D. Blake Woodside

The prevalence of high-level exercise in the eating disorders: Etiological implications

There is increasing evidence both from animal experimentation and from clinical field studies that physical activity can play a central role in the pathogenesis of some eating disorders. However, few studies have addressed the issue of prevalence or whether there are different rates of occurrence across diagnostic categories, and the estimates that do exist are not entirely satisfactory. The present study was designed to conduct a detailed examination of the physical activity history in patients with anorexia nervosa (AN) and bulimia nervosa (BN) both during and prior to the onset of their disorder. A sample of adult patients and a second sample of adolescent AN patients took part in the study. A series of chi-square analyses compared diagnostic groups on a number of variables related to sport/exercise behaviors both premorbidly and comorbidly. Data were obtained by means of a detailed structured interview with each patient. We found that a large proportion of eating disorder patients were exercising excessively during an acute phase of the disorder, overexercising is significantly more frequent among those with AN versus BN, and premorbid activity levels significantly predict excessive exercise comorbidity. These findings underscore the centrality of physical activity in the development and maintenance of some eating disorders. They also have important clinical implications in light of the large proportion of individuals who combine dieting and exercise in an attempt to lose weight, and the increasing recognition of the adverse effects of strenuous physical activity in malnourished individuals.

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.

Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial

BACKGROUND Anorexia nervosa is characterised by a chronic course that is refractory to treatment in many patients and has one of the highest mortality rates of any psychiatric disorder. Deep brain stimulation (DBS) has been applied to circuit-based neuropsychiatric diseases, such as Parkinsons disease and major depression, with promising results. We aimed to assess the safety of DBS to modulate the activity of limbic circuits and to examine how this might affect the clinical features of anorexia nervosa. METHODS We did a phase 1, prospective trial of subcallosal cingulate DBS in six patients with chronic, severe, and treatment-refractory anorexia nervosa. Eligible patients were aged 20-60 years, had been diagnosed with restricting or binge-purging anorexia nervosa, and showed evidence of chronicity or treatment resistance. Patients underwent medical optimisation preoperatively and had baseline body-mass index (BMI), psychometric, and neuroimaging investigations, followed by implantation of electrodes and pulse generators for continuous delivery of electrical stimulation. Patients were followed up for 9 months after DBS activation, and the primary outcome of adverse events associated with surgery or stimulation was monitored at every follow-up visit. Repeat psychometric assessments, BMI measurements, and neuroimaging investigations were also done at various intervals. This trial is registered with ClinicalTrials.gov, number NCT01476540. FINDINGS DBS was associated with several adverse events, only one of which (seizure during programming, roughly 2 weeks after surgery) was serious. Other related adverse events were panic attack during surgery, nausea, air embolus, and pain. After 9 months, three of the six patients had achieved and maintained a BMI greater than their historical baselines. DBS was associated with improvements in mood, anxiety, affective regulation, and anorexia nervosa-related obsessions and compulsions in four patients and with improvements in quality of life in three patients after 6 months of stimulation. These clinical benefits were accompanied by changes in cerebral glucose metabolism (seen in a comparison of composite PET scans at baseline and 6 months) that were consistent with a reversal of the abnormalities seen in the anterior cingulate, insula, and parietal lobe in the disorder. INTERPRETATION Subcallosal cingulate DBS seems to be generally safe in this sample of patients with chronic and treatment-refractory anorexia nervosa. FUNDING Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research.

Significant Linkage on Chromosome 10p in Families with Bulimia Nervosa

Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n=133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.

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.

Association of multiple DRD2 polymorphisms with anorexia nervosa.

To investigate whether the dopaminergic system plays a role in the etiology of anorexia nervosa (AN) via the dopamine D2 receptor, we investigated association and transmission disequilibrium at seven single-nucleotide polymorphisms (SNPs) spanning about 75 kbp of the gene DRD2. We studied 191 probands with a DSM-IV diagnosis of AN, 457 parents and affected relatives with a DSM-IV eating disorder diagnosis, and 98 unrelated, female, normal weight controls. The −141 C/− insertion/deletion (−141 Indel), previously shown to affect DRD2 transcription efficiency, and multiple exon seven polymorphisms, one of which has previously been shown to affect DRD2 transcript stability, exhibited statistically significant association with diagnosis in haplotype transmission disequilibrium and in haplotype case : control analyses. Significant linkage disequilibrium between the −141 Indel and two exon seven SNPs (939Y and 957Y) was observed over a distance of >50 kbp in the AN probands but not in the controls. Genetically transmitted variation in D2 dopamine receptor expression mediated by functional polymorphisms affecting transcription and translation efficiency may play a role in vulnerability to AN.

