State-specific alterations in the neural computations underlying inhibitory control in women remitted from bulimia nervosa.

The neurocomputational processes underlying bulimia nervosa and its primary symptoms, out-of-control overeating and purging, are poorly understood. Research suggests that the brains of healthy individuals form a dynamic internal model to predict whether control is needed in each moment. This study tested the hypothesis that this computational process of inhibitory control is abnormally affected by metabolic state (being fasted or fed) in bulimia nervosa.

Satiety does not alter the ventral striatum's response to immediate reward in bulimia nervosa.

Individuals with bulimia nervosa (BN) cycle between periods of binge-eating and compensatory behavior and periods of dietary restraint, suggesting extremes of under and overcontrol that may be metabolic-state related. This study examined the influence of hunger and satiety on impulsivity and neural responding during decision-making. Twenty-three women remitted from BN (RBN) and 20 healthy comparison women (CW) performed a delay discounting task after a 16-hr fast and following a standardized meal during functional neuroimaging.

Neural Insensitivity to the Effects of Hunger in Women Remitted From Anorexia Nervosa.

Objective: Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa.

Altered anticipation and processing of aversive interoceptive experience among women remitted from bulimia nervosa.

Bulimia nervosa (BN) is characterized by dysregulated intake of food, which may indicate homeostatic imbalance. Critically important for homeostatic regulation is interoception, or the sensing and processing of body-relevant information. A well-documented link between avoidance of unpleasant body sensations and BN symptoms suggests that aversive interoceptive experiences may be particularly relevant to BN pathophysiology.

A pilot open series of lamotrigine in DBT-treated eating disorders characterized by significant affective dysregulation and poor impulse control.

Background: There is little effective psychopharmacological treatment for individuals with eating disorders who struggle with pervasive, severe affective and behavioral dysregulation.

Methods: This pilot open series evaluated lamotrigine, a mood stabilizer, in the treatment of patients with eating disorders who did not respond adequately to antidepressant medications. Nine women with anorexia nervosa- or bulimia nervosa-spectrum eating disorders in partial hospital or intensive outpatient dialectical behavior therapy (DBT)-based eating disorder treatment took lamotrigine for 147 ± 79 days (mean final dose = 161.

Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa.

The etiology of pathological eating in anorexia nervosa (AN) remains poorly understood. Cerebral blood flow (CBF) is an indirect marker of neuronal function. In healthy adults, fasting increases CBF, reflecting increased delivery of oxygen and glucose to support brain metabolism.

Response in taste circuitry is not modulated by hunger and satiety in women remitted from bulimia nervosa.

Individuals with bulimia nervosa (BN) engage in episodes of binge eating, marked by loss of control and eating despite fullness. Does altered reward and metabolic state contribute to BN pathophysiology? Normally, hunger increases (and satiety decreases) reward salience to regulate eating. We investigated whether BN is associated with an abnormal response in a neural circuit involved in translating taste signals into motivated behavior, when hungry and fed.

Dopaminergic activity and altered reward modulation in anorexia nervosa-insight from multimodal imaging.

Objective: Individuals with anorexia nervosa (AN) have anxious and inhibited temperaments with high concern for consequences. Studies using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI) suggest involvement of the middle and dorsal caudate (DC) in individuals recovered (REC) from AN. For example, dopamine (DA) D2/D3 receptor binding in the middle caudate and DC was associated with anxiety and harm avoidance, and blood-oxygen-level-dependent (BOLD) response in the DC was positively related to trait anxiety.

Are Extremes of Consumption in Eating Disorders Related to an Altered Balance between Reward and Inhibition?

The primary defining characteristic of a diagnosis of an eating disorder (ED) is the "disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food" (DSM V; American Psychiatric Association, 2013). There is a spectrum, ranging from those who severely restrict eating and become emaciated on one end to those who binge and overconsume, usually accompanied by some form of compensatory behaviors, on the other. How can we understand reasons for such extremes of food consummatory behaviors? Recent work on obesity and substance use disorders has identified behaviors and neural pathways that play a powerful role in human consummatory behaviors.

