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. 2023 Oct;28(10):4307-4319.
doi: 10.1038/s41380-023-02077-0. Epub 2023 May 2.

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

Willem B Bruin  1   2 , Yoshinari Abe  3 , Pino Alonso  4   5   6   7 , Alan Anticevic  8 , Lea L Backhausen  9 , Srinivas Balachander  10 , Nuria Bargallo  7   11   12 , Marcelo C Batistuzzo  13   14 , Francesco Benedetti  15   16 , Sara Bertolin Triquell  17 , Silvia Brem  18   19 , Federico Calesella  15   16 , Beatriz Couto  20   21   22 , Damiaan A J P Denys  23   24 , Marco A N Echevarria  13 , Goi Khia Eng  25   26 , Sónia Ferreira  20   21   22 , Jamie D Feusner  27   28   29 , Rachael G Grazioplene  8 , Patricia Gruner  8 , Joyce Y Guo  30 , Kristen Hagen  31   32   33 , Bjarne Hansen  32   34 , Yoshiyuki Hirano  35 , Marcelo Q Hoexter  13 , Neda Jahanshad  36 , Fern Jaspers-Fayer  37 , Selina Kasprzak  38   39 , Minah Kim  40   41 , Kathrin Koch  42 , Yoo Bin Kwak  43 , Jun Soo Kwon  40   41   43 , Luisa Lazaro  7   12   44   45 , Chiang-Shan R Li  8 , Christine Lochner  46 , Rachel Marsh  47 , Ignacio Martínez-Zalacaín  17   48 , Jose M Menchon  7   17   48 , Pedro S Moreira  20   21   49 , Pedro Morgado  20   21   22 , Akiko Nakagawa  35 , Tomohiro Nakao  50 , Janardhanan C Narayanaswamy  51   52 , Erika L Nurmi  53 , Jose C Pariente Zorrilla  12 , John Piacentini  54 , Maria Picó-Pérez  20   21   55 , Fabrizio Piras  56 , Federica Piras  56 , Christopher Pittenger  8 , Janardhan Y C Reddy  10 , Daniela Rodriguez-Manrique  57   58   59 , Yuki Sakai  3   60 , Eiji Shimizu  35   61   62 , Venkataram Shivakumar  63 , Blair H Simpson  19   47 , Carles Soriano-Mas  7   17   64 , Nuno Sousa  21   22 , Gianfranco Spalletta  56   65 , Emily R Stern  25   26 , S Evelyn Stewart  37   66   67 , Philip R Szeszko  68   69 , Jinsong Tang  70 , Sophia I Thomopoulos  36 , Anders L Thorsen  32   34 , Tokiko Yoshida  35 , Hirofumi Tomiyama  50 , Benedetta Vai  16 , Ilya M Veer  71 , Ganesan Venkatasubramanian  10 , Nora C Vetter  9   72 , Chris Vriend  38   39   73   74 , Susanne Walitza  18 , Lea Waller  75 , Zhen Wang  76 , Anri Watanabe  3 , Nicole Wolff  9 , Je-Yeon Yun  41   77 , Qing Zhao  76 , Wieke A van Leeuwen  23   24 , Hein J F van Marle  38   78 , Laurens A van de Mortel  23   24 , Anouk van der Straten  23   24 , Ysbrand D van der Werf  39   73   74 ; ENIGMA-OCD Working Group; Paul M Thompson  36 , Dan J Stein  79 , Odile A van den Heuvel  38   39   73 , Guido A van Wingen  80   81
Collaborators, Affiliations

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

Willem B Bruin et al. Mol Psychiatry. 2023 Oct.

Erratum in

  • Correction: The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.
    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 CR, 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; ENIGMA-OCD Working Group; Thompson PM, Stein DJ, van den Heuvel OA, van Wingen GA. Bruin WB, et al. Mol Psychiatry. 2023 Oct;28(10):4320. doi: 10.1038/s41380-023-02211-y. Mol Psychiatry. 2023. PMID: 37582859 Free PMC article. No abstract available.

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.