Impulse control disorders in women with eating disorders.

We compared symptom patterns, severity of illness, and comorbidity in individuals with eating disorders with and without impulse control disorders (ICD), and documented the temporal pattern of illness onset. Lifetime ICD were present in 16.6% of 709 women with a history of eating disorders. The most common syndromes were compulsive buying disorder and kleptomania. ICD occurred more in individuals with binge eating subtypes, and were associated with significantly greater use of laxatives, diuretics, appetite suppressants and fasting, and with greater body image disturbance, higher harm avoidance, neuroticism, cognitive impulsivity, and lower self-directedness. In addition, individuals with ICD were more likely to have obsessive-compulsive disorder, any anxiety disorder, specific phobia, depression, cluster B personality disorder, avoidant personality disorder, and to use psychoactive substances. Among those with ICD, 62% reported the ICD predated the eating disorder and 45% reported the onset of both disorders within the same 3-year window. The presence of a lifetime ICD appears to be limited to eating disorders marked by binge eating and to be associated with worse eating-related psychopathology, more pathological personality traits, and more frequent comorbid Axis I and II conditions. Untreated ICD may complicate recovery from eating disorders.

Suicide attempts in anorexia nervosa.

Objective: To explore prevalence and patterns of suicidal attempts in persons with anorexia nervosa (AN). Methods: Participants were the first 432 persons (22 male, 410 female) enrolled in the NIH funded Genetics of Anorexia Nervosa Collaborative Study. All participants had current or lifetime AN. The participants ranged in age from 16 to 76 (mean = 30.4, SD = 11.3). Suicidal behavior and intent was assessed via the Diagnostic Interview for Genetic Studies. We compared frequency and severity of attempts across diagnostic subtypes and comorbidity, and personality features associated with the presence of suicide attempts in persons with AN. Results: About 16.9% of those with AN attempted suicide. Significantly fewer persons with the restricting subtype (7.4%) reported at least one attempt than those with purging AN (26.1%), AN with binge eating (29.3%), and a mixed picture of AN and bulimia nervosa (21.2%). After controlling for major depression, suicide attempts were associated with substance abuse, impulsive behaviors and traits, Cluster B personality disorders, panic disorder, and post-traumatic stress disorder as well as low self-directedness and eating disorder severity. Conclusions: Suicide attempts in AN are not uncommon, are frequently associated with the intention to die, occur less frequently in persons with the restricting subtype of the illness, and after controlling for depression are associated with a constellation of behaviors and traits associated with behavioral and affective dyscontrol. AN = anorexia nervosa; BN = bulimia nervosa; RAN = restricting anorexia nervosa; PAN = purging anorexia nervosa; AN(B) = binging anorexia nervosa; EDNOS = eating disorder not otherwise specified; ANBN = lifetime history of both AN and BN.

Age of onset in eating disorders

This paper presents age of onset data for anorexia nervosa and bulimia nervosa, derived from a sample of 323 patients referred to a tertiary referral center. Patients had anorexia nervosa (n = 39), bulimia nervosa (n = 173), or bulimia nervosa with a history of anorexia nervosa (n = 173). While the pattern of onset of anorexia nervosa and bulimia nervosa is similar up to age 25, there is a significant excess of new cases of anorexia nervosa beyond this point. Significantly, age of onset was constant for both anorexia nervosa and bulimia regardless of whether they occurred in isolation (anorexia or bulimia alone) or in concert in the same individual (bulimia with a history of anorexia nervosa).

A prospective study of predictors of relapse in anorexia nervosa: Implications for relapse prevention

Anorexia nervosa (AN) is a serious psychiatric disorder with a high rate of relapse. The goal of this study was to identify predictors of relapse in adult AN using a prospective, longitudinal design. Participants were 100 AN patients who had successfully completed specialized inpatient/day treatment, were weight-restored to a body mass index (BMI) of at least 20 for a minimum of 2 weeks, and reported less than one binge-purge (BP) episode over the previous 28 days at the end of treatment. Predictor variables included baseline demographic and clinical features, behavioral and psychological changes during treatment, residual psychopathology at post-treatment, and motivation to recover. Results indicated that 41% of participants relapsed during the 1-year follow-up period. The highest risk period for relapse was between 4 and 9 months post-treatment. Predictors of relapse included: the BP subtype of AN, severity of checking behaviors at pre-treatment, decrease in motivation to recover during treatment, and lower motivation to recover at post-treatment. These findings suggest that individuals with the BP subtype of AN are particularly susceptible to relapse. Increasing and maintaining motivation to recover during acute treatment may have an important impact on long-term outcome.