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

Authors

  • Mar Fatjó-Vilas,

    1. Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona. Institut de Biomedicina de la Universitat de Barcelona (IBUB). Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
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  • Sergi Papiol,

    1. Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona. Institut de Biomedicina de la Universitat de Barcelona (IBUB). Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
    2. Max Planck Institute of Experimental Medicine, Clinical Neuroscience Division and Neurogenetics Department. Göttingen, Germany
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  • Gemma Estrada,

    1. Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona. Institut de Biomedicina de la Universitat de Barcelona (IBUB). Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
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  • Igor Bombín,

    1. Departamento de Neuropsicología, Centro de Rehabilitación Neurológica de Reintegra, Oviedo, Spain
    2. Departamento de Psicología. Universidad de Oviedo, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Oviedo, Spain
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  • Victor Peralta,

    1. Sección de Psiquiatría B, Complejo Hospitalario de Navarra. Pamplona, Spain
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  • Araceli Rosa,

    1. Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona. Institut de Biomedicina de la Universitat de Barcelona (IBUB). Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
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  • Mara Parellada,

    1. Unidad de Adolescentes, Servicio de Psiquiatría, Hospital General Universitario Gregorio Marañón, Madrid. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Madrid, Spain
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  • Salvador Miret,

    1. Centre de Salut Mental de Lleida, Servei de Salut Mental i Addiccions, Hospital Santa Maria. Lleida, Spain
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  • María Martín,

    1. Àrea d'Adolescents. Complex Assistencial en Salut Mental, Benito Menni. Sant Boi de Llobregat, Barcelona, Spain
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  • Luisa Lázaro,

    1. Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
    2. Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS). Barcelona, Spain
    3. Departament de Psiquiatria i Psicologia, Universitat de Barcelona. Barcelona, Spain
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  • Sílvia Campanera,

    1. Centre de Salut Mental de Lleida, Servei de Salut Mental i Addiccions, Hospital Santa Maria. Lleida, Spain
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  • Ma José Muñoz,

    1. Àrea d'Adolescents. Complex Assistencial en Salut Mental, Benito Menni. Sant Boi de Llobregat, Barcelona, Spain
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  • Sara Lera-Miguel,

    1. Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
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  • Bárbara Arias,

    1. Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona. Institut de Biomedicina de la Universitat de Barcelona (IBUB). Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
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  • Ma Eulalia Navarro,

    1. Àrea d'Adolescents. Complex Assistencial en Salut Mental, Benito Menni. Sant Boi de Llobregat, Barcelona, Spain
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  • Josefina Castro-Fornieles,

    1. Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
    2. Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS). Barcelona, Spain
    3. Departament de Psiquiatria i Psicologia, Universitat de Barcelona. Barcelona, Spain
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  • Manuel J. Cuesta,

    1. Sección de Psiquiatría B, Complejo Hospitalario de Navarra. Pamplona, Spain
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  • Celso Arango,

    1. Unidad de Adolescentes, Servicio de Psiquiatría, Hospital General Universitario Gregorio Marañón, Madrid. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Madrid, Spain
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  • Lourdes Fañanás

    Corresponding author
    1. Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona. Institut de Biomedicina de la Universitat de Barcelona (IBUB). Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Barcelona, Spain
    • Unitat d'Antropologia, Facultat de Biologia, Departament de Biologia Animal, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Catalonia, Spain.
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  • Please cite this article as follows: Fatjó-Vilas M, Papiol S, Estrada G, Bombín I, Peralta V, Rosa A, Parellada M, Miret S, Martín M, Lázaro L, Campanera S, Muñoz MJ, Lera S, Arias B, Navarro ME, Castro-Fornieles J, Cuesta MJ, Arango C, Fañanás L. 2011. Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis. Am J Med Genet Part B 156:322–333.

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. © 2011 Wiley-Liss, Inc.

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