Transdiagnostic commonalities and differences in resting state functional connectivity of the default mode network in schizophrenia and major depression

Schizophrenia and depression are prevalent psychiatric disorders, but their underlying neural bases remains poorly understood. Neuroimaging evidence has pointed towards the relevance of functional connectivity aberrations in default mode network (DMN) hubs, dorso-medial prefrontal cortex and precuneus, in both disorders, but commonalities and differences in resting state functional connectivity of those two regions across disorders has not been formally assessed. Here, we took a transdiagnostic approach to investigate resting state functional connectivity of those two regions in 75 patients with schizophrenia and 82 controls from 4 scanning sites and 102 patients with depression and 106 controls from 3 sites. Our results demonstrate common dysconnectivity patterns as indexed by a significant reduction of functional connectivity between precuneus and bilateral superior parietal lobe in schizophrenia and depression. Furthermore, our findings highlight diagnosis-specific connectivity reductions of the parietal operculum in schizophrenia relative to depression. In light of evidence that points towards the importance of the DMN for social cognitive abilities and well documented impairments of social interaction in both patient groups, it is conceivable that the observed transdiagnostic connectivity alterations may contribute to interpersonal difficulties, but this could not be assessed directly in our study as measures of social behavior were not available. Given the operculum's role in somatosensory integration, diagnosis-specific connectivity reductions may indicate a pathophysiological mechanism for basic self-disturbances that is characteristic of schizophrenia, but not depression.

[1]  Hang Joon Jo,et al.  Trouble at Rest: How Correlation Patterns and Group Differences Become Distorted After Global Signal Regression , 2012, Brain Connect..

[2]  Carrie L. Masten,et al.  Empathy for the social suffering of friends and strangers recruits distinct patterns of brain activation. , 2013, Social cognitive and affective neuroscience.

[3]  T. A. Kelley,et al.  Cortical mechanisms for shifting and holding visuospatial attention. , 2008, Cerebral cortex.

[4]  A. Lozano,et al.  Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression , 2008, Biological Psychiatry.

[5]  U. Habel,et al.  Neural correlates of depressive realism--an fMRI study on causal attribution in depression. , 2012, Journal of affective disorders.

[6]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[7]  Karl J. Friston,et al.  Dysconnection in Schizophrenia: From Abnormal Synaptic Plasticity to Failures of Self-monitoring , 2009, Schizophrenia bulletin.

[8]  J. P. Mccullough,et al.  Treatment for chronic depression using Cognitive Behavioral Analysis System of Psychotherapy (CBASP). , 2003, Journal of clinical psychology.

[9]  L. Parsons,et al.  Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. , 1999, The American journal of psychiatry.

[10]  Jong H. Yoon,et al.  General and Specific Functional Connectivity Disturbances in First-Episode Schizophrenia During Cognitive Control Performance , 2011, Biological Psychiatry.

[11]  Elizabeth A. Osuch,et al.  Retrosplenial cortex connectivity in schizophrenia , 2009, Psychiatry Research: Neuroimaging.

[12]  V. Calhoun,et al.  Differences in Resting-State Functional Magnetic Resonance Imaging Functional Network Connectivity Between Schizophrenia and Psychotic Bipolar Probands and Their Unaffected First-Degree Relatives , 2012, Biological Psychiatry.

[13]  L. Phillips,et al.  Rumination, depressive symptoms and awareness of illness in schizophrenia. , 2014, Behavioural and cognitive psychotherapy.

[14]  Thomas Fuchs,et al.  The Temporal Structure of Intentionality and Its Disturbance in Schizophrenia , 2007, Psychopathology.

[15]  L. DeLisi,et al.  The relationship between default mode network connectivity and social functioning in individuals at familial high-risk for schizophrenia , 2014, Schizophrenia Research.

[16]  V. Calhoun,et al.  Mentalizing in male schizophrenia patients is compromised by virtue of dysfunctional connectivity between task-positive and task-negative networks , 2012, Schizophrenia Research.

[17]  Daniel A. Schneider,et al.  Empathic behavioral and physiological responses to dynamic stimuli in depression , 2012, Psychiatry Research.

[18]  Bruce Luber,et al.  Self-specific processing in the default network: a single-pulse TMS study , 2010, Experimental Brain Research.

[19]  M. Tsakiris My body in the brain: A neurocognitive model of body-ownership , 2010, Neuropsychologia.

[20]  K. Vogeley,et al.  Resting-state functional network correlates of psychotic symptoms in schizophrenia , 2010, Schizophrenia Research.

