Self-referential processing in anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a serious psychiatric illness associated with significant medical and psychiatric comorbidity and impairment. Theoretical models of AN and self-report studies suggest that negative self-evaluation (i.e., low self-esteem) is related to the development and maintenance of AN. The goal of this study was to extend findings from self-report methodology using a neurocognitive task that probes self-evaluation implicitly and explicitly. METHOD: We compared female adolescent and adult patients with AN (n = 35) and healthy controls (HC, n = 38) on explicit (i.e., endorsement of words as self-relevant), implicit (recall, recognition, reaction time), and composite (i.e., valence index, bias score, drift rates) indices of self-evaluation. We applied a drift-diffusion model to compute the drift rates, reflecting participants' decision-making process as to whether words were self-relevant. The association between self-evaluation indices and eating disorder severity was examined. RESULTS: There were significant Group × Condition interaction effects for all explicit and implicit measures (all p's ≤ .01), where the AN group endorsed, recalled, and recognized more negative relative to positive words than HC. The AN group had more negative valence index and bias scores, and slower drift rate away from negative words, reflecting more negative self-evaluation. The finding for recall was attenuated when individuals with depression were excluded. Measures of self-evaluation bias were not related to eating disorder severity. DISCUSSION: Using a neurocognitive approach that includes explicit and implicit indices of bias, results suggest that patients with AN have more negative self-evaluation. Due to the cross-sectional design, additional studies are needed to further evaluate directionality. PUBLIC SIGNIFICANCE: Negative self-evaluation/low self-esteem is thought to contribute to eating disorder symptoms. Findings of this study using a neurocognitive task to probe self-evaluation suggested that individuals with anorexia nervosa have more negative self-evaluation, reflected by endorsing and remembering more negative (than positive) words compared to healthy controls, and doing so faster. Targeting the construct of negative self-evaluation in treatment of AN may be warranted.

Reduced dorsal fronto-striatal connectivity at rest in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear. METHODS: The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality. RESULTS: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality. CONCLUSIONS: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

The explore/exploit trade-off: An ecologically valid and translational framework that can advance mechanistic understanding of eating disorders.

The explore/exploit trade-off is a decision-making process that is conserved across species and balances exploring unfamiliar choices of unknown value with choosing familiar options of known value to maximize reward. This framework is rooted in behavioral ecology and has traditionally been used to study maladaptive versus adaptive non-human animal foraging behavior. Researchers have begun to recognize the potential utility of understanding human decision-making and psychopathology through the explore/exploit trade-off. In this article, we propose that explore/exploit trade-off holds promise for advancing our mechanistic understanding of decision-making processes that confer vulnerability for and maintain eating pathology due to its neurodevelopmental bases, conservation across species, and ability to be mathematically modeled. We present a model for how suboptimal explore/exploit decision-making can promote disordered eating and present recommendations for future research applying this framework to eating pathology. Taken together, the explore/exploit trade-off provides a translational framework for expanding etiologic and maintenance models of eating pathology, given developmental changes in explore/exploit decision-making that coincide in time with the emergence of eating pathology and evidence of biased explore/exploit decision-making in psychopathology. Additionally, understanding explore/exploit decision-making in eating disorders may improve knowledge of their underlying pathophysiology, informing targeted clinical interventions such as neuromodulation and pharmacotherapy. PUBLIC SIGNIFICANCE STATEMENT: The explore/exploit trade-off is a cross-species decision-making process whereby organisms choose between a known option with a known reward or sampling unfamiliar options. We hypothesize that imbalanced explore/exploit decision-making can promote disordered eating and present preliminary data. We propose that explore/exploit trade-off has significant potential to advance understanding of the neurocognitive and neurodevelopmental mechanisms of eating pathology, which could ultimately guide revisions of etiologic models and inform novel interventions.

