; Takashi Nakamae; Jin Narumoto; Joseph O’Neill; Sho Okawa; Eva Real; Veit Roessner; Joao R. Sato; Cinto Segalàs; Roseli G. Shavitt; Dick J. Veltman; Kei Yamada; Wieke A. van Leeuwen; Hein J.F. van Marle; Laurens A. van de Mortel; Anouk van der Straten; Ysbrand D. van der Werf; Odile A. van den Heuvel; Guido A. van Wingen; Paul M. Thompson; Dan J. Stein; Odile A. van den Heuvel; Guido A. van Wingen

doi:10.1038/s41380-023-02077-0

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

Willem B. Bruin^*, Yoshinari Abe, Pino Alonso, Alan Anticevic, Lea L. Backhausen, Srinivas Balachander, Nuria Bargallo, Marcelo C. Batistuzzo, Francesco Benedetti, Sara Bertolin Triquell, Silvia Brem, Federico Calesella, Beatriz Couto, Damiaan A.J.P. Denys, Marco A.N. Echevarria, Goi Khia Eng, Sónia Ferreira, Jamie D. Feusner, Rachael G. Grazioplene, Patricia GrunerJoyce Y. Guo, Kristen Hagen, Bjarne Hansen, Yoshiyuki Hirano, Marcelo Q. Hoexter, Neda Jahanshad, Fern Jaspers-Fayer, Selina Kasprzak, Minah Kim, Kathrin Koch, Yoo Bin Kwak, Jun Soo Kwon, Luisa Lazaro, Chiang Shan R. Li, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, Jose M. Menchon, Pedro S. Moreira, Pedro Morgado, Akiko Nakagawa, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Jose C.Pariente Zorrilla, John Piacentini, Maria Picó-Pérez, Fabrizio Piras, Federica Piras, Christopher Pittenger, Janardhan Y.C. Reddy, Daniela Rodriguez-Manrique, Yuki Sakai, Eiji Shimizu, Venkataram Shivakumar, Blair H. Simpson, Carles Soriano-Mas, Nuno Sousa, Gianfranco Spalletta, Emily R. Stern, S. Evelyn Stewart, Philip R. Szeszko, Jinsong Tang, Sophia I. Thomopoulos, Anders L. Thorsen, Tokiko Yoshida, Hirofumi Tomiyama, Benedetta Vai, Ilya M. Veer, Ganesan Venkatasubramanian, Nora C. Vetter, Chris Vriend, Susanne Walitza, Lea Waller, Zhen Wang, Anri Watanabe, Nicole Wolff, Je Yeon Yun, Qing Zhao, Wieke A. van Leeuwen, Hein J.F. van Marle, Laurens A. van de Mortel, Anouk van der Straten, Ysbrand D. van der Werf, Honami Arai, Irene Bollettini, Rosa Calvo Escalona, Ana Coelho, Federica Colombo, Leila Darwich, Martine Fontaine, Toshikazu Ikuta, Jonathan C. Ipser, Asier Juaneda-Seguí, Hitomi Kitagawa, Gerd Kvale, Mafalda Machado-Sousa, Astrid Morer, Takashi Nakamae, Jin Narumoto, Joseph O’Neill, Sho Okawa, Eva Real, Veit Roessner, Joao R. Sato, Cinto Segalàs, Roseli G. Shavitt, Dick J. Veltman, Kei Yamada, Wieke A. van Leeuwen, Hein J.F. van Marle, Laurens A. van de Mortel, Anouk van der Straten, Ysbrand D. van der Werf, Odile A. van den Heuvel, Guido A. van Wingen^*, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Guido A. van Wingen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	4307-4319
Number of pages	13
Journal	Molecular Psychiatry
Volume	28
Issue number	10
DOIs	https://doi.org/10.1038/s41380-023-02077-0
State	Published - Oct 2023
Externally published	Yes

Funding

Funders	Funder number
Agència de Gestió d'Ajuts Universitaris i de Recerca
South African Medical Research Council
Spanish Ministry of Universities
Fondo de Investigaciones Sanitarias
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Michael Smith Health Research BC
Biogen
Heidehof Stiftung
Ministero della Salute
Obsessive-Compulsive Foundation
Government of India
Brain and Behavior Research Foundation
National Alliance for Research on Schizophrenia and Depression
National Research Foundation
European Regional Development Fund
International OCD Foundation
Japan Agency for Medical Research and Development	JP22dm0307002, JP22dm0307008
National Natural Science Foundation of China	81871057, 82171495, 82071518
Clinical and Public Health Research Center	IA/CRC/19/1/610005
National Institute on Aging Research Project	R01AG058854
Japan Society for the Promotion of Science	21K07547, 22K15766, 19K03309, 18K15523, 22H01090, 16K04344, 21K03084, 22K07598
Department of Science and Technology, Ministry of Science and Technology, India	IFA12-LSBM-26, SR/S0/HS/0016/2011
AUGUR	2017SGR 1247
Netherlands Brain Foundation	2010(1
Instituto de Salud Carlos III	CM21/00278, PI18/00856
Helse Vest Health Authority	911754, 911880
Fundació la Marató de TV3	091810
Department of Biotechnology, Ministry of Science and Technology, India	BT/ PR13334/Med/30/259/2009, BT/06/IYBA/2012
European Commission	MAZ/2021/11
Hartmann Müller-Stiftung für Medizinische Forschung	1460
IRCCS Fondazione Santa Lucia	RC19-20-21-22/A
Deutsche Forschungsgemeinschaft	VE 892/2-1, KO 3744/11-1
Conselho Nacional de Desenvolvimento Científico e Tecnológico	303754/2018-4
Consejería de Salud y Familias, Junta de Andalucía	PI11/01419
Key Technologies Research and Development Program	2022YFE0103700
National Institute of Neurological Disorders and Stroke	RO1NS107513
Fundação para a Ciência e a Tecnologia	UIDP/50026/2020, UIDB/50026/2020, NORTE-01-0145-FEDER-000023, NORTE-01-0145-FEDER-000013, 2020.07946
Amsterdam Neuroscience	CIA-2019-03-A
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	320030_130237
European Social Fund	FI17/00294, PI19/01171
Else Kröner-Fresenius-Stiftung	2017_A101
ZonMw	016.156.318, 165.610.002, 916.86.038, 917.15.318
National Institute of Mental Health	R01MH121520, R01MH104648, R01MH116147, K24MH121571, R01MH117601, R21MH093889, R01MH085900, R21MH101441, R01MH111794, R01AG059874, R33MH107589, P41EB015922, 5R01MH116038, R01MH081864, R01MH126981, R01MH123163, K23 MH115206, R01MH121246, R01MH126213
The Wellcome Trust DBT India Alliance	IA/CPHE/18/1/503956, 500236/Z/11/Z
National Institutes of Health	U54 EB020403

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10.1038/s41380-023-02077-0

Cite this

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., ... van Wingen, G. A. (2023). The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium. Molecular Psychiatry, 28(10), 4307-4319. https://doi.org/10.1038/s41380-023-02077-0

@article{5b5160b1d91a4afc93755834e1d13dec,

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

abstract = "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{\textquoteright}s d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen{\textquoteright}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.",

author = "Bruin, {Willem B.} and Yoshinari Abe and Pino Alonso and Alan Anticevic and Backhausen, {Lea L.} and Srinivas Balachander and Nuria Bargallo and Batistuzzo, {Marcelo C.} and Francesco Benedetti and {Bertolin Triquell}, Sara and Silvia Brem and Federico Calesella and Beatriz Couto and Denys, {Damiaan A.J.P.} and Echevarria, {Marco A.N.} and Eng, {Goi Khia} and S{\'o}nia Ferreira and Feusner, {Jamie D.} and Grazioplene, {Rachael G.} and Patricia Gruner and Guo, {Joyce Y.} and Kristen Hagen and Bjarne Hansen and Yoshiyuki Hirano and Hoexter, {Marcelo Q.} and Neda Jahanshad and Fern Jaspers-Fayer and Selina Kasprzak and Minah Kim and Kathrin Koch and {Bin Kwak}, Yoo and Kwon, {Jun Soo} and Luisa Lazaro and Li, {Chiang Shan R.} and Christine Lochner and Rachel Marsh and Ignacio Mart{\'i}nez-Zalaca{\'i}n and Menchon, {Jose M.} and Moreira, {Pedro S.} and Pedro Morgado and Akiko Nakagawa and Tomohiro Nakao and Narayanaswamy, {Janardhanan C.} and Nurmi, {Erika L.} and Zorrilla, {Jose C.Pariente} and John Piacentini and Maria Pic{\'o}-P{\'e}rez and Fabrizio Piras and Federica Piras and Christopher Pittenger and Reddy, {Janardhan Y.C.} and Daniela Rodriguez-Manrique and Yuki Sakai and Eiji Shimizu and Venkataram Shivakumar and Simpson, {Blair H.} and Carles Soriano-Mas and Nuno Sousa and Gianfranco Spalletta and Stern, {Emily R.} and {Evelyn Stewart}, S. and Szeszko, {Philip R.} and Jinsong Tang and Thomopoulos, {Sophia I.} and Thorsen, {Anders L.} and Tokiko Yoshida and Hirofumi Tomiyama and Benedetta Vai and Veer, {Ilya M.} and Ganesan Venkatasubramanian and Vetter, {Nora C.} and Chris Vriend and Susanne Walitza and Lea Waller and Zhen Wang and Anri Watanabe and Nicole Wolff and Yun, {Je Yeon} and Qing Zhao and {van Leeuwen}, {Wieke A.} and {van Marle}, {Hein J.F.} and {van de Mortel}, {Laurens A.} and {van der Straten}, Anouk and {van der Werf}, {Ysbrand D.} and Honami Arai and Irene Bollettini and Escalona, {Rosa Calvo} and Ana Coelho and Federica Colombo and Leila Darwich and Martine Fontaine and Toshikazu Ikuta and Ipser, {Jonathan C.} and Asier Juaneda-Segu{\'i} and Hitomi Kitagawa and Gerd Kvale and Mafalda Machado-Sousa and Astrid Morer and Takashi Nakamae and Jin Narumoto and Joseph O{\textquoteright}Neill and Sho Okawa and Eva Real and Veit Roessner and Sato, {Joao R.} and Cinto Segal{\`a}s and Shavitt, {Roseli G.} and Veltman, {Dick J.} and Kei Yamada and {van Leeuwen}, {Wieke A.} and {van Marle}, {Hein J.F.} and {van de Mortel}, {Laurens A.} and {van der Straten}, Anouk and {van der Werf}, {Ysbrand D.} and {van den Heuvel}, {Odile A.} and {van Wingen}, {Guido A.} and Thompson, {Paul M.} and Stein, {Dan J.} and {van den Heuvel}, {Odile A.} and {van Wingen}, {Guido A.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = oct,

