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World J Biol Psychiatry. 2016;17(2):129-39. doi: 10.3109/15622975.2015.1093658. Epub 2015 Dec 24.

Involvement of NRN1 gene in schizophrenia-spectrum and bipolar disorders and its impact on age at onset and cognitive functioning.

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a Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona , Barcelona , Spain ; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain;
b Instituto De Salud Carlos III, Centro De Investigación Biomédica En Red De Salud Mental (CIBERSAM) , Madrid , Spain ;
c FIDMAG Germanes Hospitalàries, Research Foundation , Barcelona , Spain ;
d Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona , Barcelona , Spain ;
e Institut d'investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Departament de Psiquiatria i Psicobiologia Clínica, Facultat de Medicina, Universitat de Barcelona , Barcelona , Spain ;
f Servicio de Psiquiatría del Niño y del Adolescente , Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Gregorio Marañón (IiSGM); Departamento de Psiquiatría, Facultad de Medicina, Universidad Complutense , Madrid , Spain ;
g Psychiatry Service, University Hospital of Alava-Santiago, EMBREC, EHU/UPV University of the Basque Country, Kronikgune , Vitoria , Spain ;
h Centre de Salut Mental d'Adults de Lleida, Servei de Psiquiatria, Salut Mental i Addiccions, Hospital Universitari Santa Maria de Lleida , Lleida , Spain ;
i Àrea d'Adolescents, Complex Assistencial en Salut Mental Benito Menni, Sant Boi De Llobregat , Spain ;
j Departament de Psicologia Bàsica , Clínica i Psicobiologia, Facultat de Ciències de la Salut, Universitat Jaume I , Castelló , Spain ;
k Servicio de Psiquiatría, Complejo Hospitalario de Navarra, Pamplona Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA) , Pamplona , Spain.



Neuritin 1 gene (NRN1) is involved in neurodevelopment processes and synaptic plasticity and its expression is regulated by brain-derived neurotrophic factor (BDNF). We aimed to investigate the association of NRN1 with schizophrenia-spectrum disorders (SSD) and bipolar disorders (BPD), to explore its role in age at onset and cognitive functioning, and to test the epistasis between NRN1 and BDNF.


The study was developed in a sample of 954 SSD/BPD patients and 668 healthy subjects. Genotyping analyses included 11 SNPs in NRN1 and one functional SNP in BDNF.


The frequency of the haplotype C-C (rs645649-rs582262) was significantly increased in patients compared to controls (P = 0.0043), while the haplotype T-C-C-T-C-A (rs3763180-rs10484320-rs4960155-rs9379002-rs9405890-rs1475157) was more frequent in controls (P = 3.1 × 10(-5)). The variability at NRN1 was nominally related to changes in age at onset and to differences in intelligence quotient, in SSD patients. Epistasis between NRN1 and BDNF was significantly associated with the risk for SSD/BPD (P = 0.005).


Results suggest that: (i) NRN1 variability is a shared risk factor for both SSD and BPD, (ii) NRN1 may have a selective impact on age at onset and intelligence in SSD, and (iii) the role of NRN1 seems to be not independent of BDNF.


BDNF; NRN1; Schizophrenia-spectrum and bipolar disorders; age at onset; intelligence

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