Lea Thaler

Methylation of BDNF in women with bulimic eating syndromes: Associations with childhood abuse and borderline personality disorder

DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to such mental-illness phenotypes as eating disorders. Numerous studies have shown an association between bulimia nervosa (BN) and variations in brain-derived neurotrophic factor (BDNF). BDNF has also been linked to borderline personality disorder (BPD) and to such traits as reward dependence. We examined the extent to which BDNF methylation corresponded to bulimic or normal-eater status, and also to the presence of comorbid borderline personality disorder (BPD) and childhood abuse. Our sample consisted of 64 women with BN and 32 normal-eater (NE) control women. Participants were assessed for eating-disorder symptoms, comorbid psychopathology, and childhood trauma, and then they were required to provide blood samples for methylation analyses. We observed a significant site×group (BN vs. NE) interaction indicating that women with BN showed increases in methylation at specific regions of the BDNF promoter. Furthermore, examining effects of childhood abuse and BPD, we observed significant site×group interactions such that groups composed of individuals with childhood abuse or BPD had particularly high levels of methylation at selected CpG sites. Our findings suggest that BN, especially when co-occurring with childhood abuse or BPD, is associated with a propensity towards elevated methylation at specific BDNF promoter region sites. These findings imply that hypermethylation of the BDNF gene may be related to eating disorder status, developmental stress exposure, and comorbid psychopathology.

Epistatic interactions implicating dopaminergic genes in bulimia nervosa (BN): Relationships to eating- and personality-related psychopathology

We explored the influence of interactions between polymorphisms acting upon postsynaptic receptors (DRD2 TaqA1 rs1800497 and DRD4 7R) and dopamine regulators (COMT rs4680 and DAT1) on the expression of eating symptoms and personality traits in women with bulimia-spectrum eating disorders. We had 269 bulimic women provide blood for genetic assays, and measured eating-disorder symptoms and psychopathological traits using structured interviews and self-report questionnaires. We observed two epistatic interactions on symptom indices: interactions (in predicted directions) of DRD2 by DAT were seen on Body Mass Index (p=.023), and of DRD4 by COMT on self-harming behaviors (p=.014)--with genetic effects that would correspond to reduced dopamine transmission coinciding with more-pathological scores. Our findings suggest that genes acting in the dopamine system interact to influence both eating-related and personality psychopathology, with the result that lower levels of dopamine neuro-transmission correspond to increased psychopathology and body mass in women with bulimia-spectrum disorders. We discuss the implications of our observations.

An examination of the role of autonomous versus controlled motivation in predicting inpatient treatment outcome for anorexia nervosa

OBJECTIVE We explored the effect of autonomous and controlled motivation on outcomes for patients undergoing inpatient treatment for Anorexia Nervosa (AN). METHOD Data on 80 patients with AN were available for the start of treatment, and for 49 at end of treatment. Patients completed measures of autonomous and controlled motivation, eating disorder symptoms and attitudes, and comorbid psychopathology at the start and end of treatment. RESULTS Patients showed significant improvements on eating symptoms and comorbid psychopathology over the course of treatment. Autonomous motivation was a significant predictor of change in severity of eating symptoms and attitudes such that patients with higher pre-treatment levels of autonomous motivation showed larger post-treatment reductions on these indices. No such effects were associated with controlled motivation. DISCUSSION This study highlights a relationship between autonomous motivation and outcome in an inpatient setting.

Epistatic interaction between 5HTTLPR and TPH2 polymorphisms predicts novelty seeking in women with bulimia nervosa spectrum disorders

In individuals with Bulimia Nervosa (BN) and without eating disorders, variations along dimensions such as impulsivity and sensation seeking are influenced by genetic factors that code for serotonin (5-HT) system activity. Low-function alleles of the serotonin transporter polymorphism (5HTTLPR) have been linked to sensation seeking, impulsivity and affective instability in samples of women with BN (Steiger et al., 2005,2007), while the T allele of Tryptophan hydroxylase-2 (TPH2) is associated with impulsivity and lowered harm avoidance in individuals without an eating disorder (Reuter et al., 2007; Stoltenberg et al., 2006). To our knowledge, no study to date has examined psychopathological correlates of TPH2, or the interaction of 5HTTLPR and TPH2 in women with BN. We examined the interaction of 5HTTLPR and a commonly studied SNP of TPH2 ( 703G4T; rs4570625) on psychopathological traits and severity of eating symptoms in a sample of women with BN-spectrum disorders. We hypothesized that individuals carrying a low function allele of 5HTTLPR and the T allele of TPH2 would demonstrate elevations on measures of affective instability, sensation seeking, impulsivity and possibly eating pathology. The present study received ethics board approval from the Douglas Institute. All participants gave informed consent and were compensated. Data were collected as part of a larger study concerning the contribution of selected neurotransmitter-/neuroendocrine-system genes to phenotypic variations in BN. Participants were 273 women, 177 (64.8%) of whom met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for BN purge type, 14 (5.1%) for BN non-purge type, and 82 (30.1%) for Eating Disorder Not Otherwise Specified (EDNOS; variants representing subthreshold BN). Mean age was 25.91 (76.62), while mean BMI (kg/m) was 22.62 (73.84). Almost the entire sample (95.3%) were of Caucasian descent, and 127 women (50.8% of the sample) were using a psychoactive medication when tested (data available from 250 of 273 participants). Participants completed the Eating Attitudes Test (EAT-26) (Garner et al., 1982), the Dimensional Assessment for Personality Pathology (DAPP) (Livesley et al., 1992) that tapped traits in the impulsive-dysregulated spectrum (i.e., stimulus seeking, affective instability, and self-harming behaviors), and the Barratt Impulsiveness Scale (BIS), version 11 (Patton et al., 1995). DNA samples were obtained from whole blood. Genotyping procedures have been described in detail elsewhere (Steiger et al., 2007; Thaler et al., 2012). We applied hierarchical multiple regressions to explore effects of 5HTTLPR [using both biallelic and triallelic models: carriers of

Eating Disorders and Epigenetics

Eating disorders (EDs) are characterized by intense preoccupation with shape and weight and maladaptive eating practices. The complex of symptoms that characterize EDs often arise through the activation of latent genetic potentials by environmental exposures, and epigenetic mechanisms are believed to link environmental exposures to gene expression. This chapter provides an overview of genetic factors acting in the etiology of EDs. It then provides a background to the hypothesis that epigenetic mechanisms link stresses such as obstetric complications and childhood abuse as well as effects of malnutrition to eating disorders (EDs). The chapter then summarizes the emerging body of literature on epigenetics and EDs-mainly studies on DNA methylation in samples of anorexia and bulimia. The available evidence base suggests that an epigenetically informed perspective contributes in valuable ways to the understanding of why people develop EDs.

Epistatic interactions involving DRD2, DRD4, and COMT polymorphisms and risk of substance abuse in women with binge-purge eating disturbances.

Substance abuse is common in individuals with bulimia-spectrum (binge-purge) eating disturbances, a co-occurrence that has been attributed to shared neurobiological substrates--notably alterations in dopaminergic activity. We examined the implications of variations of selected, dopamine-relevant polymorphisms (DRD2 Taq1A, DRD4 7R, and COMT) for risk of substance abuse in women with binge-purge eating syndromes. We genotyped 183 women (66.1% showing full-threshold BN and 33.9% showing sub-syndromic variants), and assessed lifetime presence of alcohol, cannabis, cocaine, and stimulant abuse or dependence using structured interviews. Tests for main and interaction effects of various allele combinations revealed that individuals who carried high function COMT and low-function DRD4 7R alleles (a combination expected to be associated with higher risk) did indeed show more lifetime substance abuse and, specifically, more cannabis abuse. Our findings suggest that a gene combination that, in theory, codes for low levels of dopaminergic neurotransmission coincides with sensitivity to substance abuse in a sample displaying binge-purge eating-disorder variants.

A Tertiary-Care/Primary-Care Partnership Aimed at Improving Care for People with Eating Disorders

We describe the implementation and impact of a province-wide program of knowledge exchange (KE), aimed at developing capacity for the treatment of people with eating disorders (EDs). The program is designed to equip clinicians working in nonspecialized health-care installations with skills to evaluate and treat people with EDs. Trainings were conducted at 21 institutions. The majority of clinicians reported satisfaction with the KE program and indicated that the trainings enhanced their confidence and ability to treat patients with EDs. A subset of clinicians received case supervision with a specialist ED therapist and followed patients with EDs (n = 119). Treated patients showed significant improvements on eating and depressive symptoms, and reported satisfaction with the treatments they received.

Correction to: A Tertiary-Care/Primary-Care Partnership Aimed at Improving Care for People with Eating Disorders

The original version of this article unfortunately contained a mistake in EAT-26 values under “Patients Receiving Treatment for an ED in their Sector” section.