El balance entre explorar y explotar es un proceso de toma de decisiones que se conserva a través de las especies y equilibra la exploración de opciones desconocidas de valor desconocido con la elección de opciones familiares de valor conocido para maximizar la recompensa. Este marco está arraigado en la ecología del comportamiento y tradicionalmente se ha utilizado para estudiar el comportamiento de forrajeo no adaptativo versus adaptativo en animales no humanos. Los investigadores han comenzado a reconocer la utilidad potencial de entender la toma de decisiones humanas y la psicopatología a través del balance entre explorar y explotar. En este artículo, proponemos que el balance entre explorar y explotar ofrece promesas para avanzar en nuestra comprensión mecanicista de los procesos de toma de decisiones que confieren vulnerabilidad y mantienen la patología alimentaria debido a sus bases neurodesarrolladoras, su conservación a través de las especies y su capacidad de ser modelado matemáticamente. Presentamos un modelo de cómo la toma de decisiones subóptima entre explorar y explotar puede promover la alimentación disfuncional y presentamos recomendaciones para futuras investigaciones que apliquen este marco a la patología alimentaria. En conjunto, el balance entre explorar y explotar proporciona un marco translacional para expandir los modelos etiológicos y de mantenimiento de la patología alimentaria, dadas los cambios en el desarrollo de la toma de decisiones entre explorar y explotar que coinciden en el tiempo con la aparición de la patología alimentaria y la evidencia de una toma de decisiones entre explorar y explotar sesgada en la psicopatología. Además, comprender la toma de decisiones entre explorar y explotar en los trastornos alimentarios puede mejorar el conocimiento de su fisiopatología subyacente, informando intervenciones clínicas dirigidas como la neuromodulación y la farmacoterapia.

Time to revisit the definition of atypical anorexia nervosa.

In this special issue, international researchers investigate how atypical anorexia nervosa (atypical AN) differs from anorexia nervosa (AN) and other eating disorders with respect to demographics, psychological and physiological morbidity, as well as treatment course and outcome. Manuscripts in this special issue report that atypical AN is associated with substantial medical and psychological morbidity, and the majority of studies find few differences between atypical AN and AN. While much remains to be learned about the long-term course and treatment response of individuals with atypical AN to psychological and pharmacological interventions, the evidence supports conceptualization of atypical AN as part of a spectrum-based restrictive eating disorder. These findings together with the potentially stigmatizing use of the term "atypical" suggest it may be time to revise the existing definition of atypical AN.

Change in food choice during acute treatment and the effect on longer-term outcome in patients with anorexia nervosa.

BACKGROUND: Restriction of food intake is a central pathological feature of anorexia nervosa (AN). Maladaptive eating behavior and, specifically, limited intake of calorie-dense foods are resistant to change and contribute to poor long-term outcomes. This study is a preliminary examination of whether change in food choices during inpatient treatment is related to longer-term clinical course. METHODS: Individuals with AN completed a computerized Food Choice Task at the beginning and end of inpatient treatment to determine changes in high-fat and self-controlled food choices. Linear regression and longitudinal analyses tested whether change in task behavior predicted short-term outcome (body mass index [BMI] at discharge) and longer-term outcome (BMI and eating disorder psychopathology). RESULTS: Among 88 patients with AN, BMI improved significantly with hospital treatment (p < 0.001), but Food Choice Task outcomes did not change significantly. Change in high-fat and self-controlled choices was not associated with BMI at discharge (r = 0.13, p = 0.22 and r = 0.10, p = 0.39, respectively). An increase in the proportion of high-fat foods selected (ß = 0.91, p = 0.02) and a decrease in the use of self-control (ß = -1.50, p = 0.001) predicted less decline in BMI over 3 years after discharge. CONCLUSIONS: Short-term treatment is associated with improvement in BMI but with no significant change, on average, in choices made in a task known to predict actual eating. However, the degree to which individuals increased high-fat choices during treatment and decreased the use of self-control over food choice were associated with reduced weight loss over the following 3 years, underscoring the need to focus on changing eating behavior in treatment of AN.

Heightened sensitivity to high-calorie foods in children at risk for obesity: insights from behavior, neuroimaging, and genetics.

