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

Abstract Background 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). Methods 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. Results 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. Conclusions 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.

[1]  I. Melle,et al.  Mapping the Heterogeneous Phenotype of Schizophrenia and Bipolar Disorder Using Normative Models , 2018, JAMA psychiatry.

[2]  Christian Sorg,et al.  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 , 2018, Neuroscience & Biobehavioral Reviews.

[3]  A. Greenshaw,et al.  Decreased Left Putamen and Thalamus Volume Correlates with Delusions in First-Episode Schizophrenia Patients , 2017, Front. Psychiatry.

[4]  Jessica Bradshaw,et al.  Anxiety Disorders and Obsessive-Compulsive Disorder in Individuals with Autism Spectrum Disorder , 2017, Current Psychiatry Reports.

[5]  Mattia Veronese,et al.  A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia , 2017, JAMA psychiatry.

[6]  Hye-Geum Kim,et al.  Repetitive transcranial magnetic stimulation of the supplementary motor area in treatment-resistant obsessive-compulsive disorder: An open–label pilot study , 2017, Journal of Clinical Neuroscience.

[7]  Katya Rubia,et al.  Comparative Multimodal Meta-analysis of Structural and Functional Brain Abnormalities in Autism Spectrum Disorder and Obsessive-Compulsive Disorder , 2017, Biological Psychiatry.

[8]  J. Os,et al.  The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum , 2017, Psychological Medicine.

[9]  T. Robbins,et al.  A trans-diagnostic perspective on obsessive-compulsive disorder , 2017, Psychological Medicine.

[10]  P. Bebbington,et al.  Transdiagnostic Extension of Delusions: Schizophrenia and Beyond , 2017, Schizophrenia bulletin.

[11]  A. MacDonald Studying Delusions Within Research Domain Criteria: The Challenge of Configural Traits When Building a Mechanistic Foundation for Abnormal Beliefs. , 2017, Schizophrenia bulletin.

[12]  J. Kable,et al.  Common Dimensional Reward Deficits Across Mood and Psychotic Disorders: A Connectome-Wide Association Study. , 2017, The American journal of psychiatry.

[13]  Murat Yücel,et al.  Altered functional network architecture in orbitofronto‐striato‐thalamic circuit of unmedicated patients with obsessive‐compulsive disorder , 2017, Human brain mapping.

[14]  S. Chabardès,et al.  Modulation of motor inhibition by subthalamic stimulation in obsessive-compulsive disorder , 2016, Translational psychiatry.

[15]  E. Scotti-Muzzi,et al.  Schizo-obsessive spectrum disorders: an update , 2016, CNS Spectrums.

[16]  Hans Knutsson,et al.  Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates , 2016, Proceedings of the National Academy of Sciences.

[17]  Chunshui Yu,et al.  Distinct disruptions of resting-state functional brain networks in familial and sporadic schizophrenia , 2016, Scientific Reports.

[18]  Lauren E. Ethridge,et al.  Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers. , 2016, The American journal of psychiatry.

[19]  Tae Young Lee,et al.  Altered Fronto-Temporal Functional Connectivity in Individuals at Ultra-High-Risk of Developing Psychosis , 2015, PloS one.

[20]  P. J. McKenna,et al.  Failure of deactivation in the default mode network: a trait marker for schizophrenia? , 2014, Psychological Medicine.

[21]  Christian Kaufmann,et al.  Default mode network subsystem alterations in obsessive–compulsive disorder , 2014, British Journal of Psychiatry.

[22]  Katie L. McMahon,et al.  A multivariate distance-based analytic framework for connectome-wide association studies , 2014, NeuroImage.

[23]  Gereon R. Fink,et al.  Dorsal and Ventral Attention Systems , 2014, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[24]  Bruce N Cuthbert,et al.  The RDoC framework: facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology , 2014, World psychiatry : official journal of the World Psychiatric Association.

[25]  Amanda V. Utevsky,et al.  Precuneus Is a Functional Core of the Default-Mode Network , 2014, The Journal of Neuroscience.

