Annual Review of Eating Disorders

2006, Pt. 2

Stephen Wonderlich, James Mitchell, Liz Boath, Howard Steiger, Scott Crow

• Publisher: Taylor & Francis
• Year: 2018
• eBook ISBN: 9781315347677
• Edition: 1
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

This book contains reviews from leading scientists and clinicians drawing together the latest developments in the ten key topics covering the major areas of eating disorders including bulimia, body image, socio-cultural issues and anorexia. This volume compliments "Annual Review of Eating Disorders Part 1". Together, the two books cover the twenty main topics identified by the Academy of Eating Disorders as providing essential knowledge in the field. It is ideal for busy clinicians, with a clear emphasis on clinical implications and is supported by the American Academy for Eating Disorders. Clinicians and health researchers involved in the area of eating disorders will find this review invaluable, as will professional organisations for psychologists, psychiatrists, dieticians, general practitioners, paediatricians, counsellors and educators.

1
Psychobiology of eating disorders

David C Jimerson and Barbara E Wolfe

Abstract

Objectives of review. The goal of this review is to highlight selected advances during 2003-2004 in research on the psychobiology of the eating disorders.

Summary of recent findings. Studies in bulimia nervosa (BN) have demonstrated associations between alterations in serotonin function and comorbid psychiatric disorders, while studies in both BN and anorexia nervosa (AN) have provided additional evidence for persistent, possibly trait-related alterations in serotonin regulation. Studies of leptin function have shown an association between circulating levels of the protein and symptom patterns during the course of recovery from AN. Studies of ghrelin function have provided new evidence for altered postprandial release of the peptide in BN and binge-eating disorder, and elevated baseline levels of the peptide in AN.

Future directions. Additional research will be needed to assess both categorical and dimensional clinical correlates of alterations in these neuro-biological systems. Studies in individuals who have recovered from the eating disorders will be valuable in identifying stable psychobiological characteristics. Future results may lead to new pharmacological treatment approaches.

Introduction

A variety of factors have contributed to the rapid acceleration of research on the psychobiology of eating disorders. Preclinical advances in molecular and behavioral neurobiology have led to increased understanding of the regulation of neurotransmitters, neuropeptides, neurohormones and other neuromodulators acting in the hypothalamus and cortical brain regions to regulate food intake, mood, stress response and cognition. Preclinical and clinical investigations related to obesity and energy metabolism have led to increased understanding of the important role of peripheral signals, particularly involving gut peptides and adipokines, in influencing central nervous system (CNS) processes regulating energy metabolism and eating patterns. New technologies for clinical investigation, including functional imaging and genetics, have also accelerated the pace of research. Finally, there has been increased refinement of diagnostic criteria and more detailed understanding of symptom patterns associated with the eating disorders.

The current review focuses selectively on the neurotransmitter serotonin, the adipokine leptin, and the gut-related peptide ghrelin. These neurobiological messengers appear likely to play an important role in our understanding of the eating disorders, and have been the focus of intensive study during the period of 2003 to 2004 covered by the review. Within each section, we provide a brief overview of studies through 2002, and a more focused outline of new research during the review period. Related aspects of research advances, particularly with regard to serotonin function, are reviewed in the chapters on ‘Review of brain imaging in anorexia and bulimia nervosa’ and ‘Genetics of eating disorders’.

Literature review

Serotonin

Interest in the possible role of abnormal serotonin regulation in the eating disorders has been driven by preclinical studies showing that serotonin plays an important role in regulating meal patterns; by clinical studies associating serotonin with symptoms of depression, impulsivity and obsessive-compulsive behavioral patterns; and by research indicating that therapeutic effects of antidepressant medications are associated with augmentation of synaptic serotonin function (Wolfe et al. 1997). Of particular interest are recent studies showing that serotonin interacts with other neurotransmitters and neuropeptides in the hypothalamus to regulate eating behavior (Heisler et al. 2003).