Pediatric obesity is a major public health concern. Genetic susceptibility and increased availability of energy-dense food are known risk factors for obesity. However, the extent to which these factors jointly bias behavior and neural circuitry towards increased adiposity in children remains unclear. While undergoing fMRI, 108 children (ages 5-11y) performed a food-specific go/no-go task. Participants were instructed to either respond ("go") or inhibit responding ("no-go") to images of food or toys. Half of the runs depicted high-calorie foods (e.g., pizza) whereas the other half depicted low-calorie foods (e.g., salad). Children were also genotyped for a DNA polymorphism associated with energy intake and obesity (FTO rs9939609) to examine the influence of obesity risk on behavioral and brain responses to food. Participants demonstrated differences in behavioral sensitivity to high- and low-calorie food images depending on task demands. Participants were slower but more accurate at detecting high- (relative to low-) calorie foods when responding to a neutral stimulus (i.e., toys) and worse at detecting toys when responding to high-calorie foods. Inhibition failures were accompanied by salience network activity (anterior insula, dorsal anterior cingulate cortex), which was driven by false alarms to food images. Children at a greater genetic risk for obesity (dose-dependent model of the FTO genotype) demonstrated pronounced brain and behavioral relationships such that genetic risk was associated with heightened sensitivity to high-calorie food images and increased anterior insula activity. These findings suggest that high-calorie foods may be particularly salient to children at risk for developing eating habits that promote obesity.

A systematic review comparing atypical anorexia nervosa and anorexia nervosa.

OBJECTIVE: A description of atypical anorexia nervosa (atypical AN) was provided in DSM-5 in 2013 and a sizable literature has since developed describing the clinical features of individuals with atypical AN and comparing them to those of individuals with anorexia nervosa (AN) and those of healthy individuals. The purpose of this study was to conduct a systematic review of this literature. METHOD: A systematic review following PRISMA guidelines was conducted of studies published since 2013 that compared the clinical characteristics of individuals with atypical AN to those of individuals with AN and/or healthy controls. Meta-analyses were conducted when similar measures were reported in three or more studies. RESULTS: Twenty-four publications met criteria for inclusion. Their results indicated that the level of eating disorder-specific psychopathology is significantly higher among individuals with atypical AN than among controls and as high or higher as among individuals with AN while levels of non-eating disorder psychopathology are similar. Individuals with atypical AN experience many of the physiological complications associated with AN, but some complications appear less frequent. DISCUSSION: The psychological symptoms and physiological complications of individuals with atypical AN are generally similar to those of individuals with AN, although there may be differences in the frequency of some physical complications. Little information is available on the course, outcome, and treatment response of individuals with atypical AN. In addition, full diagnostic criteria for atypical AN have not been developed, and the nosological relationship of atypical AN to established eating disorders such as bulimia nervosa is unclear. PUBLIC SIGNIFICANCE: Atypical anorexia nervosa as described in the DSM-5 identifies individuals with many of the psychological characteristics of typical anorexia nervosa who, despite significant weight loss, are not underweight. The current systematic review found that the psychological symptoms and physiological characteristics of individuals with atypical AN are generally similar to those of individuals with AN, although there may be differences in the frequency of some physical complications.

OBJETIVO: En 2013 se realizó una descripción de la anorexia nerviosa atípica (ANA) en el DSM-5 y desde entonces se ha desarrollado una literatura considerable que describe las características clínicas de los individuos que padecen anorexia nerviosa atípica y los compara con los de los individuos que padecen anorexia nerviosa (AN) y los de individuos sanos. El propósito de este estudio fue realizar una revisión sistemática de esta literatura. MÉTODO: Se realizó una revisión sistemática siguiendo las guías PRISMA de estudios publicados desde 2013 que compararon las características clínicas de individuos que padecen anorexia nerviosa atípica con las de individuos que padecen anorexia nerviosa y/o controles sanos. Se realizaron metaanálisis cuando se reportaron medidas similares en tres o más estudios. RESULTADOS: Veinticuatro publicaciones cumplieron con los criterios de inclusión. Sus resultados indicaron que el nivel de psicopatología específica del trastorno de conducta alimentaria es significativamente mayor entre los individuos que padecen anorexia nerviosa atípica que entre los controles y tan alto o más alto como entre los individuos que padecen anorexia nerviosa, mientras que los niveles de psicopatología del no trastorno de la conducta alimentaria son similares. Los individuos que padecen anorexia nerviosa atípica experimentan muchas de las complicaciones fisiológicas asociadas con la anorexia nerviosa, pero algunas complicaciones parecen menos frecuentes. DISCUSIÓN: Los síntomas psicológicos y las complicaciones fisiológicas de los individuos que padecen anorexia nerviosa atípica son generalmente similares a los de los individuos que padecen anorexia nerviosa, aunque puede haber diferencias en la frecuencia de algunas complicaciones físicas. Hay poca información disponible sobre el curso, el resultado y la respuesta al tratamiento de los individuos que padecen AN atípica. Además, no se han desarrollado criterios diagnósticos completos para la anorexia nerviosa atípica, y la relación nosológica de la anorexia nerviosa atípica con los trastornos de la conducta alimentaria establecidos, como la bulimia nerviosa, no está clara.

