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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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.)

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., (Copyright © 2011 Wiley Periodicals, Inc.)

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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This study evaluated the hypothesis that traumatic stress can increase risk of bulimia nervosa (BN) in individuals who are genetically disposed towards lower modulation of physiological stress reactions. We explored the extent to which childhood abuse (physical or sexual), variants of a main glucocorticoid receptor (GR) polymorphism (Bcl1), or their interaction, differentiated women with and without BN. Women seeking treatment for BN (N=129) and non-eating-disordered comparison women (N=98) provided blood samples for assays of the Bcl1 polymorphism, and completed structured interviews assessing eating symptoms, psychiatric symptoms and childhood abuse. Compared to normal-eaters, bulimic women were significantly more likely to carry the low-function Bcl1 C allele (CC or CG genotypes), to report a history of childhood abuse and, more importantly, to be positive for both factors. We interpret our findings as indicating that traumatic stress, when impacting individuals disposed to lower GR modulation, can be etiological for BN., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the effects of acute alcohol intoxication on eating-related urges among women with bulimia nervosa (BN)., Method: Participants included women with BN or normal-weight eating disorder NOS with regular binge/purge symptoms (N = 13), and normal-eater control women (N = 17). Tested individually, the women reported on their mood state as well as on urges to binge eat and engage in various compensatory behaviors, prior to consuming alcohol, and again at 60 and 180 min following the consumption of 1.0 ml kg(-1) alcohol., Results: Both groups reported feeling less clearheaded after drinking, as well as initial subjective mood stimulation followed by subsequent mood lowering. In addition, BN participants reported reductions in their urges to binge eat, exercise compulsively, and restrict food intake following alcohol consumption-the urge to purge was not significantly affected., Discussion: Among women with BN, alcohol consumption appeared to reduce select eating-related urges with concomitant reductions in attention or concentration., (Copyright © 2010 Wiley Periodicals, Inc.)

Background: Previous research has shown that many people experience a temporary worsening of mood following acute tryptophan depletion (ATD) and that concurrent use of serotonergic medications may influence such mood responses. We investigated mood and other consequences of ATD in women with bulimia nervosa who were or were not using concurrent serotonergic medications compared with women without bulimia., Methods: Women self-referred for treatment of bulimia who were either not currently using psychoactive medications (n = 26) or who were using serotonin reuptake inhibitor medications exclusively (n = 13), as well as medication-free normal-eater control women (n = 25) completed interviews and questionnaires assessing eating and comorbid psychopathology and then participated in an ATD procedure involving balanced and tryptophan-depleted conditions., Results: In the tryptophan-depleted condition, the groups displayed similar and significant decrements in plasma tryptophan levels and mood. Women with bulimia who were using serotonin reuptake inhibitors, but not the other groups, also reported an increased urge to binge eat in the tryptophan-depleted condition., Limitations: Application of medication in participants with bulimia was not random., Conclusion: Acute reductions in serotonin availability produced similar mood-reducing effects in bulimic and nonbulimic women. To the extent that ATD affected subjective experiences pertinent to eating (i.e., urge to binge eat), such effects appeared to depend upon ATD-induced competition with the therapeutic effects of serotonergic medications.

Objective: To investigate behavior-outcome expectancies relating to thinness, dietary restriction, eating, and alcohol consumption in women with bulimia nervosa (BN)., Method: Women with BN (N = 29), women with BN and a co-morbid lifetime alcohol use disorder (AUD; N = 18), and control women (N = 24), completed interviews and questionnaires assessing eating- and alcohol-related symptoms, as well as questionnaires measuring expectancies relating to thinness, dietary restriction, eating, and alcohol consumption., Results: Compared with the control group, both bulimic groups reported greater positive expectancies relating to thinness, dietary restriction and eating; expectancy endorsements were also predictive of the severity of eating-related symptoms. Compared with the other groups, the bulimic group with comorbid lifetime AUD had elevated positive alcohol-related expectancies, and alcohol expectancy endorsements predicted severity of alcohol-related symptoms., Discussion: Women with BN endorsed more positive expectancies relating to thinness, dietary restriction, and eating, whereas women with BN and a lifetime comorbid AUD endorsed more positive alcohol expectancies. The results are consistent with expectancy theory in that positive expectancy endorsements were associated with symptom severity in a syndrome-specific manner. Expectancies related to thinness, dietary restriction, eating, and alcohol consumption in women with BN., ((c) 2008 by Wiley Periodicals, Inc.)

Background: We tested the hypothesis that individuals carrying low-function alleles of the serotonin transporter (5-HTTLPR) and 5-HT(2A) receptor gene (-1438G/A) promoter polymorphisms would show relatively poor treatment responses on indices of bulimic and concurrent symptoms., Method: Participants included 111 women with bulimia-spectrum eating disorders (DSM-IV-TR criteria), 98 of whom were followed through 4- to 8-month spans of specialized multimodal treatment to enable examination of relationships between genotypes and prospective changes in eating and general psychiatric symptoms. Given a hierarchically structured dataset and a desire to control for effects of variations in adjunctive pharmacotherapy, individual therapy, group therapy, or day treatment, we used multilevel modeling techniques. The study was conducted between October 2001 and May 2007., Results: After effects of treatments were removed, 5-HTTLPR low-function allele carriers showed smaller treatment reductions in binge eating (p < .01) and in anxiety and depression (p < .05), whereas low-function -1438G/A G carriers showed smaller reductions in binge eating (p < .01) and impulsivity (p < .05)., Conclusions: This study documents an expected association between poorer bulimia-treatment response and low-function alleles of 5-HTTLPR and -1438G/A--and suggests that such effects cannot be attributed to mediating influences of medication or psychotherapy responsiveness alone. A better understanding of hereditary, serotonin-mediated factors affecting bulimic individuals' progress during therapy may facilitate the development of more effective treatments., (Copyright 2008 Physicians Postgraduate Press, Inc.)

Objective: Individuals with bulimia nervosa have been shown to display heterogeneous profiles of comorbid psychiatric disturbance, possibly due to varying degrees of genetic and environmental vulnerability. Using information about comorbid psychiatric disturbances, we developed an empirically based classification of individuals with bulimia-spectrum disorders, and then explored whether or not the resulting phenotypes corresponded to variations in the serotonin transporter promoter polymorphism (5-HTTLPR) and exposure to childhood abuse., Method: Eighty-nine women aged 17 to 49 years with DSM-IV bulimia-spectrum disorders completed questionnaires assessing eating and general psychopathologic symptoms, participated in interviews assessing Axis I disorders and childhood abuse, and provided blood samples for genotyping. Data on lifetime Axis I disorders were analyzed using latent class analysis, and resulting classes were compared on eating and psychopathologic symptoms, 5-HTTLPR genotype, and childhood abuse. The study was conducted from June 2002 to October 2006., Results: The analysis yielded a model with 2 classes: a first class labeled low comorbidity (N = 59, 66%), characterized by a high likelihood of major depressive disorder, and another class labeled high comorbidity (N = 30, 34%), characterized by a high likelihood of major depressive disorder, anxiety disorder, and substance-use disorders. The high-comorbidity class displayed significantly higher dieting preoccupations and conduct problems, and showed a greater likelihood of carrying the 5-HTTLPR S allele and of childhood abuse than did the low-comorbidity class., Conclusions: The present results are consistent with previous findings identifying a subgroup of individuals with bulimia characterized by high psychiatric comorbidity and suggest that the 5-HTTLPR polymorphism and childhood trauma may both be pertinent to explaining the presence of greater psychiatric comorbidity in bulimia-spectrum disorders.

We recently reported that, among bulimic women, previously abused carriers of the 5HTTLPR S allele showed special propensities towards novelty seeking (implying recklessness or impulsivity) and interpersonal insecurity. We subsequently re-analyzed our data, to examine the bearing of the 5HTTLPR polymorphism and prior sexual or physical maltreatment upon validated, higher-order personality-traits. Ninety women with bulimic syndromes were genotyped for 5HTTLPR "short" (S) and "long" (L(G) and L(A)) alleles, and then assessed for eating symptoms, history of sexual or physical abuse, and the higher-order personality traits Emotional Dysregulation, Dissocial Behavior, Inhibition, and Compulsivity. With a classification based on a biallelic model of 5HTTLPR (i.e., presence or absence of at least one S-allele copy), multiple regression indicated a significant proportion of variance in Dissocial Behavior to be explained by an abuse x genotype interaction-greater psychopathology occurring in abused S-allele carriers. A parallel analysis applying a triallelic model of 5HTTLPR (i.e., presence or absence of at least one copy of presumably low-function S or L(G) alleles) produced a similar pattern, but no statistically significant effect. The finding that bulimic 5HTTLPR S-allele carriers who are previously abused display elevations on Dissocial Behavior corroborates previous observations concerning phenomenological correlates of traumatic stress in 5HTTLPR S allele carriers. (c) 2007 Wiley-Liss, Inc.

