Lisa R. Lilenfeld

Temperament and character in women with anorexia nervosa

The present study examined temperament differences among anorexia nervosa (AN) subtypes and community controls, as well as the effect of body weight on personality traits in women with AN. Temperament and Character Inventory (TCI) scores were compared between 146 women with restrictor-type AN (RAN), 117 women with purging-type AN (PAN), 60 women with binge/purge-type AN (BAN), and 827 community control women (CW) obtained from an archival normative database. Women with AN scored significantly higher on harm avoidance and significantly lower on cooperativeness than CW. Subtype analyses revealed that women with RAN and PAN reported the lowest novelty seeking, RAN women the highest persistence and self-directedness, and PAN women the highest harm avoidance. Body mass index had a nominal effect on subgroup differences, suggesting that personality disturbances are independent of body weight. Findings suggest that certain facets of temperament differ markedly between women with AN, regardless of diagnostic subtype, and controls. More subtle temperament and character differences that were independent of body weight emerged that distinguish among subtypes of AN.

A search for susceptibility loci for anorexia nervosa: methods and sample description

BACKGROUND Eating disorders have not traditionally been viewed as heritable illnesses; however, recent family and twin studies lend credence to the potential role of genetic transmission. The Price Foundation funded an international, multisite study to identify genetic factors contributing to the pathogenesis of anorexia nervosa (AN) by recruiting affective relative pairs. This article is an overview of study methods and the clinical characteristics of the sample. METHODS All probands met modified DSM-IV criteria for AN; all affected first, second, and third degree relatives met DSM-IV criteria for AN, bulimia nervosa (BN), or eating disorder not otherwise specified (NOS). Probands and affected relatives were assessed diagnostically with the Structured Interview for Anorexia and Bulimia. DNA was collected from probands, affected relatives and a subset of their biological parents. RESULTS Assessments were obtained from 196 probands and 237 affected relatives, over 98% of whom are of Caucasian ancestry. Overall, there were 229 relative pairs who were informative for linkage analysis. Of the proband-relative pairs, 63% were AN-AN, 20% were AN-BN, and 16% were AN-NOS. For family-based association analyses, DNA has been collected from both biological parents of 159 eating-disordered subjects. Few significant differences in demographic characteristics were found between proband and relative groups. CONCLUSIONS The present study represents the first large-scale molecular genetic investigation of AN. Our successful recruitment of over 500 subjects, consisting of affected probands, affected relatives, and their biological parents, will provide the basis to investigate genetic transmission of eating disorders via a genome scan and assessment of candidate genes.

A family history study of binge-eating disorder ☆

Family studies of anorexia nervosa and bulimia nervosa have yielded important information about the etiologies of these eating disorders. By contrast, little is known about familial factors of etiologic importance for binge-eating disorder (BED). The purpose of the current family history study was to assess the prevalence of comorbid psychopathology in a non-treatment seeking female sample of 31 probands with BED, 32 control probands without BED, and their 283 first-degree relatives. In-person semistructured clinical interviews were conducted with the probands, who also served as informants for all of their first-degree relatives. Significantly higher lifetime rates of major depressive disorder, dysthymic disorder, and social phobia were found among women with BED compared with control women. Significantly higher lifetime rates of bipolar (I or II) disorder, any depressive disorder, nearly all anxiety disorders, anorexia nervosa, and BED were reported among the first-degree relatives of women with BED compared with the first-degree relatives of control women. Furthermore, female relatives of women with BED were reported to have higher rates of substance use disorders and dysthymic disorder compared with female relatives of control women without BED. Nearly all disorders that were elevated in relatives of women with BED followed a pattern of independent transmission from BED. The primary exception was substance use disorder among female relatives, whose transmission pattern was consistent with that of a shared etiology with BED. Thus, BED and substance use disorder may share a common mechanism of familial transmission among women.

Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

Features associated with laxative abuse in individuals with eating disorders

Objective: Laxative abuse is common in patients with anorexia and bulimia nervosa and has been associated with longer duration of illness, suicide attempts, impulsivity, and greater eating and general psychopathology. We explored the extent to which laxative abuse was associated with specific psychopathological features across eating disorder subtypes. Methods: Participants were 1021 individuals from the multisite, International Price Foundation Genetic Studies. Axis I disorders, personality disorders and traits, and obsessive compulsive features were assessed. Results: Laxative abuse was associated with worse eating disorder and general psychopathology and higher prevalence of borderline personality disorder (BPD). Symptom level analyses revealed that specific features of BPD, including suicidality and self-harm, feelings of emptiness, and anger, were most strongly associated with laxative abuse. Conclusions: The function of laxative abuse may differ across individuals with eating disorders, alternatively serving as a method of purging and a form of self-harm. ED = eating disorder; AN = anorexia nervosa; BN = bulimia nervosa; PAN = purging anorexia nervosa; BAN = binge-purge anorexia nervosa; PBN = purging bulimia nervosa; EDNOS = eating disorders not otherwise specified; ANBN = individuals with both a history of anorexia and bulimia nervosa; BPD = borderline personality disorder; PTSD = posttraumatic stress disorder; BMI = body mass index; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; SCID-I and -II = Structured Clinical Interview for DSM-IV for Axis I and Axis II disorders; SIAB = Structured Inventory of Anorexia Nervosa and Bulimic Syndromes; TCI = Temperament and Character Inventory; MPS = Multidimensional Perfectionism Scale; YBOCS = Yale-Brown Obsessive Compulsive Scale; YBC-EDS = Yale-Brown-Cornell Eating Disorder Scale; GEE = generalized estimating equations.

Placebo response in binge eating disorder

Objective: Placebo response in studies of binge eating disorder (BED) has raised concern about its diagnostic stability. The aims of this study were (1) to compare placebo responders (PRs) with nonresponders (NRs); (2) to investigate the course of BED following placebo response; and (3) to examine attributions regarding placebo response. Method: The baseline placebo run-in phase (BL) was part of a RCT investigating sibutramine hydrochloride for BED; it included 451 participants, ages 19–63, diagnosed with BED. Follow-up (FU) included 33 PRs. Results: In this study, 32.6% of participants responded to placebo (PRs = 147; NRs = 304). PRs exhibited significantly less symptom severity. At FU (n = 33), many PRs reported continued symptoms. Conclusion: PRs exhibited significantly less severe pathology than NRs. Placebo response in BED may transitory or incomplete. The results of this study suggest variable stability in the BED diagnosis.

Personality and Temperament

The assessment of personality and temperament in the context of eating disorders (EDs) poses unique challenges because of the physiological symptoms and sequelae of these illnesses. Four models of the relationship between personality and EDs are presented, along with a discussion of the different methodological designs which can evaluate these models. Current data support the likelihood that neuroticism and perfectionism are risk factors for EDs. Perfectionism and the related obsessive-compulsive personality disorder may also share a common cause with anorexia nervosa. High harm avoidance and low self-directedness also characterize all EDs, though more data are needed to confirm their role as risk factors; importantly however, this combination of traits may diminish ones ability to cope with stressful life events. At the other end of the spectrum, considering impulsivity multidimensionally may be important to understanding the role of this personality trait in EDs, though existing data do not yet allow for conclusions regarding its role as a risk factor versus a consequence of the ED. All of the identified traits that may be risk factors are also exacerbated as a consequence of having, or having had, an ED. Finally, the role of personality disorders in influencing the course and outcome of EDs is still unclear. A fruitful avenue for future research in this area is to utilize personality and temperament to classify individuals in a way that allows for the best chance of identifying genetic loci that confer increased risk for EDs.

Characterization of genetic variation in the VGLL4 gene in anorexia nervosa

Reference EPFL-ARTICLE-201159doi:10.1097/Ypg.0000000000000040View record in Web of Science Record created on 2014-08-29, modified on 2017-05-12

Suicidal Behavior in Eating Disorders

Anorexia nervosa has the highest mortality rate of any psychiatric illness, with suicide being the second leading cause of death. In addition to frank suicide attempts (some of which are premeditated and some of which are impulsive), many individuals with eating disorders engage in other intentional forms of self-injury, especially those individuals with purging symptomatology. In fact, those who use multiple purging strategies are especially likely to attempt suicide. Prospective predictors of suicidality in this population include having a co-morbid substance use disorder and engaging in laxative abuse. In addition, multiple forms of impulsive behavior are common among those individuals with eating disorders who have attempted suicide. Clinicians working with an eating disordered population must be aware of the high risk of suicidality in order to appropriately assess for, and monitor this risk vigilantly throughout treatment, because we now know that heightened suicide risk may continue even after eating disorder symptoms begin to improve. Thus, careful assessment of suicidal ideation, as well as degree of lethality and intent to die, must be part of the initial, as well as ongoing assessment, in the treatment of individuals with eating disorders.