[21]  Jonathan D. Power,et al.  Recent progress and outstanding issues in motion correction in resting state fMRI , 2015, NeuroImage.

[22]  Laura M. Tully,et al.  Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia. , 2014, Journal of abnormal psychology.

[23]  Yong He,et al.  Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia , 2014, Schizophrenia Research.

[24]  Karl J. Friston,et al.  Dysconnectivity Within the Default Mode in First-Episode Schizophrenia: A Stochastic Dynamic Causal Modeling Study With Functional Magnetic Resonance Imaging , 2014, Schizophrenia bulletin.

[25]  J. P. Hamilton,et al.  Neural systems approaches to understanding major depressive disorder: An intrinsic functional organization perspective , 2013, Neurobiology of Disease.

[26]  Simon B. Eickhoff,et al.  An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data , 2013, NeuroImage.

[27]  F. Aboitiz,et al.  Social Cognition in Schizophrenia: From Social Stimuli Processing to Social Engagement , 2013, Front. Psychiatry.

[28]  Leanne M. Williams,et al.  Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: a whole-brain diffusion tensor imaging tractography study , 2012, Neuroreport.

[29]  Mert R. Sabuncu,et al.  The influence of head motion on intrinsic functional connectivity MRI , 2012, NeuroImage.

[30]  Geoffrey Bird,et al.  Selective disruption of sociocognitive structural brain networks in autism and alexithymia. , 2014, Cerebral cortex.

[31]  Alan C. Evans,et al.  Brain Connectivity , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[32]  P. F. Liddle,et al.  Biological vulnerability to depression: linked structural and functional brain network findings , 2014, British Journal of Psychiatry.

[33]  A. Meyer-Lindenberg,et al.  The neurobiology of social environmental risk for schizophrenia: an evolving research field , 2014, Social Psychiatry and Psychiatric Epidemiology.

[34]  Deanna M. Barch,et al.  Conflict and error processing in an extended cingulo-opercular and cerebellar network in schizophrenia☆ , 2013, NeuroImage: Clinical.

[35]  Sarah E. Morris,et al.  Research Domain Criteria: cognitive systems, neural circuits, and dimensions of behavior , 2012, Dialogues in clinical neuroscience.

[36]  M. Bell,et al.  Social cognitive deficits in schizophrenia and their relationship to clinical and functional status , 2013, Psychiatry Research.

[37]  Nicolai Ladegaard,et al.  Higher-order social cognition in first-episode major depression , 2014, Psychiatry Research.

[38]  T. Insel,et al.  Toward the future of psychiatric diagnosis: the seven pillars of RDoC , 2013, BMC Medicine.

[39]  O. Blanke,et al.  Multisensory Mechanisms in Temporo-Parietal Cortex Support Self-Location and First-Person Perspective , 2011, Neuron.

[40]  A. Meyer-Lindenberg,et al.  Psychopathology and the Human Connectome: Toward a Transdiagnostic Model of Risk For Mental Illness , 2012, Neuron.

[41]  D. Sharp,et al.  Fractionating the Default Mode Network: Distinct Contributions of the Ventral and Dorsal Posterior Cingulate Cortex to Cognitive Control , 2011, The Journal of Neuroscience.

[42]  S. Petersen,et al.  A dual-networks architecture of top-down control , 2008, Trends in Cognitive Sciences.

[43]  Guido Nolte,et al.  Increased Resting-State Gamma-Band Connectivity in First-Episode Schizophrenia. , 2015, Schizophrenia bulletin.

[44]  E. Koster,et al.  The Default Mode Network and Recurrent Depression: A Neurobiological Model of Cognitive Risk Factors , 2012, Neuropsychology Review.

[45]  Conor Liston,et al.  Default Mode Network Mechanisms of Transcranial Magnetic Stimulation in Depression , 2014, Biological Psychiatry.

[46]  L. Yao,et al.  Resting-state abnormal baseline brain activity in unipolar and bipolar depression , 2012, Neuroscience Letters.

[47]  Simon B. Eickhoff,et al.  Meta-Analytically Informed Network Analysis of Resting State fMRI Reveals Hyperconnectivity in an Introspective Socio-Affective Network in Depression , 2014, PloS one.

[48]  S. Whitfield-Gabrieli,et al.  Impaired functional connectivity of brain reward circuitry in patients with schizophrenia and cannabis use disorder: Effects of cannabis and THC , 2014, Schizophrenia Research.

[49]  C. Frith,et al.  Exploring ‘theory of mind’ in people with schizophrenia , 1996, Psychological Medicine.