doi = "10.1038/s41380-023-02077-0",

language = "אנגלית",

volume = "28",

pages = "4307--4319",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "10",

}

Bruin, WB, Abe, Y, Alonso, P, Anticevic, A, Backhausen, LL, Balachander, S, Bargallo, N, Batistuzzo, MC, Benedetti, F, Bertolin Triquell, S, Brem, S, Calesella, F, Couto, B, Denys, DAJP, Echevarria, MAN, Eng, GK, Ferreira, S, Feusner, JD, Grazioplene, RG, Gruner, P, Guo, JY, Hagen, K, Hansen, B, Hirano, Y, Hoexter, MQ, Jahanshad, N, Jaspers-Fayer, F, Kasprzak, S, Kim, M, Koch, K, Bin Kwak, Y, Kwon, JS, Lazaro, L, Li, CSR, Lochner, C, Marsh, R, Martínez-Zalacaín, I, Menchon, JM, Moreira, PS, Morgado, P, Nakagawa, A, Nakao, T, Narayanaswamy, JC, Nurmi, EL, Zorrilla, JCP, Piacentini, J, Picó-Pérez, M, Piras, F, Piras, F, Pittenger, C, Reddy, JYC, Rodriguez-Manrique, D, Sakai, Y, Shimizu, E, Shivakumar, V, Simpson, BH, Soriano-Mas, C, Sousa, N, Spalletta, G, Stern, ER, Evelyn Stewart, S, Szeszko, PR, Tang, J, Thomopoulos, SI, Thorsen, AL, Yoshida, T, Tomiyama, H, Vai, B, Veer, IM, Venkatasubramanian, G, Vetter, NC, Vriend, C, Walitza, S, Waller, L, Wang, Z, Watanabe, A, Wolff, N, Yun, JY, Zhao, Q, van Leeuwen, WA, van Marle, HJF, van de Mortel, LA, van der Straten, A, van der Werf, YD, Arai, H, Bollettini, I, Escalona, RC, Coelho, A, Colombo, F, Darwich, L, Fontaine, M, Ikuta, T, Ipser, JC, Juaneda-Seguí, A, Kitagawa, H, Kvale, G, Machado-Sousa, M, Morer, A, Nakamae, T, Narumoto, J, O’Neill, J, Okawa, S, Real, E, Roessner, V, Sato, JR, Segalàs, C, Shavitt, RG, Veltman, DJ, Yamada, K, van Leeuwen, WA, van Marle, HJF, van de Mortel, LA, van der Straten, A, van der Werf, YD, van den Heuvel, OA, van Wingen, GA, Thompson, PM, Stein, DJ, van den Heuvel, OA & van Wingen, GA 2023, 'The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium', Molecular Psychiatry, vol. 28, no. 10, pp. 4307-4319. https://doi.org/10.1038/s41380-023-02077-0

TY - JOUR

T1 - The functional connectome in obsessive-compulsive disorder

T2 - resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium

AU - Bruin, Willem B.

