title: Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome.
abstract: 22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal pole. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a 'developmental-disconnection' hypothesis of symptom development in this disorder.
authors.affiliation: Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schreiner
authors.affiliation: Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Karlsgodt
authors.affiliation: Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Lucina Q
authors.initials: LQ
authors.lastname: Uddin
authors.affiliation: Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Chow
authors.affiliation: Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Eliza
authors.initials: E
authors.lastname: Congdon
authors.affiliation: Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jalbrzikowski
authors.affiliation: Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA Interdepartmental Neuroscience Program, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, Department of Psychiatry, Feinstein Institute for Medical Research, Manhasset, NY 11030, Zucker Hillside Hospital, Glen Oaks, NY 11004, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 and Department of Psychology, University of California, Los Angeles, CA 90095, USA cbearden@mednet.ucla.edu.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D004062:DiGeorge Syndrome / Q000473:pathology* / Q000523:psychology*; D005260:Female; D006179:Gyrus Cinguli / Q000098:blood supply / Q000254:growth & development / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D012919:Social Behavior; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: dysconnectivity; functional MRI; resting state; velocardiofacial syndrome
references.citation: Arch Gen Psychiatry. 1995 Jan;52(1):61-71
references.pmid: 7811163
references.citation: J Autism Dev Disord. 2000 Jun;30(3):205-23
references.pmid: 11055457
references.citation: Neuroimage. 2006 Feb 15;29(4):1359-67
references.pmid: 16260155
references.citation: J Autism Dev Disord. 2003 Aug;33(4):427-33
references.pmid: 12959421
references.citation: Neuropharmacology. 2013 May;68:157-73
references.pmid: 23098994
references.citation: Brain Res. 2010 Feb 8;1313:202-14
references.pmid: 20004180
references.citation: Annu Rev Clin Psychol. 2012;8:49-76
references.pmid: 22224834
references.citation: Cereb Cortex. 2013 Jan;23(1):127-38
references.pmid: 22275481
references.citation: Dev Sci. 2011 Jul;14(4):738-51
references.pmid: 21676094
references.citation: Int J Dev Neurosci. 2011 May;29(3):259-81
references.pmid: 20920576
references.citation: Biol Psychiatry. 2007 Aug 1;62(3):270-3
references.pmid: 17336944
references.citation: Biol Psychiatry. 2009 Jan 1;65(1):63-74
references.pmid: 18996505
references.citation: Nature. 2010 Nov 11;468(7321):187-93
references.pmid: 21068826
references.citation: Schizophr Res. 2011 Aug;130(1-3):86-93
references.pmid: 21458238
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18601-6
references.pmid: 23091025
references.citation: Schizophr Res. 2012 Dec;142(1-3):99-107
references.pmid: 23122739
references.citation: PLoS One. 2011;6(9):e25423
references.pmid: 21980454
references.citation: Trends Cogn Sci. 2007 Apr;11(4):153-7
references.pmid: 17300981
references.citation: Neurosci Biobehav Rev. 2009 Mar;33(3):279-96
references.pmid: 18824195
references.citation: Neuroimage. 2008 Feb 15;39(4):1877-85
references.pmid: 18083565
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82
references.pmid: 11209064
references.citation: Neuroimage. 2010 Aug 1;52(1):290-301
references.pmid: 20385244
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13848-53
references.pmid: 16945915
references.citation: Nat Rev Neurosci. 2010 Jun;11(6):402-16
references.pmid: 20485365
references.citation: Schizophr Res. 2012 Aug;139(1-3):33-9
references.pmid: 22704643
references.citation: Front Syst Neurosci. 2010 May 21;4:21
references.pmid: 20577585
references.citation: Hum Brain Mapp. 2007 Jun;28(6):533-42
references.pmid: 17427209
references.citation: Nature. 2010 Apr 1;464(7289):763-7
references.pmid: 20360742
references.citation: Neurol Sci. 2011 Oct;32(5):773-85
references.pmid: 21667095
references.citation: Front Hum Neurosci. 2012 Jun 21;6:184
references.pmid: 22737116
references.citation: Front Hum Neurosci. 2012 Nov 06;6:301
references.pmid: 23133413
references.citation: Funct Neurol. 2011 Jan-Mar;26(1):37-43
references.pmid: 21693087
references.citation: J Autism Dev Disord. 1994 Oct;24(5):659-85
references.pmid: 7814313
references.citation: PLoS Comput Biol. 2009 May;5(5):e1000381
references.pmid: 19412534
references.citation: Hum Brain Mapp. 2009 Feb;30(2):625-37
references.pmid: 18219617
references.citation: Biol Psychiatry. 2013 Aug 1;74(3):212-9
references.pmid: 23375976
references.citation: Neuroimage. 2010 Oct 15;53(1):247-56
references.pmid: 20621638
references.citation: Neuron. 2012 Sep 6;75(5):904-15
references.pmid: 22958829
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8
references.pmid: 12506194
references.citation: Front Syst Neurosci. 2010 Apr 06;4:8
references.pmid: 20407579
references.citation: Neuroimage. 2012 Feb 1;59(3):2142-54
references.pmid: 22019881
references.citation: Am J Psychiatry. 2009 Aug;166(8):891-9
references.pmid: 19605539
references.citation: NMR Biomed. 1997 Jun-Aug;10(4-5):165-70
references.pmid: 9430343
references.citation: Schizophr Res. 2012 Dec;142(1-3):77-82
references.pmid: 23043872
references.citation: Autism Res. 2012 Dec;5(6):407-18
references.pmid: 22962003