title: Intrinsic Connectivity Network-Based Classification and Detection of Psychotic Symptoms in Youth With 22q11.2 Deletions.
abstract: 22q11.2 Deletion syndrome (22q11DS) is a genetic disorder associated with numerous phenotypic consequences and is one of the greatest known risk factors for psychosis. We investigated intrinsic-connectivity-networks (ICNs) as potential biomarkers for patient and psychosis-risk status in 2 independent cohorts, UCLA (33 22q11DS-participants, 33 demographically matched controls), and Syracuse (28 22q11DS, 28 controls). After assessing group connectivity differences, ICNs from the UCLA cohort were used to train classifiers to distinguish cases from controls, and to predict psychosis risk status within 22q11DS; classifiers were subsequently tested on the Syracuse cohort. In both cohorts we observed significant hypoconnectivity in 22q11DS relative to controls within anterior cingulate (ACC)/precuneus, executive, default mode (DMN), posterior DMN, and salience networks. Of 12 ICN-derived classifiers tested in the Syracuse replication-cohort, the ACC/precuneus, DMN, and posterior DMN classifiers accurately distinguished between 22q11DS and controls. Within 22q11DS subjects, connectivity alterations within 4 networks predicted psychosis risk status for a given individual in both cohorts: the ACC/precuneus, DMN, left executive, and salience networks. Widespread within-network-hypoconnectivity in large-scale networks implicated in higher-order cognition may be a defining characteristic of 22q11DS during adolescence and early adulthood; furthermore, loss of coherence within these networks may be a valuable biomarker for individual prediction of psychosis-risk in 22q11DS.
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA.|Interdepartmental Neuroscience Program, University of California, Los Angeles, CA 90095, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Schreiner
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Forsyth
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Karlsgodt
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA.
authors.forename: Ariana E
authors.initials: AE
authors.lastname: Anderson
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Nurit
authors.initials: N
authors.lastname: Hirsh
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Kushan
authors.affiliation: Department of Psychology, University of Miami, Coral Gables, FL 33124, USA.|Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Lucina Q
authors.initials: LQ
authors.lastname: Uddin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, New York, NY 13210, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Mattiacio
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, New York, NY 13210, USA.
authors.forename: Ioana L
authors.initials: IL
authors.lastname: Coman
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, New York, NY 13210, USA.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Kates
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA 90095, USA.|Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D063132:Connectome; D004062:DiGeorge Syndrome / Q000150:complications*; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009038:Motion; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000145:classification / Q000209:etiology / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: intrinsic connectivity networks; machine learning; psychosis; resting state functional MRI; velocardiofacial syndrome