Autonomic indices and loss-of-control eating in adolescents: an ecological momentary assessment study.

BACKGROUND: Loss-of-control (LOC) eating commonly develops during adolescence, and it predicts full-syndrome eating disorders and excess weight gain. Although negative emotions and emotion dysregulation are hypothesized to precede and predict LOC eating, they are rarely examined outside the self-report domain. Autonomic indices, including heart rate (HR) and heart rate variability (HRV), may provide information about stress and capacity for emotion regulation in response to stress. METHODS: We studied whether autonomic indices predict LOC eating in real-time in adolescents with LOC eating and body mass index (BMI) ⩾70th percentile. Twenty-four adolescents aged 12-18 (67% female; BMI percentile mean ± standard deviation = 92.6 ± 9.4) who reported at least twice-monthly LOC episodes wore biosensors to monitor HR, HRV, and physical activity for 1 week. They reported their degree of LOC after all eating episodes on a visual analog scale (0-100) using a smartphone. RESULTS: Adjusting for physical activity and time of day, higher HR and lower HRV predicted higher self-reported LOC after eating. Parsing between- and within-subjects effects, there was a significant, positive, within-subjects association between pre-meal HR and post-meal LOC rating. However, there was no significant within-subjects effect for HRV, nor were there between-subjects effects for either electrophysiologic variable. CONCLUSIONS: Findings suggest that autonomic indices may either be a marker of risk for subsequent LOC eating or contribute to LOC eating. Linking physiological markers with behavior in the natural environment can improve knowledge of illness mechanisms and provide new avenues for intervention.

Eating behavior in atypical anorexia nervosa.

OBJECTIVE: Atypical anorexia nervosa (AN) has been increasingly identified in the community and in clinical settings. Initial studies indicate that psychological symptoms are similar or more severe among patients with atypical AN, as compared with AN. This study examined whether eating behavior differed among patients with AN (n = 98), patients with atypical AN (n = 18), and healthy controls (HC, n = 75). METHOD: Adults and adolescents chose what to eat from a standardized, laboratory-based multi-item meal. Total intake, macronutrient composition, diet variety, and energy density were compared between groups. RESULTS: Both AN and atypical AN severely restricted caloric intake as compared with HC (431 ± 396 kcal and 340 ± 338 kcal vs. 879 ± 350 kcal, F2,188  = 35.4, p < .001). Individuals with AN and atypical AN did not differ in the mean intake of total calories or percentage of calories from fat (15.2 ± 25.2% vs. 11.5 ± 16.9%). DISCUSSION: This study demonstrates that individuals with atypical AN are at least as restrictive in their food intake as individuals with AN, and the restriction of dietary fat is particularly notable. Examination of eating behavior in a larger sample would be useful to replicate these findings. The current study highlights the need to understand maladaptive eating behavior in atypical AN in order to develop appropriate treatment recommendations. PUBLIC SIGNIFICANCE: Atypical anorexia nervosa is emerging as a prevalent eating disorder in community and clinical populations. The findings that patients with atypical anorexia nervosa limit calorie and fat intake in a pattern similar to that of patients with anorexia nervosa highlights the need for research to identify appropriate treatment strategies for normalization of eating patterns.

Early Course of Symptom Development in Anorexia Nervosa.

PURPOSE: Anorexia nervosa (AN) commonly begins in adolescence; however, detailed knowledge of symptom trajectories, including their temporal sequence, is less well elucidated. The purpose of the present study is to describe the onset and duration of disordered eating behaviors prior to a diagnosis of AN, examine concordance between child and parent report, and examine the relationships between timing of symptom onset and illness severity. METHODS: Seventy-one adolescents (ages 12-18 years) and their parents were interviewed about dieting, restriction, loss of control/binge eating, purging, excessive/compulsive exercise, weight history, and amenorrhea. Body mass index percentiles were calculated, and adolescents completed the Eating Disorder Examination-Questionnaire. RESULTS: Restriction, being underweight, dieting, and excessive exercise were reported by most of the sample; purging, loss-of-control eating, and having been overweight were reported by less than a third. Dieting typically emerged first, on average around age 14; the remainder of behaviors tended to emerge between ages 14 and 14½; and average age of formal diagnosis was slightly over 15 years. Dyads had good agreement regarding presence and timing of all behaviors except for dieting, for which children reported about 6 months earlier onset/longer duration, compared to parents. Although older age at interview was associated with lower body mass index percentile and higher EDE-Q score, neither age of onset nor duration was associated with severity when controlling for current age. DISCUSSION: Teens and parents describe a similar sequence of behavior changes leading up to a diagnosis of AN that typically begins with dieting and occurs over an approximate 1- to 1½-year period. Querying teens and parents about eating behavior changes may aid in identification and early intervention in AN; adolescents with normal weight who engage in persistent dieting or restrictive eating may warrant more frequent weight monitoring.