AU - Abe, Yoshinari

AU - Alonso, Pino

AU - Anticevic, Alan

AU - Backhausen, Lea L.

AU - Balachander, Srinivas

AU - Bargallo, Nuria

AU - Batistuzzo, Marcelo C.

AU - Benedetti, Francesco

AU - Bertolin Triquell, Sara

AU - Brem, Silvia

AU - Calesella, Federico

AU - Couto, Beatriz

AU - Denys, Damiaan A.J.P.

AU - Echevarria, Marco A.N.

AU - Eng, Goi Khia

AU - Ferreira, Sónia

AU - Feusner, Jamie D.

AU - Grazioplene, Rachael G.

AU - Gruner, Patricia

AU - Guo, Joyce Y.

AU - Hagen, Kristen

AU - Hansen, Bjarne

AU - Hirano, Yoshiyuki

AU - Hoexter, Marcelo Q.

AU - Jahanshad, Neda

AU - Jaspers-Fayer, Fern

AU - Kasprzak, Selina

AU - Kim, Minah

AU - Koch, Kathrin

AU - Bin Kwak, Yoo

AU - Kwon, Jun Soo

AU - Lazaro, Luisa

AU - Li, Chiang Shan R.

AU - Lochner, Christine

AU - Marsh, Rachel

AU - Martínez-Zalacaín, Ignacio

AU - Menchon, Jose M.

AU - Moreira, Pedro S.

AU - Morgado, Pedro

AU - Nakagawa, Akiko

AU - Nakao, Tomohiro

AU - Narayanaswamy, Janardhanan C.

AU - Nurmi, Erika L.

AU - Zorrilla, Jose C.Pariente

AU - Piacentini, John

AU - Picó-Pérez, Maria

AU - Piras, Fabrizio

AU - Piras, Federica

AU - Pittenger, Christopher

AU - Reddy, Janardhan Y.C.

AU - Rodriguez-Manrique, Daniela

AU - Sakai, Yuki

AU - Shimizu, Eiji

AU - Shivakumar, Venkataram

AU - Simpson, Blair H.

AU - Soriano-Mas, Carles

AU - Sousa, Nuno

AU - Spalletta, Gianfranco

AU - Stern, Emily R.

AU - Evelyn Stewart, S.

AU - Szeszko, Philip R.

AU - Tang, Jinsong

AU - Thomopoulos, Sophia I.

AU - Thorsen, Anders L.

AU - Yoshida, Tokiko

AU - Tomiyama, Hirofumi

AU - Vai, Benedetta

AU - Veer, Ilya M.

AU - Venkatasubramanian, Ganesan

AU - Vetter, Nora C.

AU - Vriend, Chris

AU - Walitza, Susanne

AU - Waller, Lea

AU - Wang, Zhen

AU - Watanabe, Anri

AU - Wolff, Nicole

AU - Yun, Je Yeon

AU - Zhao, Qing

AU - van Leeuwen, Wieke A.

AU - van Marle, Hein J.F.

AU - van de Mortel, Laurens A.

AU - van der Straten, Anouk

AU - van der Werf, Ysbrand D.

AU - Arai, Honami

AU - Bollettini, Irene

AU - Escalona, Rosa Calvo

AU - Coelho, Ana

AU - Colombo, Federica

AU - Darwich, Leila

AU - Fontaine, Martine

AU - Ikuta, Toshikazu

AU - Ipser, Jonathan C.

AU - Juaneda-Seguí, Asier

AU - Kitagawa, Hitomi

AU - Kvale, Gerd

AU - Machado-Sousa, Mafalda

AU - Morer, Astrid

AU - Nakamae, Takashi

AU - Narumoto, Jin

AU - O’Neill, Joseph

AU - Okawa, Sho

AU - Real, Eva

AU - Roessner, Veit

AU - Sato, Joao R.

AU - Segalàs, Cinto

AU - Shavitt, Roseli G.

AU - Veltman, Dick J.

AU - Yamada, Kei

AU - van Leeuwen, Wieke A.

AU - van Marle, Hein J.F.

AU - van de Mortel, Laurens A.

AU - van der Straten, Anouk

AU - van der Werf, Ysbrand D.

AU - van den Heuvel, Odile A.

AU - van Wingen, Guido A.

AU - Thompson, Paul M.

AU - Stein, Dan J.

AU - van den Heuvel, Odile A.

AU - van Wingen, Guido A.

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85156271143&partnerID=8YFLogxK

U2 - 10.1038/s41380-023-02077-0

DO - 10.1038/s41380-023-02077-0

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 37131072

AN - SCOPUS:85156271143

SN - 1359-4184

VL - 28

SP - 4307

EP - 4319

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 10

ER -

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

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