[50]  A. Gatherer,et al.  Sarcoma of the Larynx , 1958, The Journal of Laryngology & Otology.

[51]  V. Calhoun,et al.  Brain connectivity networks in schizophrenia underlying resting state functional magnetic resonance imaging. , 2012, Current topics in medicinal chemistry.

[52]  R. Jardri,et al.  Resting-state functional connectivity of the nucleus accumbens in auditory and visual hallucinations in schizophrenia. , 2015, Schizophrenia bulletin.

[53]  C. Frith Social cognition , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[54]  J. Zubieta,et al.  Accumbens functional connectivity during reward mediates sensation-seeking and alcohol use in high-risk youth. , 2013, Drug and alcohol dependence.

[55]  Rongjun Yu,et al.  Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self , 2014, Human brain mapping.

[56]  D. Delis,et al.  Dimensions of executive functioning in schizophrenia and their relationship with processing speed. , 2012, Schizophrenia bulletin.

[57]  Nadim Joni Shah,et al.  Minds Made for Sharing: Initiating Joint Attention Recruits Reward-related Neurocircuitry , 2010, Journal of Cognitive Neuroscience.

[58]  G. Fink,et al.  Eyes on me: an fMRI study of the effects of social gaze on action control. , 2011, Social cognitive and affective neuroscience.

[59]  Sun I. Kim,et al.  Aberrant neural responses to social rejection in patients with schizophrenia , 2014, Social neuroscience.

[60]  Arne D. Ekstrom,et al.  Multiple interacting brain areas underlie successful spatiotemporal memory retrieval in humans , 2014, Scientific Reports.

[61]  C. Frith,et al.  Schizophrenia and theory of mind , 2004, Psychological Medicine.

[62]  Benjamin J. Shannon,et al.  Functional-Anatomic Correlates of Memory Retrieval That Suggest Nontraditional Processing Roles for Multiple Distinct Regions within Posterior Parietal Cortex , 2004, The Journal of Neuroscience.

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

[64]  Hang Joon Jo,et al.  The perils of global signal regression for group comparisons: a case study of Autism Spectrum Disorders , 2013, Front. Hum. Neurosci..

[65]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[66]  K. Kendrick,et al.  A Brain‐wide association study of DISC1 genetic variants reveals a relationship with the structure and functional connectivity of the precuneus in schizophrenia , 2014, Human brain mapping.

[67]  Leonhard Schilbach,et al.  Towards a second-person neuropsychiatry , 2016, Philosophical Transactions of the Royal Society B: Biological Sciences.

[68]  P. Fox,et al.  Introspective Minds: Using ALE Meta-Analyses to Study Commonalities in the Neural Correlates of Emotional Processing, Social & Unconstrained Cognition , 2012, PloS one.

[69]  Karthik Ramakrishnan Sreenivasan,et al.  Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity , 2014, NeuroImage.

[70]  J. Os,et al.  Attribution style and psychosis: evidence for an externalizing bias in patients but not in individuals at high risk , 2006, Psychological Medicine.

[71]  Michael F Land,et al.  Do we have an internal model of the outside world? , 2014, Philosophical Transactions of the Royal Society B: Biological Sciences.

[72]  V. Gallese,et al.  Altered brain long-range functional interactions underlying the link between aberrant self-experience and self-other relationship in first-episode schizophrenia. , 2014, Schizophrenia bulletin.

[73]  Michael F. Green,et al.  Social and nonsocial cognition in bipolar disorder and schizophrenia: relative levels of impairment. , 2013, The American journal of psychiatry.

[74]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[75]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[76]  T. Fuchs Melancholia as a Desynchronization: Towards a Psychopathology of Interpersonal Time , 2001, Psychopathology.

[77]  S. Kapur Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. , 2003, The American journal of psychiatry.

[78]  D. Mathalon,et al.  Symptom dimensions and functional impairment in early psychosis: More to the story than just negative symptoms , 2013, Schizophrenia Research.

[79]  J. Klosterkötter,et al.  Diagnosing schizophrenia in the initial prodromal phase , 2000, Schizophrenia Research.

[80]  F. Španiel,et al.  Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory , 2014, Front. Behav. Neurosci..

[81]  G. Dimaggio,et al.  An intersubjective perspective on negative symptoms of schizophrenia: Implications of simulation theory , 2007, Cognitive neuropsychiatry.

[82]  B Giesbrecht,et al.  Neural mechanisms of top-down control during spatial and feature attention , 2003, NeuroImage.