[26]  Jian Wang,et al.  Morphologic and Functional Connectivity Alterations of Corticostriatal and Default Mode Network in Treatment-Naïve Patients with Obsessive-Compulsive Disorder , 2013, PloS one.

[27]  Theodore P. Zanto,et al.  Fronto-parietal network: flexible hub of cognitive control , 2013, Trends in Cognitive Sciences.

[28]  Stephan Heckers,et al.  Definition and description of schizophrenia in the DSM-5 , 2013, Schizophrenia Research.

[29]  J. Frazier,et al.  "Autism-plus" spectrum disorders: intersection with psychosis and the schizophrenia spectrum. , 2013, Child and adolescent psychiatric clinics of North America.

[30]  P. Michalopoulou,et al.  Differential diagnosis of obsessive-compulsive symptoms from delusions in schizophrenia: A phenomenological approach. , 2013, World journal of psychiatry.

[31]  Marc Joliot,et al.  Links among resting-state default-mode network, salience network, and symptomatology in schizophrenia , 2013, Schizophrenia Research.

[32]  R. Kahn,et al.  Dopaminergic function in the psychosis spectrum: an [18F]-DOPA imaging study in healthy individuals with auditory hallucinations. , 2013, Schizophrenia bulletin.

[33]  Evan M. Gordon,et al.  Phenotypic Variability in Resting-State Functional Connectivity: Current Status , 2013, Brain Connect..

[34]  R. Murray,et al.  Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. , 2012, The American journal of psychiatry.

[35]  Y. D. van der Werf,et al.  Presupplementary motor area hyperactivity during response inhibition: a candidate endophenotype of obsessive-compulsive disorder. , 2012, The American journal of psychiatry.

[36]  Jonathan D. Power,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[37]  S. Rauch,et al.  Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways , 2012, Trends in Cognitive Sciences.

[38]  Taylor W. Schmitz,et al.  Exploring the Neural Correlates of Delusions of Reference , 2011, Biological Psychiatry.

[39]  Dan J Stein,et al.  Should an obsessive–compulsive spectrum grouping of disorders be included in DSM‐V? , 2010, Depression and anxiety.

[40]  B. Harrison,et al.  Altered Cortico-Striatal Functional Connectivity in Obsessive-Compulsive Disorder , 2009, NeuroImage.

[41]  Tyrone D. Cannon,et al.  Obsessive compulsive symptoms in the psychosis prodrome: Correlates of clinical and functional outcome , 2009, Schizophrenia Research.

[42]  J. Kwon,et al.  Neuroimaging in obsessive–compulsive disorder , 2009, Expert review of neurotherapeutics.

[43]  Jean-Loup Guillaume,et al.  Fast unfolding of communities in large networks , 2008, 0803.0476.

[44]  S. Woolf The meaning of translational research and why it matters. , 2008, JAMA.

[45]  L. Sass Self and World in Schizophrenia: Three Classic Approaches , 2002 .

[46]  D. Linszen,et al.  Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders. , 1999, The Journal of clinical psychiatry.

[47]  S. Everling,et al.  The antisaccade: a review of basic research and clinical studies , 1998, Neuropsychologia.

[48]  W. Goodman,et al.  The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. , 1989, Archives of general psychiatry.

[49]  R. Chan,et al.  Altered Functional Connectivity of the Default Mode Network in Patients With Schizo-obsessive Comorbidity: A Comparison Between Schizophrenia and Obsessive-compulsive Disorder , 2019, Schizophrenia bulletin.

[50]  A. Malhotra,et al.  Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. , 2015, JAMA psychiatry.

[51]  G. Fink,et al.  Dorsal and Ventral Attention Systems: Distinct Neural Circuits but Collaborative Roles , 2013 .

[52]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity , 2011 .

[53]  B. Kirkpatrick,et al.  The heterogeneity of the long-term course of schizophrenia. , 1988, Schizophrenia bulletin.

[54]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[55]  C. Beckmann,et al.  Frontiers in Systems Neuroscience Systems Neuroscience Review Article , 2022 .