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

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.

• Authors: M Drabe, M Rullmann, J Luthardt, Y Boettcher, R Regenthal, T Ploetz, G A Becker, M Patt, C Schinke, F T Bergh, F Zientek, A Hilbert, A Bresch, W Fenske, M K Hankir, O Sabri, S Hesse
• Journal: Translational psychiatry (Transl Psychiatry) Vol. 7 Issue 7 Pg. e1167 (07 04 2017) ISSN: 2158-3188 [Electronic] United States
• PMID: 28675387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins

Topics

• Adult
• DNA Methylation
• Epigenesis, Genetic
• Female
• Humans
• Male
• Obesity (genetics)
• Polymorphism, Genetic
• Prefrontal Cortex (metabolism)
• Promoter Regions, Genetic
• Reward
• Serotonin Plasma Membrane Transport Proteins (genetics, metabolism)