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.