title: Characterizing thalamo-cortical disturbances in schizophrenia and bipolar illness.
abstract: Schizophrenia is a devastating neuropsychiatric syndrome associated with distributed brain dysconnectivity that may involve large-scale thalamo-cortical systems. Incomplete characterization of thalamic connectivity in schizophrenia limits our understanding of its relationship to symptoms and to diagnoses with shared clinical presentation, such as bipolar illness, which may exist on a spectrum. Using resting-state functional magnetic resonance imaging, we characterized thalamic connectivity in 90 schizophrenia patients versus 90 matched controls via: (1) Subject-specific anatomically defined thalamic seeds; (2) anatomical and data-driven clustering to assay within-thalamus dysconnectivity; and (3) machine learning to classify diagnostic membership via thalamic connectivity for schizophrenia and for 47 bipolar patients and 47 matched controls. Schizophrenia analyses revealed functionally related disturbances: Thalamic over-connectivity with bilateral sensory-motor cortices, which predicted symptoms, but thalamic under-connectivity with prefrontal-striatal-cerebellar regions relative to controls, possibly reflective of sensory gating and top-down control disturbances. Clustering revealed that this dysconnectivity was prominent for thalamic nuclei densely connected with the prefrontal cortex. Classification and cross-diagnostic results suggest that thalamic dysconnectivity may be a neural marker for disturbances across diagnoses. Present findings, using one of the largest schizophrenia and bipolar neuroimaging samples to date, inform basic understanding of large-scale thalamo-cortical systems and provide vital clues about the complex nature of its disturbances in severe mental illness.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA NIAAA Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06519, USA Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Anticevic
authors.affiliation: Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cole
authors.affiliation: Department of Psychology, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Grega
authors.initials: G
authors.lastname: Repovs
authors.affiliation: Department of Neurobiology, Department of Physics, Yale University, New Haven, CT 06510, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Murray
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA.
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Brumbaugh
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA Oxford University, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK and.
authors.forename: Anderson M
authors.initials: AM
authors.lastname: Winkler
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA University Psychiatric Hospital Vrapce, University of Zagreb, Zagreb 10000, Croatia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Savic
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA NIAAA Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06519, USA Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Department of Neurobiology, Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA.
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, CT 06106, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000473:pathology*; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000473:pathology*; D013788:Thalamus / Q000098:blood supply / Q000473:pathology*; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: bipolar illness; connectivity; resting state; schizophrenia; thalamus