Eating Disorders.

Eating disorders are common behavioral disorders associated with substantial psychological and physical morbidity and mortality. Persons with eating disorders frequently present to primary care providers, who may also be responsible for their general medical management. This article reviews the diagnosis, medical assessment, and treatment of the most common eating disorders.

Optimizing relapse prevention and changing habits (REACH+) in anorexia nervosa.

INTRODUCTION: Relapse rates in anorexia nervosa (AN) are high, even after full weight restoration. This study aims to develop a relapse prevention treatment that specifically addresses persistent maladaptive behaviors (habits). Relapse Prevention and Changing Habits (REACH+) aims to support patients in developing routines that promote weight maintenance, encourage health, and challenge habits that perpetuate illness. The clinical trial design uses the Multiphase Optimization STrategy (MOST) framework to efficiently identify which components of treatment contribute to positive outcomes. METHODS: Participants will be 60 adults with AN who have achieved weight restoration in an inpatient setting. Treatment will consist of 6 months of outpatient telehealth sessions. REACH+ consists of behavior, cognitive, and motivation components, as well as food monitoring and a skill consolidation phase. A specialized online platform extends therapy between sessions. Participants will be randomly assigned to different versions of each component in a fractional factorial design. Outcomes will focus on maintenance of remission, measured by rate of weight loss and end-of-trial status. Interventions that contribute to remission will be included in an optimized treatment package, suitable for a large-scale clinical trial of relapse prevention in AN.

Neural Representations of Food-Related Attributes in the Human Orbitofrontal Cortex during Choice Deliberation in Anorexia Nervosa.

Decisions about what to eat recruit the orbitofrontal cortex (OFC) and involve the evaluation of food-related attributes such as taste and health. These attributes are used differently by healthy individuals and patients with disordered eating behavior, but it is unclear whether these attributes are decodable from activity in the OFC in both groups and whether neural representations of these attributes are differentially related to decisions about food. We used fMRI combined with behavioral tasks to investigate the representation of taste and health attributes in the human OFC and the role of these representations in food choices in healthy women and women with anorexia nervosa (AN). We found that subjective ratings of tastiness and healthiness could be decoded from patterns of activity in the OFC in both groups. However, health-related patterns of activity in the OFC were more related to the magnitude of choice preferences among patients with AN than healthy individuals. These findings suggest that maladaptive decision-making in AN is associated with more consideration of health information represented by the OFC during deliberation about what to eat.SIGNIFICANCE STATEMENT An open question about the OFC is whether it supports the evaluation of food-related attributes during deliberation about what to eat. We found that healthiness and tastiness information was decodable from patterns of neural activity in the OFC in both patients with AN and healthy controls. Critically, neural representations of health were more strongly related to choices in patients with AN, suggesting that maladaptive overconsideration of healthiness during deliberation about what to eat is related to activity in the OFC. More broadly, these results show that activity in the human OFC is associated with the evaluation of relevant attributes during value-based decision-making. These findings may also guide future research into the development of treatments for AN.

Restrictive eating across a spectrum from healthy to unhealthy: behavioral and neural mechanisms.

