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Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autism

2010-10Journal article Open access
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dc.contributor.authorCorreia, C.T.
dc.contributor.authorCoutinho, A.M.
dc.contributor.authorSequeira, A.F.
dc.contributor.authorSousa, I.G.
dc.contributor.authorLourenço Venda, L.
dc.contributor.authorAlmeida, J.P.
dc.contributor.authorAbreu, R.L.
dc.contributor.authorLobo, C.
dc.contributor.authorMiguel, T.S.
dc.contributor.authorConroy, J.
dc.contributor.authorCochrane, L.
dc.contributor.authorGallagher, L.
dc.contributor.authorGill, M.
dc.contributor.authorEnnis, S.
dc.contributor.authorOliveira, G.G.
dc.contributor.authorVicente, A.M.
dc.date.accessioned2011-09-20T11:32:12Z
dc.date.available2011-09-20T11:32:12Z
dc.date.issued2010-10
dc.description.abstractThe brain-derived neurotrophic factor (BDNF), a neurotrophin fundamental for brain development and function, has previously been implicated in autism. In this study, the levels of BDNF in platelet-rich plasma were compared between autistic and control children, and the role of two genetic factors that might regulate this neurotrophin and contribute to autism etiology, BDNF and NTRK2, was examined. We found that BDNF levels in autistic children (n = 146) were significantly higher (t = 6.82; P < 0.0001) than in control children (n = 50) and were positively correlated with platelet serotonin distribution (r = 0.22; P = 0.004). Heritability of BDNF was estimated at 30% and therefore candidate genes BDNF and NTRK2 were tested for association with BDNF level distribution in this sample, and with autism in 469 trio families. Genetic association analysis provided no evidence for BDNF or NTRK2 as major determinants of the abnormally increased BDNF levels in autistic children. A significant association with autism was uncovered for six single nucleotide polymorphisms (SNPs) [0.004 (Z((1df)) = 2.85) < P < 0.039 (Z((1df)) = 2.06)] and multiple haplotypes [5 × 10(-4) (χ((3df)) = 17.77) < P < 0.042 (χ((9df)) = 17.450)] in the NTRK2 gene. These results do not withstand correction for multiple comparisons, however, reflect a trend toward association that supports a role of NTRK2 as a susceptibility factor for the disorder. Genetic variation in the BDNF gene had no impact on autism risk. By substantiating the previously observed increase in BDNF levels in autistic children in a larger patient set, and suggesting a genetic association between NTRK2 and autism, this study integrates evidence from multiple levels supporting the hypothesis that alterations in BDNF/tyrosine kinase B (TrkB) signaling contribute to an increased vulnerability to autism.por
dc.identifier.citationGenes Brain Behav. 2010 Oct;9(7):841-8. Epub 2010 Aug 19por
dc.identifier.issn1601-1848
dc.identifier.issndoi: 10.1111/j.1601-183X.2010.00627.x
dc.identifier.urihttp://hdl.handle.net/10400.18/215
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherGenes, Brain and Behaviorpor
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1111/j.1601-183X.2010.00627.x/abstract;jsessionid=AAE6FBCD672CD68780382A3A6FC7A91C.d02t02por
dc.subjectAutismpor
dc.subjectBDNFpor
dc.subjectGenetic associationpor
dc.subjectHeritabilitypor
dc.subjectNTRK2por
dc.subjectPerturbações do Desenvolvimento Infantil e Saúde Mentalpor
dc.titleIncreased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autismpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage848por
oaire.citation.startPage841por
oaire.citation.titleGenes, Brain and Behaviorpor
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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