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  Serotonin transporter gene promoter methylation status correlates with in vivo prefrontal 5-HTT availability and reward function in human obesity

Drabe, M., Rullmann, M., Luthardt, J., Boettcher, Y., Regenthal, R., Ploetz, T., et al. (2017). Serotonin transporter gene promoter methylation status correlates with in vivo prefrontal 5-HTT availability and reward function in human obesity. Translational Psychiatry, 7(7): e1167. doi:10.1038/tp.2017.133.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-E5DA-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-B735-3
Genre: Journal Article

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 Creators:
Drabe, M.1, Author
Rullmann, Michael2, Author              
Luthardt , J.1, Author
Boettcher, Y.1, Author
Regenthal, R.1, Author
Ploetz, T.1, Author
Becker, G. A.1, Author
Patt, M.1, Author
Schinke, C .1, Author
Bergh, F. T.1, Author
Zientek, F.1, Author
Hilbert, A .1, Author
Bresch, A .1, Author
Fenske, W.1, Author
Hankir, M. K.1, Author
Sabri, O.1, Author
Hesse, S.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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Free keywords: Clinical genetics; Epigenetics and behaviour
 Abstract: A polymorphism in the promoter region of the human serotonin transporter (5-HTT)-coding SLC6A4 gene (5-HTTLPR) has been implicated in moderating susceptibility to stress-related psychopathology and to possess regulatory functions on human in vivo 5-HTT availability. However, data on a direct relation between 5-HTTLPR and in vivo 5-HTT availability have been inconsistent. Additional factors such as epigenetic modifications of 5-HTTLPR might contribute to this association. This is of particular interest in the context of obesity, as an association with 5-HTTLPR hypermethylation has previously been reported. Here, we tested the hypothesis that methylation rates of 14 cytosine–phosphate–guanine (CpG) 5-HTTLPR loci, in vivo central 5-HTT availability as measured with [11C]DASB positron emission tomography (PET) and body mass index (BMI) are related in a group of 30 obese (age: 36±10 years, BMI>35 kg/m2) and 14 normal-weight controls (age 36±7 years, BMI<25 kg/m2). No significant association between 5-HTTLPR methylation and BMI overall was found. However, site-specific elevations in 5-HTTLPR methylation rates were significantly associated with lower 5-HTT availability in regions of the prefrontal cortex (PFC) specifically within the obese group when analyzed in isolation. This association was independent of functional 5-HTTLPR allelic variation. In addition, negative correlative data showed that CpG10-associated 5-HTT availability determines levels of reward sensitivity in obesity. Together, our findings suggest that epigenetic mechanisms rather than 5-HTTLPR alone influence in vivo 5-HTT availability, predominantly in regions having a critical role in reward processing, and this might have an impact on the progression of the obese phenotype.

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Language(s): eng - English
 Dates: 2017-04-082016-11-282017-05-092017-07-04
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/tp.2017.133
PMID: 28675387
PMC: PMC5538116
 Degree: -

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Project name : -
Grant ID : 01E01501
Funding program : -
Funding organization : IFB Adiposity Diseases, German Federal Ministry of Education and Research (BMBF)

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Title: Translational Psychiatry
  Abbreviation : Transl Psychiatry
Source Genre: Journal
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Publ. Info: Nature Pub. Group
Pages: - Volume / Issue: 7 (7) Sequence Number: e1167 Start / End Page: - Identifier: ISSN: 2158-3188
CoNE: https://pure.mpg.de/cone/journals/resource/2158-3188