New-born females show higher stress- and genotype-independent methylation of SLC6A4 than malesReportar como inadecuado

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Borderline Personality Disorder and Emotion Dysregulation

, 2:8

First Online: 15 April 2015Received: 05 August 2014Accepted: 24 March 2015


BackgroundResearch has demonstrated an association between exposure to early life stress and an increased risk of psychiatric disorders in later life, in particular depression. However, the mechanism through which early life stress contributes to disease development remains unclear. Previous studies have reported an association between early life stress and altered methylation of the serotonin transporter gene SLC6A4, a key candidate gene for several psychiatric disorders. These differences in methylation are influenced by sex and genetic variation in the SLC6A4-linked polymorphic region 5-HTTLPR. Furthermore, one study indicated that stress during pregnancy may induce methylation changes in SLC6A4 in the newborn. The present study is the first to investigate whether early life stress during pregnancy impacts on SLC6A4 methylation in newborns, taking into account the influence of genetic variation and sex.

MethodsCord blood was obtained from newborns with high n = 45 or low n = 45 early life stress, defined as maternal stress during pregnancy. The effect on methylation of early life stress, 5-HTTLPR genotype, and sex was assessed at four cytosin-phosphate-guanine dinucleotide CpG sites in the promoter associated CpG island north shore CpG 1 to 4. The epigenetic analyses focused on these CpG sites, since research has shown that CpG island shore methylation has functional consequences.

ResultsSignificant sex-specific methylation was observed, with females displaying higher methylation levels than males p < 0.001. Importantly, this effect was influenced by neither early life stress nor genotype.

ConclusionsThe present data suggest that sex-specific methylation of SLC6A4 is present at birth, and is independent of early life stress and 5-HTTLPR genotype. This may contribute to the sex-specific prevalence of depression.

KeywordsSerotonin transporter SLC6A4 5-HTTLPR Methylation Early life stress Sex Electronic supplementary materialThe online version of this article doi:10.1186-s40479-015-0029-6 contains supplementary material, which is available to authorized users.

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Autor: Helene Dukal - Josef Frank - Maren Lang - Jens Treutlein - Maria Gilles - Isabell AC Wolf - Bertram Krumm - Renaud Massar


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