Objectives: To review the main phenomenological variants observed among bulimia spectrum syndromes and the factors believed to act etiologically for them and also to generate an etiologic model that accommodates known heterogeneities within the population suffering bulimic syndromes., Method: Defining bulimic syndromes broadly, we address threshold and subthreshold forms of bulimia nervosa (BN) and also the provisional or newly proposed diagnoses of binge eating disorder (BED) and purging disorder (PD). We review evidence bearing on the validity of these diagnostic entities and on the place of sociocultural, family-developmental, neurobiological, and genetic factors in a multidimensional etiologic model for these classifications., Results: Available data validate certain bulimic phenotypes and subphenotypes that are characterized by such traits as impulsivity or affective instability. Findings associate subphenotypic, or trait-based, variations with putative endophenotypes, such as reduced serotonin transporter activity, and with candidate genotypes affecting the serotonin system; the data also indicate intriguing correspondences between gene environment interactions and subphenotypic variations along such dimensions as novelty seeking., Conclusions: Bulimic syndromes sometimes reflect a primary disruption of controls over mood, impulses, and appetite in individuals showing marked psychopathology; at other times, they reflect a more circumscribed erosion of appetitive controls in relatively intact individuals, following prolonged dieting. We argue that dimensional perspectives involving careful attention to comorbid personality traits and symptoms are needed to accommodate existing heterogeneities within the population suffering from bulimia and to characterize the etiologic roles of familial-developmental, neurobiological, and genetic variables (and of interactions among these variables) in bulimic syndromes.

Objective: Impulsivity is generally believed to be more characteristic of individuals with bulimic than with restrictive eating disorders (EDs). However, studies have not exhaustively explored the association between EDs and various component dimensions of the impulsivity construct., Method: We conducted a multidimensional assessment of impulsivity in 84 women with bulimia nervosa (BN), 37 with anorexia nervosa (AN: 19 restricters and 18 bingers-purgers), and 61 normal-control participants. To assess multiple components of impulsivity, participants completed a battery of self-report questionnaires and a performance test., Results: Compared with normal-control participants, all ED groups showed attentional problems. However, only women suffering BN or AN-binge purge subtype showed elevations on motoric forms of impulsivity, whereas women with BN were the only group to report tendencies toward reckless behavior., Conclusion: These findings suggest that binge-eating behavior coincides with problems of response inhibition, whereas a risk-taking attitude may be a unique characteristic of individuals with BN., ((c) 2006 by Wiley Periodicals, Inc.)

Reduced brain serotonin (5-hydroxytryptamine: 5-HT) transporter activity has been associated with susceptibility to various forms of psychopathology, including bulimia nervosa (BN) and related syndromes characterized by appetitive or behavioural dysregulation. We applied density (Bmax) of platelet [3H-]paroxetine binding as a proxy for central 5-HT reuptake activity in two groups of women (33 with BN-spectrum disorders and 19 with no apparent eating or psychiatric disorders), most of these individuals' mothers (31 and 18, respectively), and a small sampling of their sisters (seven and eight, respectively). Hierarchical linear modeling techniques were used to account for nesting of individuals within families and diagnostic groupings. Bulimic probands, their mothers, and their sisters all displayed significantly lower density (Bmax) of platelet-paroxetine binding than did 'control' probands, mothers, or sisters-even when relatives showing apparent eating or psychiatric disturbances were excluded. In addition, in bulimic probands and mothers, significant within-family correlations were obtained on Bmax. These findings imply a heritable trait (or endophenotype), linked to 5-HT activity, and carried by BN sufferers and their first-degree relatives (even when asymptomatic). We propose that, under conducive circumstances, such a trait may increase risk of binge-eating behavior, or associated symptoms of affective or behavioral dysregulation.