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Conflict of interest statement

AA consults and holds equity with Neumora Therapeutics (formerly BlackThorn Therapeutics) and Manifest Technologies. AA also serves on the technology advisory board of Neumora Therapeutics and on the board of directors for Manifest Technologies. AA is a co-inventor on the following patents: AA, Murray JD, Ji JL: Systems and Methods for Neuro-Behavioral Relationships in Dimensional Geometric Embedding (N-BRIDGE), PCT International Application No. PCT/US2119/022110, filed March 13, 2019 and Murray JD, AA, Martin, WJ: Methods and tools for detecting, diagnosing, predicting, prognosticating, or treating a neurobehavioral phenotype in a subject, U.S. Application No.16/149, filed on October 2, 2018, U.S. Application for PCT International Application No.18/054, 009 filed on October 2, 2018. JDF received consultant fees from NOCD, Inc. PM has received in the past 3 years grants, CME-related honoraria, or consulting fees from Angelini, AstraZeneca, Bial Foundation, Biogen, DGS-Portugal, FCT, FLAD, Janssen-Cilag, Gulbenkian Foundation, Lundbeck, Springer Healthcare, Tecnimede and 2CA-Braga. ELN disclosed that she is an unpaid advisory board member of Tourette Association of America and Myriad Genetics. In the last three years, BHS has received royalties from UpToDate, Inc, and Cambridge University Press and a stipend from the American Medical Association for serving as Associate Editor of JAMA-Psychiatry. PMT received unrelated research grant support from Biogen, Inc. All other individually-named authors in- and outside of the ENIGMA-OCD working group reported no biomedical financial interests or potential conflicts of interest.

Figures

Fig. 1
Fig. 1. Functional parcellation atlas used to extract time series.
Parcels depict the 400 regions-of-interest (ROI) matched to 17 large scale resting-state networks from Schaefer and colleagues [35].
Fig. 2
Fig. 2. Effect sizes (Cohen’s d) for group differences in ROI-to-ROI functional connectivity between OCD patients and HC from pooled samples across age groups.
Provided labels in this figure are for assigned networks only (individual ROI labels and ROI to network mapping can be found in Supplement). TempPar Temporal Parietal, Cont Frontoparietal Control, SalVentAttn Salience/Ventral Attention, DorsAttn Dorsal Attention, SomMot Sensorimotor, VisCent Visual Central (Visual A), VisPeri Visual Peripheral (Visual B).
Fig. 3
Fig. 3. Effect sizes (Cohen’s d) for group differences in measures of local activity between OCD patients and HC.
(A) ReHo, (B) regional fALFF. Provided coordinates are in MNI space. L = Left Hemisphere, R = Right Hemisphere.
Fig. 4
Fig. 4. Effect sizes (Cohen’s d) for group differences in ROI-to-ROI functional connectivity between medicated OCD patients and HC.
Provided labels in this figure are for assigned networks only (individual ROI labels and ROI to network mapping can be found in Supplement). TempPar Temporal Parietal, Cont Frontoparietal Control, SalVentAttn Salience/Ventral Attention, DorsAttn Dorsal Attention, SomMot Sensorimotor, VisCent Visual Central (Visual A), VisPeri Visual Peripheral (Visual B).
Fig. 5
Fig. 5. Effect sizes (Cohen’s d) for group differences in ROI-to-ROI functional connectivity between high severity OCD patients and HC.
Provided labels in this figure are for assigned networks only (individual ROI labels can be found in Supplement). TempPar Temporal Parietal, Cont Frontoparietal Control, SalVentAttn Salience/Ventral Attention, DorsAttn Dorsal Attention, SomMot Sensorimotor, VisCent Visual Central (Visual A), VisPeri Visual Peripheral (Visual B).
Fig. 6
Fig. 6. Performance for obsessive-compulsive disorder classification using different resting-state fMRI derived features. Boxplots summarize classification metrics obtained across cross-validation iterations.
Dashed lines represent chance-level performance. ROC-AUC area under the received operator curve, ROI region of interest, FC functional connectivity, fALFF fractional amplitude of lower frequency fluctuations, ReHo regional homogeneity.
See this image and copyright information in PMC

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