Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the Premorbid Adjustment Scale (PAS).
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.
Gornick
M C
MC
Child Psychiatry Branch, IRP, National Institute of Mental Health, NIH, Bethesda, MD 20892-1600, USA.
Addington
A M
AM
Sporn
A
A
Gogtay
N
N
Greenstein
D
D
Lenane
M
M
Gochman
P
P
Ordonez
A
A
Balkissoon
R
R
Vakkalanka
R
R
Weinberger
D R
DR
Rapoport
J L
JL
Straub
R E
RE
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
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins