The Impact Of The Serotonin Transporter Gene Promoter DNA Methylation And Parenting Styles On Anorexia Nervosa

Abstract Purpose: The serotonin system and parenting styles have been reported to be involved in the pathogenesis of anorexia nervosa (AN). The study was aimed to explore the effect of the methylation of the promoter region of serotonin transporter gene (SLC6A4), also called 5-HTTLPR, parenting styles as well as their interaction on AN.Methods: 91 AN patients (ANs) and 87 healthy controls (HCs) were recruited, from whom 41 ANs and 40 HCs completed the environmental assessment. 5-HTTLPR methylation levels, clinical symptoms and environmental factors were assessed at baseline for all participants. 5-HTTLPR methylation was measured by MassArray methods and clinical symptoms were mainly evaluated by the EDE-Q6.0 scale. Environmental assessment is the parenting attitudes and behaviors used by the EMBU scale.Results: ANs had higher methylation at CpG 11, CpG 24.25, CpG 31.32 and CpG_mean than HCs (P=0.039, 0.042, 0.018, 0.001). Furthermore, it was the binge/purging subtype that revealed significant hypermethylation at CpG 24.25 and CpG_mean (P=0.027, 0.031). Both CpG11 methylation level and the parenting styles of refusal denial, overprotection for father were both positively correlated the EDEQ-6.0 scores in ANs (P=0.047, 0.018). Besides, their interaction analysis found, it was the overprotection, not the refusal denial for father that significantly associated with EDEQ-6.0 scores in ANs (P=0.030).Conclusions: Our study provided preliminary evidence that 5-HTTLPR DNA methylation at CpG11 and parenting styles of refusal denial, overprotection for father played vital roles in AN pathogenesis. Their interaction analysis indicated it was father’s overprotection that significantly associated with the clinical symptoms in ANs.