Dysbindin gene variability is associated with cognitive abnormalities in first-episode non-affective psychosis

Abstract

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.

Keywords:

• dysbindin
• DTNBP1
• cognition
• psychosis
• schizophrenia
• first-episode

Acknowledgements

No pharmaceutical company supplied any financial support towards it. The study, designed and directed by I M, B C-F and Jose Luis Vazquez-Barquero (JL V-B), conformed to international standards for research ethics and was approved by the local institutional review board.

We wish to thank the PAFIP researchers who helped with data collection and specially acknowledge Cesar González-Blanch, Obdulia Martinez and Gema Pardo for data collection and David Torrellas for their assistance in imaging analysis. In addition, we acknowledge the participants and their families for enrolling in this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The present study was performed at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos III [PI020499], [PI050427], [PI060507], SENY Fundació Research Grant CI [2005-0308007] and Fundación Marqués de Valdecilla [API07/011].