The Impact of the Serotonin Transporter Gene Promoter DNA Methylation on Anorexia Nervosa：A Preliminary Longitudinal Study

BackgroudThe serotonin system has been reported to be involved in the pathogenesis of anorexia nervosa (AN). The promoter region of serotonin transporter gene (SLC6A4), also called 5-HTTLPR, responsible for serotonin reuptake, has received much attention, especially 5-HTTLPR methylation, which was associated with abnormal eating behaviors. The study was aimed to explore the association between 5-HTTLPR methylation and AN, as well as its predictive effect on therapeutic response.Methods91 AN patients and 87 healthy controls (HCs) were recruited. Only 30 patients completed the 12-week follow-up. 5-HTTLPR methylation levels and clinical symptoms were assessed at baseline for all participants, at the fourth and the twelfth week for follow-up patients. 5-HTTLPR methylation was measured by MassArray methods and clinical symptoms were mainly evaluated by the EDE-Q6.0 scale. ResultsAN patients had higher methylation at CpG 11, CpG 24.25, CpG 31.32 and CpG_mean than healthy controls (P=0.039, 0.042, 0.018, 0.001). Furthermore, it was the binge/purging subtype that revealed significant hypermethylation at CpG4 and CpG_mean (P=0.027, 0.031). However, it failed to discover significant differences between AN-R and AN-BP groups at all units. Besides, CpG 11 methylation level was positively correlated with EDEQ-6.0 total score in patients (r=0.226, P=0.047). The methylation level of CpG11, CpG26.27.28, CpG31.32, CpG33.34.35.36 and CpG_mean decreased after treatment, but not significantly. 5-HTTLPR methylation was not significantly different between the two groups after treatment.ConclusionsOur study provided preliminary evidence that 5-HTTLPR methylation played vital roles in AN pathogenesis. The characteristic of 5-HTTLPR among untreated AN patients was hypermethylation. However, whether it is the biomarker to distinguish the subtypes and therapeutic response of AN needs further investigation.

Serotonin Transporter Gene Polymorphisms and Maternal Overprotection Regulate Adult Social Expectations on Close Relationships

Humans are evolutionary-driven to adult mating and conceive social expectations on the quality of their affiliations. The genetic susceptibility to adverse environments in critical periods can alter close relationships. The current research investigates how the promoter region of the Serotonin Transporter Gene (5-HTTLPR) and perceived caregiving behavior in childhood could influence the social expectations on close adult relationships. For this purpose, 5-HTTLPR data was collected from the buccal mucosa of 65 Italian individuals (33 males). The participants filled (a) the Parental Bonding Instrument (PBI) to provide the levels of care and overprotection from mother and father, and (b) the Experience in Close Relationships-Revised (ECR-R) to report the social expectations on the intimate relationship assessed in terms of anxiety and avoidance from the partner. An interaction effect between 5-HTTLPR and PBI dimensions on the ECR-R scores was hypothesized. Results confirmed that the interplay between the genetic groups and history of maternal overprotection predicted avoidance experienced in romantic relationships in adulthood. Moreover, both adult anxiety and avoidance felt in an intimate relationship were found to covary as a function of maternal overprotection. The present work proposes further evidence of the genetic and parental mechanisms regulating social expectations involved in close relationships.

The association of the 5-HTTLPR polymorphism and the response to different stressors in healthy males

The experience of stress is related to individual wellbeing and vulnerability to psychopathology. Therefore, understanding the determinants of individual differences in stress reactivity is of great concern from a clinical perspective. The functional promotor polymorphism of the serotonin transporter gene (5-HTTLPR/rs25531) is such a factor, which has been linked to the acute stress response as well as the adverse effect of life stressors. In the present study, we compared the impact of two different stress induction protocols (Maastricht Acute Stress Test and ScanSTRESS) and the respective control conditions on affective ratings, salivary cortisol levels and cognitive performance. To this end, 156 healthy young males were tested and genotyped for the 5-HTTLPR/rs25531 polymorphism. While combined physiological and psychological stress in the MAST led to a greater cortisol increase compared to control conditions as well as the psychosocial ScanSTRESS, subjective stress ratings were highest in the ScanSTRESS condition. Stress induction in general affected working memory capacity but not response inhibition. Subjective stress was also influenced by 5-HTTLPR/rs25531 genotype with the high expression group showing lower stress ratings than lower expression groups. In line with previous research, we identified the low expression variant of the serotonin transporter gene as a risk factor for increased stress reactivity. While some dimensions of the human stress response may be stressor specific, cognitive outcomes such as working memory performance are influenced by stress in general. Different pathways of stress processing and possible underlying mechanisms are discussed.

Inhibitory control mediates the interaction between serotonin transporter gene (5-HTTLPR) and peer victimization on adolescent depressive symptoms

Many efforts have been devoted to investigating the effect of the interaction between the serotonin transporter gene (5-HTTLPR) and environment (G × E) on depression, but they yield mixed results. The inconsistency has suggested that G × E effects may be more complex than originally conceptualized, and further study is warranted. This study explored the association among 5-HTTLPR, peer victimization and depressive symptoms and the underlying mediating role of inhibitory control in this association. A total of 871 Chinese Han adolescents (Mage = 15.32 years, 50.3% girls) participated and provided saliva samples from which the 5-HTTLPR was genotyped. This study found that 5-HTTLPR interacted with peer victimization in predicting depressive symptoms. Adolescents carrying L allele reported more depressive symptoms than SS carriers when exposed to higher level of peer victimization. Furthermore, adolescents’ inhibitory control deficits mediated the association between 5-HTTLPR × peer victimization and depressive symptoms. These findings suggested that one pathway in which G × E may confer vulnerability to depressive symptoms is through disruptions to adolescents’ inhibitory control system.