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Distinct neural networks associated with obsession and delusion: a connectome-wide association study

Published online by Cambridge University Press:  30 January 2020

Tae Young Lee
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
Wi Hoon Jung
Department of Psychology, Daegu University, Gyeongsan, Republic of Korea
Yoo Bin Kwak
Department of Brain and Cognitive Science, Seoul National University College of Natural Science, Seoul, Republic of Korea
Youngwoo B. Yoon
Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA
Junhee Lee
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
Minah Kim
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
Euitae Kim
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
Jun Soo Kwon
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea Department of Brain and Cognitive Science, Seoul National University College of Natural Science, Seoul, Republic of Korea
E-mail address:



Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS).


Our study sample comprised of 96 patients with obsessive–compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression.


Obsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associated with the precuneus. Follow-up seed-based RSFC and modularity analyses revealed that obsession was related to aberrant inter-network connectivity strength. Additional inter-network analyses demonstrated the association between obsession severity and inter-network connectivity between the frontoparietal control network and the dorsal attention network.


Our CWAS study based on the Research Domain Criteria (RDoC) provides novel evidence for the circuit-level functional dysconnectivity associated with obsession and delusion severity across diagnostic boundaries. Further refinement and accumulation of biomarkers from studies embedded within the RDoC framework would provide useful information in treating individuals who have some obsession or delusion symptoms but cannot be identified by the category of clinical symptoms alone.

Original Articles
Copyright © Cambridge University Press 2020

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Both authors contributed equally to this work.


