title: Connectome-wide network analysis of youth with Psychosis-Spectrum symptoms.
abstract: Adults with psychotic disorders have dysconnectivity in critical brain networks, including the default mode (DM) and the cingulo-opercular (CO) networks. However, it is unknown whether such deficits are present in youth with less severe symptoms. We conducted a multivariate connectome-wide association study examining dysconnectivity with resting state functional magnetic resonance imaging in a population-based cohort of 188 youths aged 8-22 years with psychosis-spectrum (PS) symptoms and 204 typically developing (TD) comparators. We found evidence for multi-focal dysconnectivity in PS youths, implicating the bilateral anterior cingulate, frontal pole, medial temporal lobe, opercular cortex and right orbitofrontal cortex. Follow-up seed-based and network-level analyses demonstrated that these results were driven by hyper-connectivity among DM regions and diminished connectivity among CO regions, as well as diminished coupling between frontal and DM regions. Collectively, these results provide novel evidence for functional dysconnectivity in PS youths, which show marked correspondence to abnormalities reported in adults with established psychotic disorders.
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Satterthwaite
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Vandekar
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Wolf
authors.affiliation: Departments of Bioengineering and Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Bassett
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ruparel
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, USA.|Center for the Developing Brain, Child Mind Institute, New York, NY, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Shehzad
authors.affiliation: Center for the Developing Brain, Child Mind Institute, New York, NY, USA.|Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research; Orangeburg, NY, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Craddock
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Shinohara
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Moore
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Gennatas
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jackson
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Roalf
authors.affiliation: Center for the Developing Brain, Child Mind Institute, New York, NY, USA.|Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research; Orangeburg, NY, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Milham
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Philadelphia Veterans Administration Medical Center, Philadelphia, PA, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gur
mesh_terms: D000293:Adolescent; D001931:Brain Mapping; D002648:Child; D063132:Connectome; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011618:Psychotic Disorders / Q000473:pathology*; D055815:Young Adult