Hunger does not motivate reward in women remitted from anorexia nervosa.

Background: Hunger enhances sensitivity to reward, yet individuals with anorexia nervosa (AN) are not motivated to eat when starved. This study investigated brain response to rewards during hunger and satiated states to examine whether diminished response to reward could underlie food restriction in AN.

Methods: Using a delay discounting monetary decision task known to discriminate brain regions contributing to processing of immediate rewards and cognitive control important for decision making regarding future rewards, we compared 23 women remitted from AN (RAN group; to reduce the confounding effects of starvation) with 17 healthy comparison women (CW group).

Does a shared neurobiology for foods and drugs of abuse contribute to extremes of food ingestion in anorexia and bulimia nervosa?

Is starvation in anorexia nervosa (AN) or overeating in bulimia nervosa (BN) a form of addiction? Alternatively, why are individuals with BN more vulnerable and individuals with AN protected from substance abuse? Such questions have been generated by recent studies suggesting that there are overlapping neural circuits for foods and drugs of abuse. To determine whether a shared neurobiology contributes to eating disorders and substance abuse, this review focused on imaging studies that investigated response to tastes of food and tasks designed to characterize reward and behavioral inhibition in AN and BN. BN and those with substance abuse disorders may share dopamine D2 receptor-related vulnerabilities, and opposite findings may contribute to "protection" from substance abuse in AN.

Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa.

Individuals with anorexia nervosa (AN) engage in relentless restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN.

Interaction between serotonin transporter and dopamine D2/D3 receptor radioligand measures is associated with harm avoidant symptoms in anorexia and bulimia nervosa.

Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have alterations of measures of serotonin (5-HT) and dopamine (DA) function, which persist after long-term recovery and are associated with elevated harm avoidance (HA), a measure of anxiety and behavioral inhibition. Based on theories that 5-HT is an aversive motivational system that may oppose a DA-related appetitive system, we explored interactions of positron emission tomography (PET) radioligand measures that reflect portions of these systems. Twenty-seven individuals recovered (REC) from eating disorders (EDs) (7 AN-BN, 11 AN, 9 BN) and nine control women (CW) were analyzed for correlations between [(11)C]McN5652 and [(11)C]raclopride binding.

Amphetamine induced dopamine release increases anxiety in individuals recovered from anorexia nervosa.

Objective: Genetic, pharmacologic, and physiological data suggest that individuals with anorexia nervosa (AN) have altered striatal dopamine (DA) function.

Method: We used an amphetamine challenge and positron emission tomography [(11) C]raclopride paradigm to explore DA striatal transmission in 10 recovered (REC) AN compared with 9 control women (CW).

Results: REC AN and CW were similar for baseline, postamphetamine [(11) C]raclopride binding potential (BP(ND) ) and change (Δ) in BP(ND) for all regions.

Serotonin: imaging findings in eating disorders.

Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by aberrant patterns of feeding behavior, weight regulation, and disturbances in attitudes and perceptions toward body weight and shape. Several lines of evidence nominate disturbances of serotonin (5-HT) pathways as playing a role in the pathogenesis and pathophysiology of AN and BN. For example, 5-HT pathways are known to contribute to the modulation of a range of behaviors commonly seen in individuals with AN and BN.

5-HT₁A receptor binding is increased after recovery from bulimia nervosa compared to control women and is associated with behavioral inhibition in both groups.

Objective: Because altered serotonin (5-HT) function appears to persist after recovery from bulimia nervosa (RBN), we investigated the 5-HT(1A) receptor, which could contribute to regulation of appetite, mood, impulse control, or the response to antidepressants.

Method: Thirteen RBN individuals were compared to 21 healthy control women (CW) using positron emission tomography and [carbonyl-(11)C]WAY100635 ([(11)C]WAY).

Results: RBN had a 23-34% elevation of [(11)C]WAY binding potential (BP)(P) in subgenual cingulate, mesial temporal, and parietal regions after adjustments for multiple comparisons.

Altered striatal response to reward in bulimia nervosa after recovery.

Objective: It is possible that disturbances of systems modulating reward may contribute to a vulnerability to develop an eating disorder.