Bebbington, P., & Freeman, D. (2017). Transdiagnostic extension of delusions: Schizophrenia and beyond. Schizophrenia Bulletin, 43, 273282.CrossRefGoogle ScholarPubMed
Beucke, J. C., Sepulcre, J., Eldaief, M. C., Sebold, M., Kathmann, N., & Kaufmann, C. (2014). Default mode network subsystem alterations in obsessive-compulsive disorder. British Journal of Psychiatry, 205, 376382.CrossRefGoogle ScholarPubMed
Blondel, V. D., Guillaume, J. L., Lambiotte, R., & Lefebvre, E. (2008). Fast unfolding of communities in large networks. Journal of Statistical Mechanics (online), 2008, P10008.CrossRefGoogle Scholar
Carlisi, C. O., Norman, L. J., Lukito, S. S., Radua, J., Mataix-Cols, D., & Rubia, K. (2017). Comparative multimodal meta-analysis of structural and functional brain abnormalities in autism spectrum disorder and obsessive-compulsive disorder. Biological Psychiatry, 82, 83102.CrossRefGoogle ScholarPubMed
Carpenter, W. T. Jr., & Kirkpatrick, B. (1988). The heterogeneity of the long-term course of schizophrenia. Schizophrenia Bulletin, 14, 645652.CrossRefGoogle ScholarPubMed
Clementz, B. A., Sweeney, J. A., Hamm, J. P., Ivleva, E. I., Ethridge, L. E., Pearlson, G. D., & Tamminga, C. A. (2016). Identification of distinct psychosis biotypes using brain-based biomarkers. American Journal of Psychiatry, 173, 373384.CrossRefGoogle ScholarPubMed
Cochran, D. M., Dvir, Y., & Frazier, J. A. (2013). ‘Autism-plus’ spectrum disorders: Intersection with psychosis and the schizophrenia spectrum. Child and Adolescent Psychiatric Clinics of North America, 22, 609627.CrossRefGoogle ScholarPubMed
Cole, D. M., Smith, S. M., & Beckmann, C. F. (2010). Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Frontiers in Systems Neuroscience, 4, 8.Google ScholarPubMed
Cuthbert, B. N. (2014). The RDoC framework: Facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology. World Psychiatry, 13, 2835.CrossRefGoogle ScholarPubMed
de Haan, L., Linszen, D. H., & Gorsira, R. (1999). Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders. Journal of Clinical Psychiatry, 60, 364365.CrossRefGoogle ScholarPubMed
de Wit, S. J., de Vries, F. E., van der Werf, Y. D., Cath, D. C., Heslenfeld, D. J., Veltman, E. M., & van den Heuvel, O. A. (2012). Presupplementary motor area hyperactivity during response inhibition: A candidate endophenotype of obsessive-compulsive disorder. American Journal of Psychiatry, 169, 11001108.CrossRefGoogle ScholarPubMed
Demjaha, A., Murray, R. M., McGuire, P. K., Kapur, S., & Howes, O. D. (2012). Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. American Journal of Psychiatry, 169, 12031210.CrossRefGoogle ScholarPubMed
Eklund, A., Nichols, T. E., & Knutsson, H. (2016). Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences of the United States of America, 113, 79007905.CrossRefGoogle ScholarPubMed
Everling, S., & Fischer, B. (1998). The antisaccade: A review of basic research and clinical studies. Neuropsychologia, 36, 885899.CrossRefGoogle ScholarPubMed
Gillan, C. M., Fineberg, N. A., & Robbins, T. W. (2017). A trans-diagnostic perspective on obsessive-compulsive disorder. Psychological Medicine, 47, 15281548.CrossRefGoogle ScholarPubMed
Goodman, W. K., Price, L. H., Rasmussen, S. A., Mazure, C., Fleischmann, R. L., Hill, C. L., & Charney, D. S. (1989). The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Archives of General Psychiatry, 46, 10061011.CrossRefGoogle ScholarPubMed
Guloksuz, S., & van Os, J. (2018). The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum. Psychological Medicine, 48, 229244.CrossRefGoogle ScholarPubMed
Gursel, D. A., Avram, M., Sorg, C., Brandl, F., & Koch, K. (2018). Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: A meta-analysis of resting-state functional connectivity. Neuroscience & Biobehavioral Reviews, 87, 151160.CrossRefGoogle ScholarPubMed
Harrison, B. J., Soriano-Mas, C., Pujol, J., Ortiz, H., Lopez-Sola, M., Hernandez-Ribas, R., & Cardoner, N. (2009). Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Archives of General Psychiatry, 66, 11891200.CrossRefGoogle ScholarPubMed
