EXCLUSION OF CLOSE LINKAGE OF THE DOPAMINE TRANSPORTER GENE WITH SCHIZOPHRENIA SPECTRUM DISORDERS

Objective: Involvement of genetic factors in the pathogenesis of schiz ophrenia spectrum disorders has been indicated in twin, adoption, and familial aggregation studies; the pivotal role played by the dopamine transporter in dopaminergic neurotransmission makes it a candidate gen e for these disorders. Detection of close linkage between a dopamine t ransporter marker and schizophrenia spectrum disorders would strongly support the existence of causal relationships between genetic mutation s at the dopamine transporter focus and the disease phenotype. Method: The authors assessed the linkage between this gene and schizophrenia spectrum disorders by using polymorphic dopamine transporter gene mark ers in 156 subjects from 16 multiplex pedigrees with schizophrenia as well as schizophreniform, schizoaffective, and schizotypal disorders a nd mood-incongruent psychotic depression. Results: Complete (theta=0.0 ) linkage to the schizophrenia spectrum was excluded under both domina nt and recessive models. Conclusions: These results indicate that alle lic variants at the dopamine transporter focus do not provide major ge netic contributions to the etiology of schizophrenia and related disor ders in these pedigrees.