Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis

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Publication Details

Author list: Bombin I
Publisher: Wiley: 12 months
Publication year: 2011
Volume number: 156
Issue number: 3
Start page: 322
End page: 333
Number of pages: 12
ISSN: 1552-4841
Languages: English-Great Britain (EN-GB)


Abstract

Dysbindin-1 is a relatively ubiquitous protein in the brain which is
involved in the modulation of synaptic homeostasis. The dysbindin-1 gene
(DTNBP1) has been associated with schizophrenia and bipolar disorder
diagnoses. However, its contribution to the severity of the clinical and
neurocognitive expression of these disorders remains controversial. We
aimed to explore the association between DTNBP1 and the phenotypes which
are more directly linked with the underlying biology, such as age at
onset and neurocognitive impairment. The present family sample comprised
894 Caucasian individuals: 268 patients affected by functional
psychosis [58% with illness onset before 18 years, mean age at onset
(SD): 14.71 (2.10)], 483 parents and 143 siblings. Ten DTNBP1 single
nucleotide polymorphisms were genotyped in all individuals and their
transmission disequilibrium was tested in relation to: (i) the risk for
psychosis; (ii) patients' age at onset; and (iii) familial
neurocognitive performance (including IQ estimation and executive
functioning). In early-onset families a 5-marker haplotype encompassing
exons 2-4 and the surrounding introns was significantly over-transmitted
to cases, while in adult-onset families two haplotypes corresponding to
the region between introns 4 and 7 were over-transmitted to cases.
Estimated IQ was associated with the rs760666 marker in the whole
sample, whereas a significant association between executive functioning
and the rs2619522 marker appeared in early-onset families. Our findings
confirm the role of the dysbindin-1 gene in the risk for functional
psychosis and show a differential haplotypic risk pattern in families
with early as opposed to adult onset in the affected offspring


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Last updated on 2019-13-08 at 00:45