The PFC and the hippocampus have been shown to play a fundamental role in cognition, and studies in dysbindin-1 null mice have shown alterations in NMDAR located in pyramidal neurons as well as perturbation in LTP and cognitive deficits.
These results show promise for counteracting the cognitive impairments seen in neuropsychiatric disorders and may shed light on the role of dysbindin-1.
Together, results indicate an important role of dysbindin-1 in neuronal activity induced SREBP1 and ARC, which could be related to cognitive deficits in schizophrenia.
Members of the DAPC and dysbindin are abnormally expressed in the brain of Duchenne Muscular Dystrophy (DMD) patients, which has been associated with cognitive impairments.
To date, however, only the genes encoding apolipoprotein E (APOE) and possibly catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF) and dystrobrevin binding protein 1 (DTNBP1) have repeatedly been associated in candidate gene studies with cognitive decline or with cognitive ability in older individuals.
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.
Given the predominantly post-synaptic localization of dysbindin-1C and known post-synaptic effects of dysbindin-1 reductions in the rodent equivalent of the DLPFC, the present findings suggest that decreased dysbindin-1C in the DLPFC may contribute to the cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction in fast-spiking interneurons.
In the Finnish population, DTNBP1 gene is associated with a schizophrenia phenotype characterized by prominent negative symptoms, generalized cognitive impairment, and few mood symptoms.
Genetic variation in dysbindin 1 (DTNBP1) gene region tagged by SNP rs1018381 exhibits a linkage with cognitive deficits in patients with schizophrenia and healthy subjects.