Association between DBH 19bp insertion/deletion polymorphism and cognition in first-episode schizophrenic patients
Many genes associated with dopamine (DA) and norepinephrine (NE) systems influence cognitive deficits of schizophrenia patients, but one key enzyme is dopamine beta-hydroxylase (DBH), which converts DA to NE and whose activity and levels are under strong genetic control. This study examines the association of the 19 bp insertion/deletion (Ins/Del) polymorphism in the 5′ flank of the DBH gene with cognitive deficits in first-episode schizophrenic patients (FEP). We assessed the cognitive function in 195 FEP and 304 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The 19 bp Ins/Del polymorphism of DBH gene was genotyped. Our results showed that the allelic and genotypic frequencies of the 19 bp Ins/Del polymorphism significantly differed between FEP and healthy controls (both p < 0.05). Cognitive test scores were significantly lower in FEP than healthy controls on all scales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05). Immediate memory abilities significantly differed by genotype (p < 0.05) but not genotype × diagnosis. Immediate memory score was lower in FEP with DBH5′-Del/Del genotype (61.3 ± 17.2) than those with DBH5′-Ins/Ins genotype (68.6 ± 16.2; p < 0.05). The 19 bp Del allele was associated with poorer immediate memory performance than the Ins allele in FEP (p < 0.05). However, healthy controls did not show any differences in cognitive function indices between the Ins and Del for either the allele or genotype of the 19 bp Ins/Del polymorphism. Our findings suggest that the DBH5′-Ins/Del polymorphism may play a role in susceptibility to FEP. The DBH5′-Ins/Del polymorphism may also influence immediate memory in FEP. Moreover, FEP had poorer cognitive function than healthy controls in all examined cognitive domains except for the visuospatial/constructional index.
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