Serotonin function in bulimia nervosa

As previously reviewed (Wolfe et al. 1997; Kaye et al. 2004), BN appears to be associated with a decrease in CNS serotonin function. Thus, in comparison to healthy controls, patients with BN have decreased concentration of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), and blunted neuroendocrine responses to serotonin agonist drugs such as m-chlorophenylpiperazine (mCPP) or fenfluramine. Other evidence for altered serotonin regulation in BN emerged from studies of acute tryptophan depletion (Kaye et al. 2000) and platelet antidepressant (e.g. [³H]-paroxetine) binding (Steiger et al. 2001a).

Several groups have explored the relationship between binge-eating behavior, comorbid psychiatric symptomatology and serotonergic responsiveness. In CSF metabolite and neuroendocrine studies, patients with the highest severity of bulimic symptoms have shown the most prominent deficit in serotonergic responses (Jimerson et al. 1997; Monteleone et al. 2000). In a series of studies, Steiger and colleagues reported that alterations in serotonergic neuroendocrine and platelet measures in patients with BN appeared to be associated with a range of behavioral characteristics (Steiger 2004), including childhood abuse (Steiger et al. 2004), self-destructiveness (Steiger et al. 2001b), impulsivity (Steiger et al. 2003) and avoidant personality (Bruce et al. 2004). Another recent study found that platelet paroxetine binding was altered in patients with AN or BN, although the platelet measures did not appear to be correlated with symptom severity, impulsivity or depression (Ramacciotti et al. 2003). Relatively small samples for BN in the latter study may, however, have provided limited power for detecting associations between neurobiological and symptom indices. In addition, the effects of severe malnutrition in patients with AN may limit the ability to detect underlying associations between peripheral neurobiological indices and behavioral traits.

Functional imaging studies using single-photon emission computed tomography (SPECT) or positron emission tomography (PET) in BN have shown, in comparison to controls, regional decreases in brain serotonin transporter availability (Tauscher et al. 2001) and increases in 5-HT_1A receptor binding (Tiihonen et al. 2004), but no apparent alteration in binding to the 5HT_2A receptor (Goethals et al. 2004).

There has been considerable interest in whether or not there are trait-related alterations in serotonin function in individuals with a history of BN following remission of abnormal eating patterns. Findings to date indicate that recovered individuals have elevated levels of CSF 5-HIAA, increased sensitivity to reduction of serotonin synthesis following acute tryptophan depletion, and regional decreases in 5-HT_2A binding, but apparently normal neuroendocrine responses (Kaye et al. 1998; Smith et al. 1999; Wolfe et al. 2000; Kaye et al. 2001).

Serotonin function in binge-eating disorder

An initial study reported normal neuroendocrine responses to a serotonin agonist drug in patients with this disorder (Monteleone et al. 2000). Of interest, obese patients with binge eating were shown to have reduced serotonin transporter binding (as measured by SPECT) in comparison to obese controls (Kuikka et al. 2001). Transporter binding was found to increase in symptomat-ically recovered patients (Tammela et al. 2003).

Serotonin function in anorexia nervosa

Studies in AN have consistently shown reduced serotonin function, as reflected in significant reduction of 5-HIAA concentration in CSF and diminished neuroendocrine response to serotonergic agonist drugs (Brewerton and Jimerson 1996; Wolfe et al. 1997; Kaye et al. 2004). A brain imaging study using SPECT demonstrated regional cortical reduction in 5-HT_2A binding (Audenaert et al. 2003). Given that dieting and weight loss can have substantial effects on CNS serotonin, it is difficult to ascertain the extent to which these alterations in low-weight patients bear a specific relationship to the eating disorder and to what extent they reflect non-specific effects of nutritional deprivation.

To control for nutritional effects, several groups have studied patients as they reached goal weight during treatment, and in general, results showed a tendency for serotonin function to return towards normal (Brewerton et al. 1996). However, following short-term weight restoration some patients still show altered behavioral responses to a serotonergic drug (Frank et al. 2001).