Method: This hypothesis was tested by assessing functional magnetic resonance brain imaging response to a monetary reward task known to activate the anterior ventral striatum (AVS), a region implicated in motivational aspects toward stimuli. To avoid the confounding effects of malnutrition, 10 women who had recovered from bulimia nervosa (BN) were compared with 10 healthy comparison women (CW).

Altered reward processing in women recovered from anorexia nervosa.

Objective: Individuals with anorexia nervosa are known to be ascetic and able to sustain self-denial of food as well as most comforts and pleasures in life. Building on previous findings of altered striatal dopamine binding in anorexia nervosa, the authors sought to assess the response of the anterior ventral striatum to reward and loss in this disorder.

Method: Striatal responses to a simple monetary reward task were investigated using event-related functional magnetic resonance imaging.

Serotonin transporter binding after recovery from eating disorders.

Rationale: Several lines of evidence suggest that altered serotonin (5-HT) function persists after recovery from anorexia nervosa (AN) and bulimia nervosa (BN).

Objectives: We compared 11 subjects who recovered (>1 year normal weight, regular menstrual cycles, no binging or purging) from restricting-type AN (REC RAN), 7 who recovered from bulimia-type AN (REC BAN), 9 who recovered from BN (REC BN), and 10 healthy control women (CW).

Materials And Methods: Positron emission tomography (PET) imaging with [11C]McN5652 was used to assess the 5-HT transporter (5-HTT).

Regional cerebral blood flow after recovery from anorexia or bulimia nervosa.

Objective: Abnormalities of regional cerebral blood flow (rCBF) have been found in individuals who are ill with anorexia (AN) or bulimia nervosa (BN). Little is known about whether rCBF normalizes after recovery from AN and BN.

Method: Eighteen control women (CW), 10 recovered restricting type AN, 8 recovered AN with a binging history, and 9 recovered BN participants without a history of AN were studied using positron emission tomography and [(15)O]water in order to assess rCBF.

Altered insula response to taste stimuli in individuals recovered from restricting-type anorexia nervosa.

Anorexia nervosa (AN) is an illness characterized by aversion to ingestion of normally palatable foods. We examined whether there is a primary disturbance of taste processing and experience of pleasure using a sucrose/water task in conjunction with functional magnetic resonance imaging (fMRI). To avoid confounding effects of illness, 16 women recovered from restricting-type AN were compared to 16 control women (CW).

Exaggerated 5-HT1A but normal 5-HT2A receptor activity in individuals ill with anorexia nervosa.

Background: Many studies have found disturbances of serotonin (5-HT) activity in anorexia nervosa (AN). Because little is known about 5-HT receptor function in AN, positron emission tomography (PET) imaging with 5-HT receptor-specific radioligands was used to characterize 5-HT1A and 5-HT2A receptors.

Methods: Fifteen women ill with AN (ILL AN) were compared with 29 healthy control women (CW); PET and [11C]WAY100635 were used to assess binding potential (BP) of the 5-HT1A receptor, and [18F]altanserin was used to assess postsynaptic 5-HT2A receptor BP.

Neural correlates of habituation to taste stimuli in healthy women.

Recent studies show that specific regions of the cortex contribute to modulation of appetitive behaviors. The purpose of this study was to determine whether neural response in these regions changes over time when a taste stimulus is administered repeatedly. Such a paradigm may be useful for determining whether altered habituation contributes to disturbed eating behavior.

Personality traits after recovery from eating disorders: do subtypes differ?

Objective: We compared individuals recovered from anorexia (AN) and bulimia nervosa (BN) to determine characteristics that are shared by or distinguish eating disorder (ED) subtypes.

Method: Sixty women recovered for > or = 1 year from AN or BN were compared with 47 control women (CW). Assessments included the Yale-Brown-Cornell Eating Disorder Scale, the Spielberger State-Trait Anxiety Inventory, the Beck Depression Inventory, the Yale-Brown Obsessive Compulsive Scale, the Temperament and Character Inventory, and Structured Clinical Interviews for DSM-IV.