A genetic variation in the dysbindin gene(DTNBP1)is associated with memory performance in healthy controls

Abstract

Schizophrenia is a common psychiatric disorder characterized by disturbances of cognition, emotion and social functioning. There are few studies investigating a possible genetic basis for the underlying mechanism of cognitive dysfunctions. A genetic variation in the dysbindin gene (DTNBP1: dystrobrevin binding protein 1), a susceptibility gene for schizophrenia, has been reported to be associated with general cognitive ability and cognitive decline in patients with schizophrenia. Although profound disturbances of memory performance are observed in schizophrenia, only one study has reported a relationship between this gene and spatial working memory in a Caucasian population. We examined a possible association between a protective haplotype of DTNBP1 for developing schizophrenia and memory performance measured by the Wechsler Memory Scale-Revised (WMS-R) and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) in 165 healthy volunteers and 70 patients with schizophrenia in a Japanese population. Healthy controls that carry the protective haplotype showed higher performance in several memory domains measured by the WMS-R than those who did not. Genotype effect on memory performance was not observed in patients with schizophrenia. This haplotype did not affect IQ and its sub-scores as measured by the Wechsler Adult Intelligence Scale-Revised in both groups. These data suggest that DTNBP1 may have impact on parts of memory functions.

Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila

“…An increasing number of studies suggest that genetic variation in DTNBP1 in normal human populations affects verbal and visual memories as well as working memory (35,36). This association is supported by studies on the sandy mouse, which is defective in a range of memory tasks, including spatial memory, novel object recognition, and contextual fear conditioning (12,13).…”

Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia

“…The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia, 1 and the dysbindin-1 gene is also associated with cognitive functions. [2][3][4] Furthermore, the Sandy mouse, which expresses no dysbindin-1, has been reported to have behavioral abnormalities, cognitive deficits and a synaptic dysfunction that is related to the pathophysiology of schizophrenia. [5][6][7] Identified risk variants of NRG-1 are associated with the reduced white matter volume that is observed in schizophrenic brains.…”

Contribution of nonprimate animal models in understanding the etiology of schizophrenia

“…304 Similarly, a protective haplotype of DTNBP1 was found to increase memory performance in healthy controls, although it had no performance effect in patients with schizophrenia. 305 Recently, there has been a proliferation of animal model studies that have examined Dtnbp1 in the sandy mouse, which does not express the Dtnbp1 gene. 306 Studies have shown that Dtnbp1 knockout mice display reduced social inter action, impairments in long-term memory retention, spatial memory and working memory, as well as hyperactivity.…”