Association Study of 10 Genes Encoding Neurotrophic Factors and Their Receptors in Adult and Child Attention-Deficit/Hyperactivity Disorder

Marta Ribasés, Amaia Hervás, Josep Antoni Ramos-Quiroga, Rosa Bosch, Anna Bielsa, Xavier Gastaminza, Mònica Fernández-Anguiano, Mariana Nogueira, Núria Gómez-Barros, Sergi Valero, Mònica Gratacòs, Xavier P. Estivill, Miquel Casas, Bru Cormand, Mònica Bayés

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder that often persists into adolescence and adulthood and is characterized by inappropriate levels of inattention, hyperactivity, and/or impulsivity. Genetic and environmental factors are believed to be involved in the continuity of the disorder as well as in changes in ADHD symptomatology throughout life. Neurotrophic factors (NTFs), which participate in neuronal survival and synaptic efficiency, are strong candidates to contribute to the neuroplasticity changes that take place in the human central nervous system during childhood, adolescence, and early adulthood and might be involved in the genetic predisposition to ADHD. Methods: We performed a population-based association study in 546 ADHD patients (216 adults and 330 children) and 546 gender-matched unrelated control subjects with 183 single nucleotide polymorphisms covering 10 candidate genes that encode four neurotrophins (NGF, BDNF, NTF3, and NTF4/5), a member of the cytokine family of NTFs (CNTF), and their receptors (NTRK1, NTRK2, NTRK3, NGFR, and CNTFR). Results: The single-marker and haplotype-based analyses provided evidence of association between CNTFR and both adulthood (p = .0077, odds ratio [OR] = 1.38) and childhood ADHD (p = 9.1e-04, OR = 1.40) and also suggested a childhood-specific contribution of NTF3 (p = 3.0e-04, OR = 1.48) and NTRK2 (p = .0084, OR = 1.52) to ADHD. Conclusions: Our data suggest that variations in NTFs might be involved in the genetic susceptibility to ADHD, support the contribution of the CNTFR locus as a predisposition factor for the disorder, and suggest that NTF3 and NTRK2 might be involved in the molecular basis of the age-dependent changes in ADHD symptoms throughout life span.

Original languageEnglish
Pages (from-to)935-945
Number of pages11
JournalBiological Psychiatry
Volume63
Issue number10
DOIs
Publication statusPublished - 15 May 2008
Externally publishedYes

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Nerve Growth Factor Receptors
Attention Deficit Disorder with Hyperactivity
Genes
Nerve Growth Factors
Odds Ratio
Genetic Predisposition to Disease
Neuronal Plasticity
Impulsive Behavior
Brain-Derived Neurotrophic Factor
Nerve Growth Factor
Haplotypes
Single Nucleotide Polymorphism
Psychiatry
Central Nervous System
Cytokines

Keywords

  • ADHD
  • association study
  • attention-deficit hyperactivity disorder
  • CNTFR
  • neurotrophic factors
  • neurotrophins
  • NTF3
  • NTRK2

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Association Study of 10 Genes Encoding Neurotrophic Factors and Their Receptors in Adult and Child Attention-Deficit/Hyperactivity Disorder. / Ribasés, Marta; Hervás, Amaia; Ramos-Quiroga, Josep Antoni; Bosch, Rosa; Bielsa, Anna; Gastaminza, Xavier; Fernández-Anguiano, Mònica; Nogueira, Mariana; Gómez-Barros, Núria; Valero, Sergi; Gratacòs, Mònica; Estivill, Xavier P.; Casas, Miquel; Cormand, Bru; Bayés, Mònica.

In: Biological Psychiatry, Vol. 63, No. 10, 15.05.2008, p. 935-945.

Research output: Contribution to journalArticle

Ribasés, M, Hervás, A, Ramos-Quiroga, JA, Bosch, R, Bielsa, A, Gastaminza, X, Fernández-Anguiano, M, Nogueira, M, Gómez-Barros, N, Valero, S, Gratacòs, M, Estivill, XP, Casas, M, Cormand, B & Bayés, M 2008, 'Association Study of 10 Genes Encoding Neurotrophic Factors and Their Receptors in Adult and Child Attention-Deficit/Hyperactivity Disorder', Biological Psychiatry, vol. 63, no. 10, pp. 935-945. https://doi.org/10.1016/j.biopsych.2007.11.004
Ribasés, Marta ; Hervás, Amaia ; Ramos-Quiroga, Josep Antoni ; Bosch, Rosa ; Bielsa, Anna ; Gastaminza, Xavier ; Fernández-Anguiano, Mònica ; Nogueira, Mariana ; Gómez-Barros, Núria ; Valero, Sergi ; Gratacòs, Mònica ; Estivill, Xavier P. ; Casas, Miquel ; Cormand, Bru ; Bayés, Mònica. / Association Study of 10 Genes Encoding Neurotrophic Factors and Their Receptors in Adult and Child Attention-Deficit/Hyperactivity Disorder. In: Biological Psychiatry. 2008 ; Vol. 63, No. 10. pp. 935-945.
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AU - Hervás, Amaia

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AU - Bosch, Rosa

AU - Bielsa, Anna

AU - Gastaminza, Xavier

AU - Fernández-Anguiano, Mònica

AU - Nogueira, Mariana

AU - Gómez-Barros, Núria

AU - Valero, Sergi

AU - Gratacòs, Mònica

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N2 - Background: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder that often persists into adolescence and adulthood and is characterized by inappropriate levels of inattention, hyperactivity, and/or impulsivity. Genetic and environmental factors are believed to be involved in the continuity of the disorder as well as in changes in ADHD symptomatology throughout life. Neurotrophic factors (NTFs), which participate in neuronal survival and synaptic efficiency, are strong candidates to contribute to the neuroplasticity changes that take place in the human central nervous system during childhood, adolescence, and early adulthood and might be involved in the genetic predisposition to ADHD. Methods: We performed a population-based association study in 546 ADHD patients (216 adults and 330 children) and 546 gender-matched unrelated control subjects with 183 single nucleotide polymorphisms covering 10 candidate genes that encode four neurotrophins (NGF, BDNF, NTF3, and NTF4/5), a member of the cytokine family of NTFs (CNTF), and their receptors (NTRK1, NTRK2, NTRK3, NGFR, and CNTFR). Results: The single-marker and haplotype-based analyses provided evidence of association between CNTFR and both adulthood (p = .0077, odds ratio [OR] = 1.38) and childhood ADHD (p = 9.1e-04, OR = 1.40) and also suggested a childhood-specific contribution of NTF3 (p = 3.0e-04, OR = 1.48) and NTRK2 (p = .0084, OR = 1.52) to ADHD. Conclusions: Our data suggest that variations in NTFs might be involved in the genetic susceptibility to ADHD, support the contribution of the CNTFR locus as a predisposition factor for the disorder, and suggest that NTF3 and NTRK2 might be involved in the molecular basis of the age-dependent changes in ADHD symptoms throughout life span.

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