There has been considerable interest in studies comparing long-term weight recovered patients with healthy controls matched for body mass index (BMI). Results have shown elevated levels of CSF 5-HIAA (Kaye et al. 1991) and diminished sensitivity to the behavioral effects of fenfluramine (Ward et al. 1998), although neuroendocrine responses are not different from healthy controls (O’Dwyer et al. 1996). Moreover, acute tryptophan depletion resulted in a decrease in symptoms of anxiety in long-term recovered individuals (Kaye et al. 2003). Persistent alteration of serotonin function following remission is reflected in the finding that regional 5-HT_2A receptor binding is decreased in individuals who have recovered from the binge-eating/purging subtype of AN (Bailer et al. 2004).

Leptin

In the decade since the discovery of the ob (Lep) gene, there has been increased understanding of the role of leptin in bodyweight regulation. In humans as in laboratory animals, serum and CSF leptin levels show a robust correlation with body fat content and with BMI (Mantzoros et al. 1997; Friedman 2000). Leptin acts in the CNS to decrease meal size and food intake, with interactions in the hypothalamus involving neuropeptide Y, the melanocortins and the neurotransmitter serotonin (Zigman and Elmquist 2003). It is of note that leptin plays a role in brain development in hypothalamic circuits involved in regulation of eating behavior (Elmquist and Flier 2004).

Leptin in bulimia nervosa

As recently reviewed (Monteleone et al. 2004), studies comparing serum leptin levels in patients with BN have generally reported lower levels than in healthy controls matched for BMI. The decrease in leptin levels is most apparent in patients with the most severe symptomatology (Jimerson et al. 2000; Monteleone et al. 2002). These findings are consistent with the hypothesis that low leptin in BN contributes to binge eating and reduced metabolic rate. However, other studies comparing baseline leptin levels in patients with BN and controls have reported variable results, possibly as a result of heterogeneity in patient populations and the inclusion of less symptomatic patients than in the earlier studies (Calandra et al. 2003; Monteleone et al. 2003b; Tagami et al. 2004; Housova et al. 2005). Another possible confounding factor is the finding that leptin levels decrease during short periods of caloric deficit prior to a significant change in body composition (Chin-Chance et al. 2000). Additionally, healthy volunteers following a reduced calorie diet over several weeks show a marked decrease in serum leptin levels (Wolfe et al. 2004). Thus, future studies comparing eating disorder patients with controls will benefit from efforts to monitor the stability of caloric intake over the days preceding study.

An initial report did not demonstrate a significant difference between leptin levels in individuals who had recovered from BN and healthy controls (Gendall et al. 1999). However, a subsequent study which was adjusted for body fat percentage found significantly reduced leptin levels in individuals recovered from the eating disorder (Jimerson et al. 2000).

Leptin in binge-eating disorder

Some studies of patients with binge-eating disorder have shown elevated leptin levels when compared with overweight controls matched for BMI (d’Amore et al. 2001; Adami et al. 2002), while other reports have shown no significant difference (Monteleone et al. 2002; Geliebter et al. 2004). Future studies may help to clarify these variable findings by matching subjects for eating patterns prior to study, as well as for BMI and percentage of body fat.

Leptin in anorexia nervosa

Serum and CSF leptin concentrations in patients with AN are markedly lower than in healthy, normal weight controls, as recently reviewed (Monteleone et al. 2004). Given that circulating leptin levels are substantially influenced by body fat content, low leptin levels in this disorder are most likely a consequence of malnutrition. A substantial portion of serum total leptin is bound to a circulating form of the soluble leptin receptor, with evidence that free (unbound) leptin plays an important role in leptin action (Zastrow et al. 2003). Circulating levels of the binding pr...

Table of contents

• Cover
• Title Page
• Copyright Page
• Contents
• Foreword
• List of editors
• List of Contributor
• 1 Psychobiology of eating disorders
• 2 Genetics of eating disorders
• 3 Sociocultural issues and eating disorders
• 4 Epidemiology of eating disorders
• 5 Body image
• 6 Personality and eating disorders
• 7 Review of brain imaging in anorexia and bulimia nervosa
• 8 Eating disorders in children and adolescents
• 9 Treatment of bulimia nervosa
• 10 Treatment of anorexia nervosa
• Index