Separate lines of research suggest that the functional alterations in the serotonin (5-HT) 2A receptor are associated with 5-HT tone, behavioral impulsiveness, and bulimia nervosa (BN). We explored the effect of allelic variations within the 5-HT2A receptor gene promoter polymorphism -1438G/A on trait impulsiveness and serotonin function in women with BN. Participants included women with BN having the A allele (i.e., AA homozygotes and AG heterozygotes, BNA+, N = 21); women with BN but without the A allele (i.e., GG homozygotes, BNGG, N = 12), and normal eater control women having the A allele (NEA+, N = 19) or without the A allele (NEGG; N = 9). The women were assessed for psychopathological tendencies and eating disorder symptoms, and provided blood samples for measurement of serial prolactin responses following oral administration of the post-synaptic partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP). The BNGG group had higher scores than the other groups on self-report measures of non-planning and overall impulsiveness and had blunted prolactin response following m-CPP. The bulimic groups did not differ from each other on current eating symptoms or on frequencies of other Axis I mental disorders. Findings indicate that women with BN who are GG homozygotes on the -1438G/A promoter polymorphism are characterized by increased impulsiveness and lower sensitivity to post-synaptic serotonin activation. These findings implicate the GG genotype in the co-aggregation of impulsive behaviors and alterations of post-synaptic 5-HT functioning in women with BN., ((c) 2005 Wiley-Liss, Inc.)

Abstract: 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 0.5mg 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. [Copyright &y& Elsevier]

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Reduced brain serotonin (5-hydroxytryptamine: 5-HT) transporter activity has been associated with susceptibility to various forms of psychopathology, including bulimia nervosa (BN) and related syndromes characterized by appetitive or behavioural dysregulation. We applied density (Bmax) of platelet [3H-]paroxetine binding as a proxy for central 5-HT reuptake activity in two groups of women (33 with BN-spectrum disorders and 19 with no apparent eating or psychiatric disorders), most of these individuals' mothers (31 and 18, respectively), and a small sampling of their sisters (seven and eight, respectively). Hierarchical linear modeling techniques were used to account for nesting of individuals within families and diagnostic groupings. Bulimic probands, their mothers, and their sisters all displayed significantly lower density (Bmax) of platelet-paroxetine binding than did ‘control’ probands, mothers, or sisters—even when relatives showing apparent eating or psychiatric disturbances were excluded. In addition, in bulimic probands and mothers, significant within-family correlations were obtained on Bmax. These findings imply a heritable trait (or endophenotype), linked to 5-HT activity, and carried by BN sufferers and their first-degree relatives (even when asymptomatic). We propose that, under conducive circumstances, such a trait may increase risk of binge-eating behavior, or associated symptoms of affective or behavioral dysregulation.Neuropsychopharmacology (2006) 31, 1785–1792. doi:10.1038/sj.npp.1301011; published online 11 January 2006 [ABSTRACT FROM AUTHOR]

Findings show brain serotonin (5-hydroxytryptamine (5-HT)) activity to be altered in individuals who have had bulimia nervosa (BN), even after substantial remission of symptoms. Such findings could reflect persistent sequelae due to BN, or a vulnerability 'trait' that exists independently of active eating-disorder manifestations. We compared women with full-blown BN (BN; n = 22), BN in remission (BN-R; n = 11), and no eating or psychiatric disturbances (n = 22) on measures of platelet [³H]paroxetine binding, eating symptoms and psychopathology. The BN-R group showed normal-range scores on eating and psychopathological symptoms, but reductions in density (Bmax) of binding sites for paroxetine similar to those obtained in the actively ill women. Both BN groups had substantially lower Bmax than did healthy controls. Our results corroborate other findings indicating recovered BN patients to have anomalous 5-HT functioning. While such effects could represent a lasting 'injury' to the system, reported covariations between personality traits and 5-HT indices in BN encourage us to favor the argument that some alterations of 5-HT activity (in this case, consistent with reduced transporter activity) represent a 'trait' associated with the risk of developing BN and/or associated psychopathology. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]