title: Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis.
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.
authors.affiliation: Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Fatjó-Vilas
authors.forename: Sergi
authors.initials: S
authors.lastname: Papiol
authors.forename: Gemma
authors.initials: G
authors.lastname: Estrada
authors.forename: Igor
authors.initials: I
authors.lastname: Bombín
authors.forename: Victor
authors.initials: V
authors.lastname: Peralta
authors.forename: Araceli
authors.initials: A
authors.lastname: Rosa
authors.forename: Mara
authors.initials: M
authors.lastname: Parellada
authors.forename: Salvador
authors.initials: S
authors.lastname: Miret
authors.forename: María
authors.initials: M
authors.lastname: Martín
authors.forename: Luisa
authors.initials: L
authors.lastname: Lázaro
authors.forename: Sílvia
authors.initials: S
authors.lastname: Campanera
authors.forename: Ma José
authors.initials: MJ
authors.lastname: Muñoz
authors.forename: Sara
authors.initials: S
authors.lastname: Lera-Miguel
authors.forename: Bárbara
authors.initials: B
authors.lastname: Arias
authors.forename: Ma Eulalia
authors.initials: ME
authors.lastname: Navarro
authors.forename: Josefina
authors.initials: J
authors.lastname: Castro-Fornieles
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Cuesta
authors.forename: Celso
authors.initials: C
authors.lastname: Arango
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fañanás
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003071:Cognition / Q000502:physiology; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D035781:Siblings
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins