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Variation at NRG1 genotype related to modulation of small-world properties of the functional cortical network

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Abstract

Functional brain networks possess significant small-world (SW) properties. Genetic variation relevant to both inhibitory and excitatory transmission may contribute to modulate these properties. In healthy controls, genotypic variation in Neuregulin 1 (NRG1) related to the risk of psychosis (risk alleles) would contribute to functional SW modulation of the cortical network. Electroencephalographic activity during an odd-ball task was recorded in 144 healthy controls. Then, small-worldness (SWn) was calculated in five frequency bands (i.e., theta, alpha, beta1, beta2 and gamma) for baseline (from −300 to the stimulus onset) and response (150–450 ms post-target stimulus) windows. The SWn modulation was defined as the difference in SWn between both windows. Association between SWn modulation and carrying the risk allele for three single nucleotide polymorphisms (SNP) of NRG1 (i.e., rs6468119, rs6994992 and rs7005606) was assessed. A significant association between three SNPs of NRG1 and the SWn modulation was found, specifically: NRG1 rs6468119 in alpha and beta1 bands; NRG1 rs6994992 in theta band; and NRG1 rs7005606 in theta and beta1 bands. Genetic variation at NRG1 may influence functional brain connectivity through the modulation of SWn properties of the cortical network.

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Acknowledgments

The study we present has been supported by grants GRS A/14/932 and GRS A/15/1134 from the Gerencia Regional de Salud de Castilla y León (Spain), PI15/00299 from the Carlos III Institute of the Ministry of Health (Spain) and a predoctoral fellowship grant to Alba Lubeiro from Consejería de Educación- Junta de Castilla y León (Spain) and European Social Fund.

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Authors and Affiliations

  1. Psychiatry Department, Faculty of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005, Valladolid, Spain

    Alba Lubeiro, Oscar Martín & Vicente Molina

  2. Biomedical Engineering Group, E.T.S. Ingenieros de Telecomunicación, University of Valladolid, Paseo de Belén, 15, 47011, Valladolid, Spain

    Javier Gomez-Pilar, Jesús Poza & Roberto Hornero

  3. Neurotek, Neurosciences Department, Achucarro Basque Center for Neurosciences, University of the Basque Country, 48170, Zamudio, Vizcaya, Spain

    Aitor Palomino

  4. Psychiatry Department, Hospital Universitario de Álava, Jose Atxotegi, s/n, 01009, Vitoria-Gasteiz, Álava, Spain

    Myriam Fernández & Ana González-Pinto

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  1. Alba Lubeiro
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  2. Javier Gomez-Pilar
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  3. Oscar Martín
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  9. Vicente Molina
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Correspondence to Vicente Molina.

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All participants provided written informed consent to participate in the study. It was approved by the ethical committee of the three hospitals involved in the study (University Hospitals of Alava, Salamanca and Valladolid) according to the Code of Ethics of the World Medical Association (Helsinki Declaration of 1975, as revised in 2008).

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Lubeiro, A., Gomez-Pilar, J., Martín, O. et al. Variation at NRG1 genotype related to modulation of small-world properties of the functional cortical network. Eur Arch Psychiatry Clin Neurosci 267, 25–32 (2017). https://doi.org/10.1007/s00406-015-0659-0

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  • DOI: https://doi.org/10.1007/s00406-015-0659-0

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