title: Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the Premorbid Adjustment Scale (PAS).
abstract: Straub et al. (2002) recently identified the 6p22.3 gene dysbindin (DTNBP1) through positional cloning as a schizophrenia susceptibility gene. We studied a rare cohort of 102 children with onset of psychosis before age 13. Standardized ratings of early development, medication response, neuropsychological and cognitive performance, premorbid dysfunction and clinical follow-up were obtained. Fourteen SNPs were genotyped in the gene DTNBP1. Family-based pairwise and haplotype transmission disequilibrium test (TDT) analysis with the clinical phenotype, and quantitative transmission disequilibrium test (QTDT) explored endophenotype relationships. One SNP was associated with diagnosis (TDT p=.01). The QTDT analyses showed several significant relationships. Four adjacent SNPs were associated (p values=.0009-.003) with poor premorbid functioning. These findings support the hypothesis that this and other schizophrenia susceptibility genes contribute to early neurodevelopmental impairment.
authors.affiliation: Child Psychiatry Branch, IRP, National Institute of Mental Health, NIH, Bethesda, MD 20892-1600, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Gornick
authors.forename: A M
authors.initials: AM
authors.lastname: Addington
authors.forename: A
authors.initials: A
authors.lastname: Sporn
authors.forename: N
authors.initials: N
authors.lastname: Gogtay
authors.forename: D
authors.initials: D
authors.lastname: Greenstein
authors.forename: M
authors.initials: M
authors.lastname: Lenane
authors.forename: P
authors.initials: P
authors.lastname: Gochman
authors.forename: A
authors.initials: A
authors.lastname: Ordonez
authors.forename: R
authors.initials: R
authors.lastname: Balkissoon
authors.forename: R
authors.initials: R
authors.lastname: Vakkalanka
authors.forename: D R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: J L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: R E
authors.initials: RE
authors.lastname: Straub
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015331:Cohort Studies; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D010641:Phenotype; D011618:Psychotic Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012917:Social Adjustment; D011795:Surveys and Questionnaires
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins