Diane A. Klein

Eating disorders: clinical features and pathophysiology

Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders of eating and weight-related behavior that together afflict some 1-3% of women in the United States. One of the remarkable features about each of the eating disorders is how persistent the disordered eating behavior becomes once it has begun. Substantial psychological, social, and physiological disturbances are associated with eating disorders, and it has been very difficult to disentangle those factors that may result from the disturbed behavior from the factors that may have predisposed individuals to, or precipitated the development of, the disorder. This article will briefly review the definitions, phenomenology, and identified risk factors for development of each of the major eating disorders. Pathophysiology will be discussed, with a particular focus on candidate factors that might sustain disordered eating behavior, as informed by clinical and basic science research. Future research directions will be suggested.

Adipose tissue distribution after weight restoration and weight maintenance in women with anorexia nervosa

BACKGROUND Body image distortions are a core feature of anorexia nervosa (AN). We, and others, previously reported abnormalities in adipose tissue distribution after acute weight restoration in adult women with AN compared with body mass index-matched healthy control women. Whether these abnormalities persist over time remains unknown. OBJECTIVES We aimed to 1) replicate previous findings that showed preferential central accumulation of adipose tissue in recently weight-restored AN women compared with control subjects, 2) describe the change within patients with longer-term (1-y) weight maintenance, and 3) compare adipose tissue distribution after 1-y maintenance with that of control subjects. DESIGN Body composition and adipose tissue distribution were assessed by whole-body magnetic resonance imaging in women with AN shortly after weight normalization (n = 30) and again 1 y after hospital discharge (n = 16) and in 8 female control subjects at 2 time points. RESULTS With acute weight restoration, AN patients had significantly greater visceral and intermuscular adipose tissue compared with control women [visceral: 0.75 +/- 0.26 compared with 0.51 +/- 0.26 kg in AN patients and controls, respectively (P = 0.02); intermuscular: 0.46 +/- 0.17 compared with 0.29 +/- 0.13 kg in AN patients and controls, respectively (P = 0.01)]. With maintenance of normal weight for approximately 1 y, visceral adipose tissue distribution in AN patients was not different from that in healthy control subjects. CONCLUSIONS In adult women with AN, normalization of weight in the short term is associated with a distribution of adipose tissue that is consistent with a central adiposity phenotype. This abnormal distribution appears to normalize within a 1-y period of weight maintenance. This research was registered at clinicaltrials.gov as NCT 00271921 and NCT 00368667.

Modified sham feeding of sweet solutions in women with anorexia nervosa

Anorexia Nervosa (AN) is a disorder of self-starvation characterized by decreased meal size and food intake. While it is possible that reduced food intake in AN reflects an excess of inhibitory factors, e.g., cognitive inhibition related to fear of weight gain or abnormal postingestive negative feedback, it is also possible that decreased intake reflects diminished orosensory stimulation of food intake. This has been difficult to test directly because the amount of food ingested during a test meal by patients with AN reflects an integration of orosensory excitatory, and cognitive, learned, and postingestive inhibitory controls of eating. To begin to dissociate these controls, we adapted the modified sham feeding technique (MSF) to measure the intake of a series of sweetened solutions in the absence of postingestive stimulation. Subjects with AN (n=24) and normal controls (NC, n=10) were randomly presented with cherry Kool Aid solutions sweetened with five concentrations of aspartame (0, 0.01, 0.03, 0.08 and 0.28%) in a closed opaque container fitted with a straw. They were instructed to sip as much as they wanted of the solution during 15 1-minute trials and to spit the fluid out into another opaque container. Subjects with AN sipped less unsweetened solution than NC (p<0.05). Because this difference appeared to account completely for the smaller intakes of sweetened solutions by AN, responsiveness of intake to sweet taste per se was not different in AN and NC. Since MSF eliminated postingestive and presumably cognitive inhibitory controls, and the orosensory response to sweet taste was not different in AN than NC, we conclude that decreased intake by AN subjects under these conditions reflects the increased inhibition characteristic of this disorder that is presumably learned, with a possible contribution of decreased potency of orosensory stimulation by the sipped solutions.

Intake, sweetness and liking during modified sham feeding of sucrose solutions

Although sweet solids and liquids are palatable to humans and ingested frequently when readily available, the quantitative relationship between sweet taste and intake has not been reported in humans. To investigate the quantitative relationship between sweet taste and intake directly, we adapted the modified sham feeding technique, previously used in humans for the study of the orosensory control of autonomic, neuroendocrine, and metabolic mechanisms, to measure the intake of solutions both unsweetened and sweetened with four concentrations of sucrose. By limiting the sucrose stimuli to the mouth, the modified sham feeding technique measures the orosensory stimulation of intake by sucrose in the absence of inhibitory postingestive stimulation. Nine healthy women were randomly presented with two series of five solutions of cherry Kool Aid unsweetened or sweetened with one of four concentrations of sucrose (2.5%, 5%, 10%, or 20%) in a closed opaque container fitted with a straw. They were instructed to sip as much as they wanted of the liquid during 2-min trials and to spit the fluid out into another opaque container. At the end of each trial, they used Visual Analogue Scales to rate the perceived intensities of sweetness and liking of the liquid that they had just sipped and spit. Intake, liking and perceived sweetness were significantly affected by sucrose concentration (p values</=0.038). Intake at 20% was not significantly larger than 10% or 5%. The effects of sucrose were presumably due to orosensory stimulation in the absence of postingestive stimulation because the amount of liquid spit out did not differ significantly from the amount sipped.

Physical activity and post‐treatment weight trajectory in anorexia nervosa

OBJECTIVE This study compared an objective measurement of physical activity (PA) in individuals with anorexia nervosa (AN) at low-weight, weight-restored, and post-treatment time points, and also compared PA in AN with that of healthy controls (HC). METHOD Sixty-one female inpatients with AN wore a novel accelerometer (the IDEEA) which measured PA at three time points: a) low-weight, b) weight-restored, and c) one month post-hospital discharge. Twenty-four HCs wore the IDEEA at one time point. RESULTS Inpatients with AN became more physically active than they were at low-weight at weight restoration and following treatment discharge. Post-treatment patients with AN were more physically active than HCs during the day and less active at night, which was primarily accounted for by amount of time spent on feet, including standing and walking. Greater time spent on feet during the weight-restoration time point of inpatient treatment was associated with more rapid decrease in BMI over the 12 months following treatment discharge. Fidgeting did not differ between patients and controls, did not change with weight restoration, and did not predict post-treatment weight change. DISCUSSION Use of a novel accelerometer demonstrated greater PA in AN than in HC. PA following weight restoration in AN, particularly time spent in standing postures, may contribute to weight loss in the year following hospitalization.

Assessment of fat taste in individuals with and without anorexia nervosa

OBJECTIVE Avoidance of dietary fat is a highly characteristic eating behavior of individuals with anorexia nervosa (AN). To date, no study has determined whether these individuals are better able to perceive the fat content of foods than individuals without AN. The goal of this study was to compare blinded taste ratings of fat-free, low fat, and regular cream cheese in patients with AN and in normal controls (NC). METHOD AN (n = 25) and control (NC; n = 25) participants were presented with a series of nine cream cheese samples of three differing fat contents and asked to taste and rate each sample from very low to very high fat. RESULTS Repeated measures ANOVA found no significant main effect of fat content and no interaction between fat content and diagnosis; however, a significant three-way interaction between fat content, diagnosis, and trial was observed. Post hoc analysis revealed a significant fat content by trial interaction within the AN group, suggesting a significant trial effect for the fat-free samples only with improving ability to detect fat-free samples over repeated trials. DISCUSSION The current study suggests that individuals with AN do not have a markedly greater ability to taste fat than NC, and that; therefore, fat avoidance is likely primarily based on cognitive factors.

Exercise Reinforcement, Stress, and β-endorphins: An Initial Examination of Exercise in Anabolic-Androgenic Steroid Dependence

BACKGROUND Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. METHOD Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. RESULTS Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. CONCLUSION The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.

Measurement of fidgeting in patients with anorexia nervosa using a novel shoe-based monitor

OBJECTIVE To objectively assess seated non-exercise physical activity in patients with anorexia nervosa (AN) relative to healthy controls (HCs) and examine the associations between this physical activity, eating disorder pathology, and levels of anxiety and depression. METHOD Eleven inpatients with AN and 10 HCs wore a shoe-based accelerometer (SmartShoe) at three time points: a) while eating lunch, b) filling out questionnaires, and c) watching television for 1h. RESULTS Across all three tasks, patients with AN were significantly more active than HCs, thereby engaging in a greater degree of restless or fidgeting behavior. Degree of physical activity was positively correlated with eating disorder psychopathology in the sample with AN, and a trend towards a positive association between physical activity and levels of depression and anxiety was also found in this sample. Among individuals with AN, physical activity was not significantly correlated with BMI, duration of illness, or number of days since hospital admission. DISCUSSION Use of a minimally invasive, shoe-based monitor revealed patients with AN engaged in a greater degree of fidgeting relative to HCs during quiet, seated tasks and this heightened activity was related to measures of pathology. Non-exercise physical activity, including fidgeting, may warrant further clinical attention in this patient population.

Assessment of the motivation to use artificial sweetener among individuals with an eating disorder

Eating disorders are associated with a range of abnormalities in eating behavior. Some individuals consume large amounts of non-caloric artificial sweeteners, suggesting abnormalities in appetitive responding. The current study aimed to quantify hedonic and motivating effects of artificial sweetener in individuals with and without an eating disorder. Two laboratory studies were conducted. Hedonic preference was estimated using the number of artificial sweetener packets (0-10) added to unsweetened cherry flavored Kool-Aid (study 1). Motivation to obtain sweetener was assessed by a progressive ratio (PR) work task (study 2). Ninety-three participants (25 anorexia nervosa restricting type (AN-R), 23 AN binge/purge type (AN-B/P), 20 bulimia nervosa (BN), and 25 normal controls (NC)) completed the study. No significant difference in hedonic preference was found among participant groups. Work completed at the PR task ranged from 0 to 9500 key-board presses. The AN-B/P group had a significantly higher breakpoint and performed significantly more work for sweetener compared to the BN and NC groups. Among AN-B/P and AN-R participants, the preferred number of Equal packets was significantly correlated with the breakpoint and total work. The increased amount of work for sweetener among individuals with AN-B/P supports an enhanced reward value of sweet taste in this population, and suggests that the characteristic food avoidance in AN cannot be accounted for by decreased reward value of all taste-related stimuli. This study also supports the novel application of a PR ratio task to quantify the motivating effect of sweet taste among individuals with an eating disorder.

Validation of two novel monitoring devices to measure physical activity in healthy women.

Measurement of physical activity is increasingly important in health research. We sought to determine the accuracy and sensitivity to non-exercise activity of three activity monitors worn simultaneously by healthy adult women participating in a structured activity protocol. Ten normal-weight women wore the Intelligent Device for Energy Expenditure and Activity (IDEEA), the SmartShoe, and the SenseWear Armband, during activities that included standing, sitting still, sitting and fidgeting, lying down, and walking at varying speeds. Percentage of time postures correctly identified was determined for the IDEEA and the SmartShoe, and activity counts collected from all three devices were compared. Posture was detected with high accuracy by both the IDEEA and the SmartShoe (97.4% and 94.2% accuracy, respectively). The SmartShoe showed superior sensitivity to movement while seated (“fidgeting”) compared with the IDEEA (p=0.004 and 0.049 difference between postures, respectively); all three devices distinguished between fast and slow walking. Data support the ability of the IDEEA and the SmartShoe to recognize basic postures in healthy normal-weight women, as well as to detect fidgeting within the seated position.