BACKGROUND: Restriction of food intake is a central feature of anorexia nervosa (AN) and other eating disorders, yet also occurs in the absence of psychopathology. The neural mechanisms of restrictive eating in health and disease are unclear. METHODS: This study examined behavioral and neural mechanisms associated with restrictive eating among individuals with and without eating disorders. Dietary restriction was examined in four groups of women (n = 110): healthy controls, dieting healthy controls, patients with subthreshold (non-low weight) AN, and patients with AN. A Food Choice Task was administered during fMRI scanning to examine neural activation associated with food choices, and a laboratory meal was conducted. RESULTS: Behavioral findings distinguished between healthy and ill participants. Healthy individuals, both dieting and non-dieting, chose significantly more high-fat foods than patients with AN or subthreshold AN. Among healthy individuals, choice was primarily influenced by tastiness, whereas, among both patient groups, healthiness played a larger role. Dorsal striatal activation associated with choice was most pronounced among individuals with AN and was significantly associated with selecting fewer high-fat choices in the task and lower caloric intake in the meal the following day. CONCLUSIONS: A continuous spectrum of behavior was suggested by the increasing amount of weight loss across groups. Yet, data from this Food Choice Task with fMRI suggest there is a behavioral distinction between illness and health, and that the neural mechanisms underlying food choice in AN are distinct. These behavioral and neural mechanisms of restrictive eating may be useful targets for treatment development.

Open science practices for eating disorders research.

This editorial seeks to encourage the increased application of three open science practices in eating disorders research: Preregistration, Registered Reports, and the sharing of materials, data, and code. For each of these practices, we introduce updated International Journal of Eating Disorders author and reviewer guidance. Updates include the introduction of open science badges; specific instructions about how to improve transparency; and the introduction of Registered Reports of systematic or meta-analytical reviews. The editorial also seeks to encourage the study of open science practices. Open science practices pose considerable time and other resource burdens. Therefore, research is needed to help determine the value of these added burdens and to identify efficient strategies for implementing open science practices.

Associations between mealtime anxiety and food intake in anorexia nervosa.

OBJECTIVE: A salient disturbance in anorexia nervosa (AN) is the persistent restriction of food intake. Eating behavior in AN is thought to be influenced by anxiety. The current study probed associations between mealtime anxiety and food intake among individuals with AN and healthy comparison individuals (HC). METHOD: Data were combined across three studies (total of 92 AN and 78 HC) for secondary data analysis. Participants completed a multiitem laboratory buffet meal and visual analogue scale assessments of pre-meal and post-meal anxiety. Linear regression models assessed the association between mealtime anxiety and calorie and fat intake at the meal, and whether associations differed by diagnostic group. RESULTS: Among individuals with AN, pre-meal anxiety was significantly associated with reduced calorie intake and reduced consumption of calories from fat at the meal; these associations were not observed among HC. There was no evidence for an association between calorie/fat intake at the meal and post-meal anxiety in either group. DISCUSSION: Treatments that target mealtime anxiety may improve eating and nourishment among individuals with AN. Interventions like exposure therapy that provide skills in overcoming mealtime anxiety might be enhanced by informing patients that post-meal anxiety is not related to intake.

Time Course of Relapse Following Acute Treatment for Anorexia Nervosa.

OBJECTIVE: There is long-standing interest in how best to define stages of illness for anorexia nervosa, including remission and recovery. The authors used data from a previously published study to examine the time course of relapse over the year following full weight restoration. METHODS: Following weight restoration in an acute care setting, 93 women with anorexia nervosa were randomly assigned to receive fluoxetine or placebo and were discharged to outpatient care, where they also received cognitive-behavioral therapy for up to 1 year. Relapse was defined on the basis of a priori clinical criteria. Fluoxetine had no impact on the time to relapse. In the present analysis, for each day after entry into the study, the risk of relapse over the following 60 days and the following 90 days was calculated and a parametric function was fitted to approximate the Kaplan-Meier estimator. RESULTS: The risk of relapse rose immediately after entry into the study, reached a peak after approximately 60 days, and then gradually declined. There was no indication of an inflection point at which the risk of relapse fell precipitously after the initial peak. CONCLUSIONS: This analysis highlights the fact that adult patients with anorexia nervosa are at increased risk of relapse in the first months following discharge from acute care, suggesting a need for frequent follow-up and relapse prevention-focused treatment during this period. After approximately 2 months, the risk of relapse progressively decreases over time.

Changes in brain and behavior during food-based decision-making following treatment of anorexia nervosa.

BACKGROUND: Anorexia nervosa is a severe illness with a high mortality rate, driven in large part by severe and persistent restriction of food intake. A critical challenge is to identify brain mechanisms associated with maladaptive eating behavior and whether they change with treatment. This study tested whether food choice-related caudate activation in anorexia nervosa changes with treatment. METHODS: Healthy women (n = 29) and women hospitalized with anorexia nervosa (n = 24), ages 18 to 40 years, completed a Food Choice Task during fMRI scanning at two timepoints. Among patients, procedures occurred upon hospital admission (Time 1) and again after patients had gained to normal weight (Time 2). Healthy controls were tested twice at an interval group-matched to patients. Choice-related caudate activation was assessed at each timepoint, using parametric analyses in an a priori region of interest. RESULTS: Among patients, the proportion of high-fat foods selected did not change over time (p's > 0.47), but decreased neural activity in the caudate after treatment was associated with increased selection of high-fat foods (r23 = - 0.43, p = 0.037). Choice-related caudate activation differed among women with anorexia nervosa vs healthy control women at Time 1 (healthy control: M = 0.15 ± 0.87, anorexia nervosa: M = 0.70 ± 1.1, t51 = - 2.05, p = 0.045), but not at Time 2 (healthy control: M = 0.18 ± 1.0, anorexia nervosa: M = 0.37 ± 0.99, t51 = - 0.694, p = 0.49). CONCLUSIONS: Caudate activity was more strongly associated with decisions about food among individuals with anorexia nervosa relative to healthy comparison individuals prior to treatment, and decreases in caudate engagement among individuals with anorexia nervosa undergoing treatment were associated with increases in high-fat food choices. The findings underscore the need for treatment development that more successfully alters both eating behavior and the neural mechanisms that guide it.

The association between leptin and weight maintenance outcome in anorexia nervosa.

OBJECTIVE: Relapse after weight restoration in anorexia nervosa (AN) is a critical problem. Higher body fat percentage after weight gain has been shown to predict better weight maintenance outcome. Leptin, a fat-derived hormone, has been associated with progress during weight gain, but its association with weight maintenance is unknown. This study aims to determine whether leptin levels after weight restoration in AN are associated with weight maintenance. METHOD: Participants were 41 women with AN hospitalized for inpatient treatment. Participants were evaluated 2-4 weeks after weight restoration to body mass index (BMI) ≥ 19.5 kg/m2 for plasma leptin and body composition. Weight maintenance outcome was defined by whether a participant maintained a BMI of at least 18.5 kg/m2 at the end of 1 year following hospital discharge. RESULTS: Twenty (48.8%) out of 41 patients maintained their weight at 1 year. Percent body fat and leptin were significantly higher in the group who maintained weight (body fat, p = .004, Hedges' g = 0.944; log-leptin, p = .010, Hedges' g = 0.821), but there were no differences in predischarge BMI, duration of illness, and duration of amenorrhea. Using regression modeling, only higher log-leptin (pWald = .021) and percent body fat (pWald = .010), as well as fat-adjusted leptin (pWald = .029), independently predicted weight maintenance at 1 year. DISCUSSIONS: Our findings suggest that for acutely-weight restored women with AN, higher predischarge leptin measurements are associated with better outcome in the year following treatment. Prospective studies examining leptin as well as other parameters of metabolic health could offer insights into biomarkers that may improve clinical outcomes.

Deficient Goal-Directed Control in a Population Characterized by Extreme Goal Pursuit.

Research in computational psychiatry has sought to understand the basis of compulsive behavior by relating it to basic psychological and neural mechanisms: specifically, goal-directed versus habitual control. These psychological categories have been further identified with formal computational algorithms, model-based and model-free learning, which helps to provide quantitative tools to distinguish them. Computational psychiatry may be particularly useful for examining phenomena in individuals with anorexia nervosa (AN), whose self-starvation appears both excessively goal directed and habitual. However, these laboratory-based studies have not aimed to examine complex behavior, as seen outside the laboratory, in contexts that extend beyond monetary rewards. We therefore assessed (1) whether behavior in AN was characterized by enhanced or diminished model-based behavior, (2) the domain specificity of any abnormalities by comparing learning in a food-specific (i.e., illness-relevant) context as well as in a monetary context, and (3) whether impairments were secondary to starvation by comparing learning before and after initial treatment. Across all conditions, individuals with AN, relative to healthy controls, showed an impairment in model-based, but not model-free, learning, suggesting a general and persistent contribution of habitual over goal-directed control, across domains and time points. Thus, eating behavior in individuals with AN that appears very goal-directed may be under more habitual than goal-directed control, and this is not remediated by achieving weight restoration.