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• W2138320652 endingPage "e402" @default.
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• W2138320652 abstract "The serotonin transporter (SERT) gene-linked polymorphic region (5-HTTLPR) has been implicated in moderating the link between life stress and depression. However, respective molecular pathways of gene-environment (GxE) interaction are largely unknown. Sustained alterations in SERT gene expression profiles, possibly mediated by epigenetic modifications, are a frequent correlate of depression and may thus constitute a putative mediator of GxE interaction. Here, we aimed to investigate joint effects of 5-HTTLPR and self-reported environmental adversity throughout the lifespan (prenatal, early and recent stress/trauma) on in vivo SERT mRNA expression in peripheral blood cells. To further evaluate whether environmentally induced changes in SERT expression are mediated by epigenetic modifications, we analyzed 83 CpG sites within a 799-bp promoter-associated CpG island of the SERT gene using the highly sensitive method of bisulfite pyrosequencing. Participants were 133 healthy young adults. Our findings show that both the 5-HTTLPR S allele and maternal prenatal stress/child maltreatment are associated with reduced in vivo SERT mRNA expression in an additive manner. Remarkably, individuals carrying both the genetic and the environmental risk factors exhibited 32.8% (prenatal stress) and 56.3% (child maltreatment) lower SERT mRNA levels compared with those without any risk factor. Our data further indicated that changes in SERT mRNA levels were unlikely to be mediated by DNA methylation profiles within the SERT CpG island. It is thus conceivable that the persistent changes in SERT expression may in turn relate to altered serotonergic functioning and possibly convey differential disease vulnerability associated with 5-HTTLPR and early adversity." @default.
• W2138320652 created "2016-06-24" @default.
• W2138320652 creator A5032855523 @default.
• W2138320652 creator A5043730479 @default.
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• W2138320652 creator A5050846056 @default.
• W2138320652 creator A5081975383 @default.
• W2138320652 creator A5083695665 @default.
• W2138320652 date "2014-06-17" @default.
• W2138320652 modified "2023-10-17" @default.
• W2138320652 title "Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles" @default.
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• W2138320652 doi "https://doi.org/10.1038/tp.2014.37" @default.
• W2138320652 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4080318" @default.
• W2138320652 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24937096" @default.
• W2138320652 hasPublicationYear "2014" @default.
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