title: Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome.
abstract: 22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jalbrzikowski
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California Marina del Rey, CA, USA.
authors.forename: Julio E
authors.initials: JE
authors.lastname: Villalon-Reina
authors.affiliation: Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research Manhasset, NY, USA ; Division of Psychiatric Research, Zucker Hillside Hospital Glen Oaks, NY, USA ; Psychiatry, Hofstra Northshore-LIJ School of Medicine Hempstead, NY, USA.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Karlsgodt
authors.affiliation: Department of Biostatistics, School of Public Health, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Damla
authors.initials: D
authors.lastname: Senturk
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Chow
authors.affiliation: Imaging Genetics Center, Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California Marina del Rey, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Los Angeles, CA, USA ; Department of Psychology, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
keywords: DTI; axial diffusivity; prodromal; psychosis; radial diffusivity; schizophrenia; theory of mind; velocardiofacial syndrome