Angela Wagner

Increased Dopamine D2/D3 Receptor Binding After Recovery from Anorexia Nervosa Measured by Positron Emission Tomography and [11C]Raclopride

BACKGROUND Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). METHODS To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [(11)C]raclopride was used to assess DA D2/D3 receptor binding. RESULTS The women who were recovered from AN had significantly higher [(11)C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. CONCLUSIONS These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.

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). We used a region of interest-based fMRI approach to test the idea that individuals with AN have differential neural activation in primary and secondary taste cortical regions after sucrose and water administration. Compared to CW, individuals recovered from AN showed a significantly lower neural activation of the insula, including the primary cortical taste region, and ventral and dorsal striatum to both sucrose and water. In addition, insular neural activity correlated with pleasantness ratings for sucrose in CW, but not in AN subjects. Altered taste processing may occur in AN, based on differences in activity in insular–striatal circuits. These data provide the first evidence that individuals with AN process taste stimuli differently than controls, based on differences in neural activation patterns.

Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging studies.

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with relatively homogenous presentations such as age of onset and gender distribution. In addition, they share symptoms, such as extremes of food consumption, body image distortion, anxiety and obsessions, and ego-syntonic neglect, raises the possibility that these symptoms reflect disturbed brain function that contributes to the pathophysiology of this illness. Recent brain imaging studies have identified altered activity in frontal, cingulate, temporal, and parietal cortical regions in AN and BN. Importantly, such disturbances are present when subjects are ill and persist after recovery, suggesting that these may be traits that are independent of the state of the illness. Emerging data point to a dysregulation of serotonin pathways in cortical and limbic structures that may be related to anxiety, behavioral inhibition, and body image distortions. In specific, recent studies using PET with serotonin specific radioligands implicate alterations of 5-HT1A and 5-HT2A receptors and the 5-HT transporter. Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.

Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa.

BACKGROUND Individuals who are ill with anorexia (AN) and bulimia nervosa (BN) often have increased cerebrospinal fluid (CSF) volumes and decreased total gray and white matter volumes. It is unclear whether such disturbances persist after recovery from an eating disorder. METHODS Magnetic resonance imaging was performed on 40 women who were long-term recovered (>1 year no binging, purging, or restricting behaviors, normal weight, and menstrual cycles, not on medication) from restricting or binge/purging type AN or BN and 31 healthy control women (CW). Voxel-based morphometry (VBM) was used for data analysis. RESULTS Recovered AN and BN subgroups were similar to CW in terms of cerebrospinal fluid (CSF) volume as well as total or regional gray or white matter volume. CONCLUSIONS These findings suggest that structural brain abnormalities are reversible in individuals with eating disorders after long-term recovery.

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. [15O] water and PET were used to assess cerebral blood flow. RESULTS The ILL AN women had a highly significant (30%-70%) increase in [11C]WAY100635 BP in prefrontal and lateral orbital frontal regions, mesial and lateral temporal lobes, parietal cortex, and dorsal raphe nuclei compared with CW. The [18F]altanserin BP was normal in ILL AN but was positively and significantly related to harm avoidance in suprapragenual cingulate, frontal, and parietal regions. Cerebral blood flow was normal in ILL AN women. CONCLUSIONS Increased activity of 5-HT1A receptor activity may help explain poor response to 5-HT medication in ILL AN. This study extends data suggesting that 5-HT function, and, specifically, the 5-HT2A receptor, is related to anxiety in AN.

Altered Insula Response to Sweet Taste Processing After Recovery From Anorexia and Bulimia Nervosa

OBJECTIVE Recent studies suggest that altered function of higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa and overeating in bulimia nervosa. This study used sweet tastes to interrogate gustatory neurocircuitry involving the anterior insula and related regions that modulate sensory-interoceptive-reward signals in response to palatable foods. METHOD Participants who had recovered from anorexia nervosa and bulimia nervosa were studied to avoid confounding effects of altered nutritional state. Functional MRI measured brain response to repeated tastes of sucrose and sucralose to disentangle neural processing of caloric and noncaloric sweet tastes. Whole-brain functional analysis was constrained to anatomical regions of interest. RESULTS Relative to matched comparison women (N=14), women recovered from anorexia nervosa (N=14) had significantly diminished and women recovered from bulimia nervosa (N=14) had significantly elevated hemodynamic response to tastes of sucrose in the right anterior insula. Anterior insula response to sucrose compared with sucralose was exaggerated in the recovered group (lower in women recovered from anorexia nervosa and higher in women recovered from bulimia nervosa). CONCLUSIONS The anterior insula integrates sensory reward aspects of taste in the service of nutritional homeostasis. One possibility is that restricted eating and weight loss occur in anorexia nervosa because of a failure to accurately recognize hunger signals, whereas overeating in bulimia nervosa could represent an exaggerated perception of hunger signals. This response may reflect the altered calibration of signals related to sweet taste and the caloric content of food and may offer a pathway to novel and more effective treatments.