Hou, J., Song, L., Zhang, W., Wu, W., Wang, J., Zhou, D., … Li, H. (2013). Morphologic and functional connectivity alterations of corticostriatal and default mode network in treatment-naive patients with obsessive-compulsive disorder. PLoS ONE, 8, e83931.CrossRefGoogle ScholarPubMed
Howes, O. D., Shotbolt, P., Bloomfield, M., Daalman, K., Demjaha, A., Diederen, K. M., & Sommer, I. E. (2013). Dopaminergic function in the psychosis spectrum: An [18F]-DOPA imaging study in healthy individuals with auditory hallucinations. Schizophrenia Bulletin, 39, 807814.CrossRefGoogle Scholar
Huang, X., Pu, W., Li, X., Greenshaw, A. J., Dursun, S. M., Xue, Z., … Liu, Z. (2017). Decreased left Putamen and thalamus volume correlates with delusions in first-episode schizophrenia patients. Frontiers in Psychiatry, 8, 245.CrossRefGoogle ScholarPubMed
Jauhar, S., Nour, M. M., Veronese, M., Rogdaki, M., Bonoldi, I., Azis, M., … Howes, O. D. (2017). A test of the transdiagnostic dopamine hypothesis of psychosis using positron emission tomographic imaging in bipolar affective disorder and schizophrenia. JAMA Psychiatry, 74, 12061213.CrossRefGoogle Scholar
Jung, W. H., Yucel, M., Yun, J. Y., Yoon, Y. B., Cho, K. I., Parkes, L., & Kwon, J. S. (2017). Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder. Human Brain Mapping, 38, 109119.CrossRefGoogle ScholarPubMed
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13, 261276.CrossRefGoogle Scholar
Kibleur, A., Gras-Combe, G., Benis, D., Bastin, J., Bougerol, T., Chabardes, S., & David, O. (2016). Modulation of motor inhibition by subthalamic stimulation in obsessive-compulsive disorder. Translational Psychiatry, 6, e922.CrossRefGoogle ScholarPubMed
Kwon, J. S., Jang, J. H., Choi, J. S., & Kang, D. H. (2009). Neuroimaging in obsessive-compulsive disorder. Expert Review of Neurotherapeutics, 9, 255269.CrossRefGoogle ScholarPubMed
Landin-Romero, R., McKenna, P. J., Salgado-Pineda, P., Sarro, S., Aguirre, C., Sarri, C., & Pomarol-Clotet, E. (2015). Failure of deactivation in the default mode network: A trait marker for schizophrenia? Psychological Medicine, 45, 13151325.CrossRefGoogle Scholar
Lee, Y. J., Koo, B. H., Seo, W. S., Kim, H. G., Kim, J. Y., & Cheon, E. J. (2017). Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open-label pilot study. Journal of Clinical Neuroscience, 44, 264268.CrossRefGoogle Scholar
MacDonald, A. W., 3rd. (2017). Studying delusions within Research Domain Criteria: the challenge of configural traits when building a mechanistic foundation for abnormal beliefs. Schizophr Bull, 43, 260262.CrossRefGoogle ScholarPubMed
Menon, M., Schmitz, T. W., Anderson, A. K., Graff, A., Korostil, M., Mamo, D., & Kapur, S. (2011). Exploring the neural correlates of delusions of reference. Biological Psychiatry, 70, 11271133.CrossRefGoogle ScholarPubMed
Milad, M. R., & Rauch, S. L. (2012). Obsessive-compulsive disorder: Beyond segregated cortico-striatal pathways. Trends in Cognitive Sciences, 16, 4351.CrossRefGoogle ScholarPubMed
Niendam, T. A., Berzak, J., Cannon, T. D., & Bearden, C. E. (2009). Obsessive compulsive symptoms in the psychosis prodrome: Correlates of clinical and functional outcome. Schizophrenia Research, 108, 170175.CrossRefGoogle ScholarPubMed
Orliac, F., Naveau, M., Joliot, M., Delcroix, N., Razafimandimby, A., Brazo, P., & Delamillieure, P. (2013). Links among resting-state default-mode network, salience network, and symptomatology in schizophrenia. Schizophrenia Research, 148, 7480.CrossRefGoogle Scholar
Oulis, P., Konstantakopoulos, G., Lykouras, L., & Michalopoulou, P. G. (2013). Differential diagnosis of obsessive-compulsive symptoms from delusions in schizophrenia: A phenomenological approach. World Journal of Psychiatry, 3, 5056.CrossRefGoogle ScholarPubMed
Phillips, K. A., Stein, D. J., Rauch, S. L., Hollander, E., Fallon, B. A., Barsky, A., & Leckman, J. (2010). Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V? Depression and Anxiety, 27, 528555.CrossRefGoogle ScholarPubMed
