title: Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome.
abstract: 22q11.2 deletion syndrome is a neurogenetic disorder resulting in the deletion of over 40 genes. Up to 40% of individuals with 22q11.2DS develop schizophrenia, though little is known about the underlying mechanisms. We hypothesized that allelic variation in functional polymorphisms in seven genes unique to the deleted region would affect lobar brain volumes, which would predict risk for psychosis in youth with 22q11.2DS. Participants included 56 individuals (30 males) with 22q11.2DS. Anatomic MR images were collected and processed using Freesurfer. Participants were genotyped for 10 SNPs in the COMT, DGCR8, GNB1L, PIK4CA, PRODH, RTN4R, and ZDHHC8 genes. All subjects were assessed for ultra high risk symptoms of psychosis. Allelic variation of the rs701428 SNP of RTN4R was significantly associated with volumetric differences in gray matter of the lingual gyrus and cuneus of the occipital lobe. Moreover, occipital gray matter volumes were robustly associated with ultra high risk symptoms of psychosis in the presence of the G allele of rs701428. Our results suggest that RTN4R, a relatively under-studied gene at the 22q11 locus, constitutes a susceptibility gene for psychosis in individuals with this syndrome through its alteration of the architecture of the brain. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Carlie A
authors.initials: CA
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Jason
authors.initials: J
authors.lastname: Karelis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.|Department of Neuroscience, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Middleton
authors.affiliation: Department of Neuroscience, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Karen
authors.initials: K
authors.lastname: Gentile
authors.affiliation: Department of Computer Science, SUNY Oswego, Oswego, New York.
authors.forename: Ioana L
authors.initials: IL
authors.lastname: Coman
authors.affiliation: Department of Psychiatry, University of Washington, Seattle, Washington.
authors.forename: Petya D
authors.initials: PD
authors.lastname: Radoeva
authors.affiliation: Department of Radiology, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Rashi
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Wanda P
authors.initials: WP
authors.lastname: Fremont
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.|Department of Psychology, Syracuse University, Syracuse, New York.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Antshel
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Kates
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000523:psychology*; D000293:Adolescent; D000483:Alleles; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics* / Q000523:psychology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D066128:Gray Matter; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009445:Neuroanatomy; D065886:Neurodevelopmental Disorders / Q000235:genetics; D000070816:Nogo Receptor 1 / Q000235:genetics* / Q000502:physiology; D009778:Occipital Lobe; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000209:etiology / Q000235:genetics* / Q000523:psychology; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics; D055815:Young Adult
chemical_list: D000070816:Nogo Receptor 1; C486580:RTN4R protein, human; D002394:Catechol O-Methyltransferase
keywords: Freesurfer; RTN4R; axonal development; schizophrenia; velo-cardio-facial syndrome