Dopamine-system genes, childhood abuse, and clinical manifestations in women with Bulimia-Spectrum Disorders.

OBJECTIVE: We explored interaction effects involving polymorphisms of targeted dopamine system genes and selected forms of childhood abuse (sexual, physical and emotional) acting upon severity of binge-eating and psychopathological symptoms in women with Bulimia-Spectrum Disorders (BSDs). METHODS: Women diagnosed with a BSD (n = 216) were assessed for childhood traumata, eating-disorder (ED) symptoms, and selected psychopathological features (sensation seeking, impulsivity, compulsivity and affective instability), and then provided blood samples for genotyping of main polymorphisms of dopamine-2 receptor (DRD2), dopamine transporter (DAT1) and catechol o-methyltransferase (COMT) genes. RESULTS: Sensation Seeking was elevated in carriers of the low-function allele of the DRD2 Taq1A polymorphism who also reported childhood sexual abuse, relative to that in individuals showing other combinations of alleles and abuse exposures. In addition, carriers of a low-function allele of COMT scored higher on compulsivity, lower on impulsivity, and marginally lower on frequency of binge-eating than did individuals in whom the allele was absent. DISCUSSION: Our results suggest that genes acting within the dopamine system may contribute, either directly or indirectly (i.e., in interaction with traumatic childhood experiences), to variations in the presentation of comorbid traits and, possibly, of bulimic symptoms.

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.

Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: associations with clinical symptoms.

INTRODUCTION: Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. METHOD: Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. RESULTS: Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. CONCLUSIONS: Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations.

Autonomous motivation: a predictor of treatment outcome in bulimia-spectrum eating disorders.

UNLABELLED: Individuals with eating disorders are said to be highly ambivalent towards change and thus have difficulty maintaining a commitment to, and motivation for, treatment. Self-Determination Theory postulates that autonomous motivation for therapy exists when individuals view their participation as freely chosen. OBJECTIVE: The present study was designed to ascertain whether or not autonomous motivation was associated with treatment response in individuals with bulimia-spectrum eating disorders (BSED). METHOD: One hundred and fifty-five women with DSM-IV-TR BSED participated in multimodal group therapy and completed measures to assess motivation, eating and comorbid symptoms. RESULTS: Hierarchical multiple regression analyses demonstrated that higher levels of autonomous motivation at pretreatment predicted lower post-treatment scores on measures of eating preoccupations (shape, weight and eating concerns), binge eating, anxiety/depression, relationship to self and others and impulsivity. DISCUSSION: These results indicate that autonomous motivation may be an important predictor of outcome following treatment for BSED.

Childhood emotional abuse and eating symptoms in bulimic disorders: an examination of possible mediating variables.

OBJECTIVE: We sought to estimate prevalences of childhood emotional abuse (CEA) in bulimic and normal-eater control groups, and to replicate previous findings linking CEA to severity of eating symptoms in BN. We also examined potential mediators of the link between CEA and disordered eating. METHOD: Women diagnosed with a bulimic disorder (n = 176) and normal-eater women (n = 139) were assessed for childhood traumata, eating-disorder (ED) symptoms and psychopathological characteristics (ineffectiveness, perfectionism, depression, and affective instability) thought to be potential mediators of interest. RESULTS: CEA was more prevalent in the bulimic than in the nonbulimic group, and predicted severity of some eating-symptom indices. Ineffectiveness and affective instability both mediated relationships between CEA and selected ED symptoms. DISCUSSION: We found CEA to predict eating pathology through mediating effects of ineffectiveness and affective instability. CEA might influence severity of ED symptoms by impacting an individual's self-esteem and capacity for affect regulation.

Interaction of the BcII glucocorticoid receptor polymorphism and childhood abuse in Bulimia Nervosa (BN): relationship to BN and to associated trait manifestations.

We recently documented a gene-environment interaction suggesting that individuals with Bulimia Nervosa (BN) differed from normal eaters as to the combined presence of the low-function allele of the glucocorticoid receptor polymorphism, BcII, and childhood abuse. The present study examined the extent to which any such interaction effect may have been attributable to behavioral impulsivity, sensation seeking, affective instability or depression. We had 174 bulimic and 130 nonbulimic women provide blood for genetic assays, and measured psychopathological traits and childhood abuse using structured interviews and self-report questionnaires. As expected, we observed a significant BcII × abuse interaction indicating genetic and environmental susceptibilities to co-occur significantly more often in bulimic than in nonbulimic individuals. The BcII × abuse interaction was attenuated when levels of depression were accounted for, but was surprisingly unaffected by controls for motoric impulsivity, sensation seeking or affective instability. Our findings suggest that stress-induced alterations in glucocorticoid sensitivity contribute to BN and depressive disturbances--without being associated with the behavioral/affective dysregulation seen in many BN sufferers. We discuss theoretical and clinical implications of these observations.