Postorino, V., Kerns, C. M., Vivanti, G., Bradshaw, J., Siracusano, M., & Mazzone, L. (2017). Anxiety disorders and obsessive-compulsive disorder in individuals with autism spectrum disorder. Current Psychiatry Reports, 19, 92.CrossRefGoogle ScholarPubMed
Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage, 59, 21422154.CrossRefGoogle ScholarPubMed
Sarpal, D. K., Robinson, D. G., Lencz TArgyelan, M., Ikuta, T., Karlsgodt, K., Gallego, J. A., & Malhotra, A. K. (2015). Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. JAMA Psychiatry, 72, 513.CrossRefGoogle ScholarPubMed
Sass, L. A. (2001). Self and world in schizophrenia: Three classic approaches. Philosophy, Psychiatry, & Psychology, 8, 251270.CrossRefGoogle Scholar
Satterthwaite, T. D., Vandekar, S. N., Wolf, D. H., Bassett, D. S., Ruparel, K., Shehzad, Z., & Gur, R. E. (2015). Connectome-wide network analysis of youth with psychosis-spectrum symptoms. Molecular Psychiatry, 20, 15081515.CrossRefGoogle ScholarPubMed
Scotti-Muzzi, E., & Saide, O. L. (2017). Schizo-obsessive spectrum disorders: An update. CNS Spectrums, 22, 258272.CrossRefGoogle ScholarPubMed
Sharma, A., Wolf, D. H., Ciric, R., Kable, J. W., Moore, T. M., Vandekar, S. N., & Satterthwaite, T. D. (2017). Common dimensional reward deficits across mood and psychotic disorders: A connectome-wide association study. American Journal of Psychiatry, 174, 657666.CrossRefGoogle ScholarPubMed
Shehzad, Z., Kelly, C., Reiss, P. T., Cameron Craddock, R., Emerson, J. W., McMahon, K., & Milham, M. P. (2014). A multivariate distance-based analytic framework for connectome-wide association studies. Neuroimage, 93(Pt 1), 7494.CrossRefGoogle ScholarPubMed
Tandon, R., Gaebel, W., Barch, D. M., Bustillo, J., Gur, R. E., Heckers, S., & Carpenter, W. (2013). Definition and description of schizophrenia in the DSM-5. Schizophrenia Research, 150, 310.CrossRefGoogle ScholarPubMed
Utevsky, A. V., Smith, D. V., & Huettel, S. A. (2014). Precuneus is a functional core of the default-mode network. Journal of Neuroscience, 34, 932940.CrossRefGoogle ScholarPubMed
Vaidya, C. J., & Gordon, E. M. (2013). Phenotypic variability in resting-state functional connectivity: Current status. Brain Connectivity, 3, 99120.CrossRefGoogle ScholarPubMed
Vossel, S., Geng, J. J., & Fink, G. R. (2014). Dorsal and ventral attention systems: Distinct neural circuits but collaborative roles. Neuroscientist, 20, 150159.CrossRefGoogle ScholarPubMed
Wang, Y. M., Zou, L. Q., Xie, W. L., Yang, Z. Y., Zhu, X. Z., Cheung, E. F. C., & Chan, R. C. K. (2019). Altered functional connectivity of the default mode network in patients with schizo-obsessive comorbidity: A comparison between schizophrenia and obsessive-compulsive disorder. Schizophrenia Bulletin, 45, 199210.CrossRefGoogle ScholarPubMed
Wolfers, T., Doan, N. T., Kaufmann, T., Alnaes, D., Moberget, T., Agartz, I., & Marquand, A. F. (2018). Mapping the heterogeneous phenotype of schizophrenia and bipolar disorder using normative models. JAMA Psychiatry, 75, 11461155.CrossRefGoogle ScholarPubMed
Woolf, S. H. (2008). The meaning of translational research and why it matters. JAMA, 299, 211213.CrossRefGoogle ScholarPubMed
Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., & Buckner, R. L. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106, 11251165.Google ScholarPubMed
Yoon, Y. B., Yun, J. Y., Jung, W. H., Cho, K. I., Kim, S. N., Lee, T. Y., & Kwon, J. S. (2015). Altered fronto-temporal functional connectivity in individuals at ultra-high-risk of developing psychosis. PLoS ONE, 10, e0135347.CrossRefGoogle ScholarPubMed
Zanto, T. P., & Gazzaley, A. (2013). Fronto-parietal network: Flexible hub of cognitive control. Trends in Cognitive Sciences, 17, 602603.CrossRefGoogle ScholarPubMed
Zhu, J., Zhuo, C., Liu, F., Qin, W., Xu, L., & Yu, C. (2016). Distinct disruptions of resting-state functional brain networks in familial and sporadic schizophrenia. Scientific Reports, 6, 23577.CrossRefGoogle ScholarPubMed

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Distinct neural networks associated with obsession and delusion: a connectome-wide association study
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