A systematic review and secondary data analysis of the interactions between the serotonin transporter 5-HTTLPR polymorphism and environmental and psychological factors in eating disorders

Abstract

Objectives To summarize and synthesize the growing gene x environment (GxE) research investigating the promoter region of the serotonin transporter gene (5-HTTLPR) in the eating disorders (ED) field, and overcome the common limitation of low sample size, by undertaking a systematic review followed by a secondary data meta-analysis of studies identified by the review. Method A systematic review of articles using PsycINFO, PubMed, and EMBASE was undertaken to identify studies investigating the interaction between 5-HTTLPR and an environmental or psychological factor, with an ED-related outcome variable. Seven studies were identified by the systematic review, with complete data sets of five community (n=1750, 64.5% female) and two clinical (n=426, 100% female) samples combined to perform four secondary-data analyses: 5-HTTLPR x Traumatic Life Events to predict ED status (n=909), 5-HTTLPR x Sexual and Physical Abuse to predict bulimic symptoms (n=1097), 5-HTTLPR x Depression to predict bulimic symptoms (n=1256), and 5-HTTLPR x Impulsiveness to predict disordered eating (n=1149). Results Under a multiplicative model, the low function (s) allele of 5-HTTLPR interacted with traumatic life events and experiencing both sexual and physical abuse (but not only one) to predict increased likelihood of an ED and bulimic symptoms, respectively. However, under an additive model there was also an interaction between sexual and physical abuse considered independently and 5-HTTLPR, and no interaction with traumatic life events. No other GxE interactions were significant. Conclusion Early promising results should be followed-up with continued cross-institutional collaboration in order to achieve the large sample sizes necessary for genetic research.

Catechol‐O‐Methyltransferase (COMT) Val158Met Polymorphism and Eating Disorders: Data From a New Biobank and Meta‐Analysis of Previously Published Studies

“…The fact that less studies investigated COMT polymorphisms in BN, compared with AN, is consistent with the more limited neurobiological characterization of BN and with a less homogeneous description of its neuropsychological functioning (Degortes, Tenconi, Santonastaso, & Favaro, ; Van den Eynde et al, ). Moreover, the absence of an association between COMT Val158Met genotype and ED mirrors similar results for the serotonin transporter 5‐HTTLPR polymorphism, another monoamine modulating single polymorphism as previously reported (Rozenblat et al, ; Solmi et al, ).…”

Relationships Between Self‐Reported and Observed Parenting Behaviour, Adolescent Disordered Eating Attitudes and Behaviours, and the 5‐HTTLPR Polymorphism: Data From the Australian Temperament Project

“…In the present study, data were not available to examine the triallelic model, which may yet have resulted in identification of a GxE interaction in the present sample. Furthermore, the sample size, particularly in Study 2, was relatively underpowered for genetic association studies (although it was above the mean N = 288 of GxE studies in the ED field; Rozenblat et al , ). Conversely, the sample in Study 1 constitutes the third largest investigation of its kind in the field (following Akkermann et al , , N = 765, and the combined‐samples analyses in Rozenblat et al , , N > 1000).…”

“…The s‐allele has been implicated in changes in appetite, mood, and the stress‐response system (Gotlib, Joormann, Minor, & Hallmayer, ; Leibowitz & Alexander, ; Ruhé, Mason, & Schene, ) and thus is of direct relevance to ED aetiology. As such, most GxE investigations in eating pathology have focussed on 5‐HTTLPR , with a recent meta‐analysis finding significant interactions between 5‐HTTLPR and traumatic life events, as well as sexual and physical abuse, in predicting EDs and bulimia nervosa (BN), respectively (Rozenblat et al , ). However, no study in the ED field has examined GxE ‘risk’ from a plasticity perspective.…”

“…For example, individuals exposed to 'risky' environments may develop ED symptoms only if they also carry certain 'risky' psychological or genetic factors (Stice, Marti, & Durant, 2011). In particular, following a lack of findings of direct genetic effects (Root et al, 2011), a growing area of ED research involves examining how individual genetic differences may moderate the impact of certain environmental variables on ED symptoms (Rozenblat et al, 2017).…”

Challenges in diagnosis and treatment of comorbid eating disorders and mood disorders

“…Having one or two short alleles in the serotonin-transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene has been studied in relationship to rejection sensitivity, 23 depression, 24 bipolar disorder 25 and eating disorders. 26 The short allele of the serotonintransporter gene is associated with increased amygdala reactivity in response to perceived threat coupled with compromised prefrontal cortex connections that typically downregulate amygdala activity. 27,28 This alteration in amygdala circuits has been associated with an anxious phenotype referred to as "neuroticism."…”