Introduction: Dystrobrevin-binding protein 1 gene (dysbindin or DTNBP1) has been associated with schizophrenia and cognitive performance. Its expression in areas implicated in cognition such as the dorsolateral prefrontal cortex, as well as its role in dopaminergic and glutamatergic system, has been replicated by several studies. The main aim of this study was to examine the association between DTNBP1 variability and cognitive performance in a sample of 238 patients with a first episode of a non-affective psychosis.
Methods: Patients, and a comparison sample of 47 healthy subjects, completed an extensive neuropsychological battery. Five single nucleotide polymorphisms (SNPs) within DTNBP1 (rs2619528, rs2619538, rs3213207, rs2619539 and rs760761) and three haplotypes (GACAC, GAGAC and GTGAC) were analysed.
Results: In the group of patients, we found a significant association between two of the DTNBP1 SNPs and one of the haplotypes (rs2619539, rs3213207 and GACAC) and a measure of premorbid IQ [Wechsler Adult Intelligence Scale-3rd Edition (WAIS-III) Vocabulary subtest]. Moreover, one of these SNPs, rs2619539, was also associated with our measure of working memory (WAIS-III Backward digits subtest) and two haplotypes, GAGAC and GTGAC, with our measure of verbal memory (Rey Auditory Verbal Learning Test), of visual memory (Rey Complex Figure Test) in the case of GAGAC, and of speed of processing (WAIS-III Digit Symbol-coding) in the case of GTGAC.
Conclusions: Our findings add further evidence suggesting an association between dysbindin gene variability and cognitive abnormalities in schizophrenia, providing preliminary evidence of this association since the time of illness onset among minimally medicated patients.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1080/13546805.2014.991780 | DOI Listing |
Int J Mol Sci
November 2024
Department of Psychology, Binghampton University-State University of New York, Binghampton, NY 13902, USA.
Elevated risk for schizophrenia is associated with a variation in the gene encoding dysbindin-1, which may underpin cognitive impairments in this prevalent neuropsychiatric disorder. The cognitive symptoms of schizophrenia involve anomalies in glutamate and dopamine signaling, particularly within the prefrontal cortex (PFC). Indeed, mice with mutations exhibit spatial and working memory deficits that are associated with deficits in glutamate release and NMDA receptor function as determined by slice electrophysiology.
View Article and Find Full Text PDFSci Rep
July 2024
Douglas Hospital Research Centre, Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montreal, QC, H4H 1R3, Canada.
Dysbindin-1, a protein encoded by the schizophrenia susceptibility gene DTNBP1, is reduced in the hippocampus of schizophrenia patients. It is expressed in various cellular populations of the brain and implicated in dopaminergic and glutamatergic transmission. To investigate the impact of reduced dysbindin-1 in excitatory cells on hippocampal-associated behaviors and synaptic transmission, we developed a conditional knockout mouse model with deletion of dysbindin-1 gene in CaMKIIα expressing cells.
View Article and Find Full Text PDFMol Psychiatry
September 2024
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123, Catania, Italy.
Cognitive dysfunctions are core-enduring symptoms of schizophrenia, with important sex-related differences. Genetic variants of the DTBPN1 gene associated with reduced dysbindin-1 protein (Dys) expression negatively impact cognitive functions in schizophrenia through a functional epistatic interaction with Catechol-O-methyltransferase (COMT). Dys is involved in the trafficking of dopaminergic receptors, crucial for prefrontal cortex (PFC) signaling regulation.
View Article and Find Full Text PDFOphthalmic Genet
June 2024
Department of Ophthalmology, Centro Hospitalar Universitário de São João, Porto, Portugal.
Int J Mol Sci
July 2023
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!