title: Neurotrophins role in depressive symptoms and executive function performance: Association analysis of NRN1 gene and its interaction with BDNF gene in a non-clinical sample.
abstract: Neuritin-1 is a neurotrophic factor involved in synaptic plasticity that has been associated with depressive disorders, schizophrenia and cognitive performance. The study of genotype-phenotype relationships in healthy individuals is a useful framework to investigate the etiology of brain dysfunctions. We therefore aimed to investigate in a non-clinical sample whether NRN1 gene contributes to the psychopathological profile, with a particular focus on the clinical dimensions previously related to the NRN1 gene (i.e. depressive and psychotic). Furthermore, we aimed to analyze: i) the role of NRN1 on executive functions, ii) whether the association between either NRN1-psychopathological profile or NRN1-cognitive performance is moderated by the BDNF gene.
  
  
  
  The sample comprised 410 non-clinical subjects who filled in the self-reported Brief Symptom Inventory (BSI) and were assessed for executive performance (Verbal Fluency, Wisconsin Card Sorting Test (WCST) and Letter-Number subscale (WAIS-III)). Genotyping included nine SNPs in NRN1 and one in BDNF.
  
  
  
  i) GG homozygotes (rs1475157-NRN1) showed higher scores on BSI depressive dimension and on total scores compared to A carriers (corrected p-values: 0.0004 and 0.0003, respectively). ii) a linear trend was detected between GG genotype of rs1475157 and a worse cognitive performance in WCST total correct responses (uncorrected p-value: 0.029). iii) Interaction between rs1475157-NRN1 and Val66Met-BDNF was found to modulate depressive symptoms (p=0.001, significant after correction).
  
  
  
  Moderate sample size; replication in a larger sample is needed.
  
  
  
  NRN1 is associated with depressive symptoms and executive function in a non-clinical sample. Our results also suggest that the role of NRN1 seems to be modulated by BDNF.
authors.affiliation: Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Spain, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain; Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation; Av Jordà 8, 08035 Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Prats
authors.affiliation: Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Spain, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain; Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation; Av Jordà 8, 08035 Barcelona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Arias
authors.affiliation: Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Department of Basic and Clinical Psychology and Psychobiology, Universitat Jaume I, Castelló, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Ortet
authors.affiliation: Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Department of Basic and Clinical Psychology and Psychobiology, Universitat Jaume I, Castelló, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: Ibáñez
authors.affiliation: Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Department of Psychology, Faculty of Education, Psychology and Social Work, University of Lleida, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Moya
authors.affiliation: Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Pomarol-Clotet
authors.affiliation: Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Spain, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain; Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation; Av Jordà 8, 08035 Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Fañanás
authors.affiliation: Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Spain, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain; Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; FIDMAG Germanes Hospitalàries Research Foundation; Av Jordà 8, 08035 Barcelona, Spain. Electronic address: mar.fatjovilas@ub.edu.
authors.forename: M
authors.initials: M
authors.lastname: Fatjó-Vilas
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics*; D056344:Executive Function; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009473:Neuronal Plasticity; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; Depressive symptoms; Executive function; Gene-gene interaction; General population; NRN1