Neuroimaging Studies in Eating Disorders

The understanding of the eating disorders (EDs) anorexia (AN) and bulimia nervosa (BN) has undergone remarkable advancements in the past decade. Most studies that have been done in AN show brain gray and white matter volume loss during the ill state that, at least in part, remit with recovery. Similar patterns occur for brain phospholipids assessed using magnet resonance spectroscopy (MRS). Imaging studies have been used to provide functional information regarding serotonin neuroreceptor dynamics, regional cerebral blood flow, or cerebral glucose metabolism. Such studies have implicated cingulate, frontal, temporal, and parietal regions in AN. Investigators have found that challenges such as food and body image distortions may activate some of these regions, raising the possibility that such studies may shed light on puzzling AN symptoms, such as body image distortions or extremes of appetitive behaviors. Emerging data suggest these disturbances persist after recovery from AN, suggesting the possibility that these are traits that may create a vulnerability to develop an ED. While fewer studies have been done in BN or binge eating disorder, there may be disturbances of serotonin metabolism in similar brain regions. Taken together, these findings give promise for future investigations with the hope of delineating brain pathways that contribute to the etiology of EDs

Neurocircuity of Eating Disorders

OBJECTIVES This chapter reviews brain imaging findings in anorexia and bulimia nervosa which characterize brain circuitry that may contribute to the pathophysiology of eating disorders (EDs). SUMMARY OF RECENT FINDINGS Recent imaging studies provide evidence of disturbed gustatory processing in EDs which involve the anterior insula as well as striatal regions. These results raise the possibility that individuals with anorexia nervosa have altered appetitive mechanism that may involve sensory, interoceptive, or reward processes. Furthermore, evidence of altered reward mechanisms is supported by studies that suggest that individuals with anorexia nervosa and bulimia nervosa share a trait toward similar anterior ventral striatal pathway dysregulation. This shared trait disturbance of the modulation of reward and emotionality may create a vulnerability for dysregulated appetitive behaviors. However, those with anorexia nervosa may be able to inhibit appetite and have extraordinary self-control because of exaggerated dorsal cognitive circuit function, whereas individuals with bulimia nervosa are vulnerable to overeating when they get hungry, because they have less ability to control their impulses. FUTURE DIRECTIONS Current therapeutic interventions have modest success. Better understanding of neurocircuits that may be related to altered appetite, mood, impulse control, and other symptoms underlying the pathophysiology of EDs might improve psychotherapeutic and drug treatment strategies.

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). RESULTS For the AVS, CW distinguished positive and negative feedback, whereas recovered BN women had similar responses to both conditions. In addition, these groups had similar patterns of findings for the dorsal caudate. DISCUSSION We have previously shown that individuals recovered from anorexia nervosa (AN) also had altered striatal responses and difficulties in differentiating positive and negative feedback. Thus BN and AN individuals may share a difficulty in discriminating the emotional significance of a stimulus.

Brain imaging of serotonin after recovery from anorexia and bulimia nervosa

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with relatively homogenous presentations such as age of onset and gender distribution. In addition, they share symptoms, such as extremes of food consumption, body image distortion, anxiety and obsessions, and ego-syntonic neglect. Taken together, these observations raise the possibility that these symptoms reflect disturbed brain function, which contributes to the pathophysiology of these illnesses. Several lines of evidence suggest that disturbances of serotonin (5-HT) pathways play a role. First, 5-HT pathways contribute to the modulation of feeding, mood, and impulse control. Second, medications that act on 5-HT pathways have some degree of efficacy in individuals with AN and BN. Third, such disturbances are present when subjects are ill and persist after recovery, suggesting that 5-HT alterations may be traits that are independent of the state of the illness. Positron emission tomography (PET) with radioligands offers an opportunity to directly characterize brain 5-HT pathways and their relationship with behavior. For example, reduced 5-HT(2A) receptor function occurs in AN whereas increased 5-HT(1A) receptor function occurs in BN. Moreover, imaging studies correlate altered 5-HT(1A) and 5-HT(2A) receptor function with traits often found in individuals with AN and BN, such as harm avoidance. Finally, alteration of these receptors tends to implicate pathways involving frontal, cingulate, temporal, and parietal regions. Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.