BDNF genetic variants and methylation : effects on cognition in major depressive disorder
Ferrer, Alex (Hospital Universitari de Bellvitge)
Labad, Javier (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Salvat-Pujol, Neus (Hospital Universitari de Bellvitge)
Barrachina, Marta (Hospital Universitari de Bellvitge)
Costas, Javier (Complejo Hospitalario Universitario de Santiago de Compostela)
Urretavizcaya, Mikel (Hospital Universitari de Bellvitge)
De Arriba-Arnau, Aida (Hospital Universitari de Bellvitge)
Crespo, José M. (Hospital Universitari de Bellvitge)
Soriano-Mas, Carles (Universitat Autònoma de Barcelona. Departament de Psicobiologia i de Metodologia de Ciències de la Salut)
Carracedo, Ángel (Fundación Pública Galega de Medicina Xenómica)
Menchón Magriñá, José Manuel (Hospital Universitari de Bellvitge)
Soria, Virginia (Hospital Universitari de Bellvitge)

Fecha:	2019
Resumen:	Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in the BDNF gene were selected for genotype and methylation analysis. The role of interactions between BDNF genetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and two BDNF SNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis that BDNF gene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect of BDNF variations and cognitive function in larger samples.
Ayudas:	Ministerio de Economía y Competitividad PI10/01753 Ministerio de Economía y Competitividad PIE14/00034 Ministerio de Economía y Competitividad PI15/00662 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1247 Ministerio de Economía y Competitividad PT13/0001 Ministerio de Economía y Competitividad CPII16/00019 Ministerio de Economía y Competitividad CPII16/00048
Nota:	Altres ajuts: PT17/0019
Nota:	Altres ajuts: SLT006/17/00012
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Translational psychiatry, Vol. 9, núm. 1 (january 2019) , p. e265, ISSN 2158-3188

DOI: 10.1038/s41398-019-0601-8
PMID: 31636250

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