Altered cortical thickness and attentional deficits in adolescent girls and women with bulimia nervosa.

BACKGROUND: Frontostriatal and frontoparietal abnormalities likely contribute to deficits in control and attentional processes in individuals with bulimia nervosa and to the persistence of dysregulated eating across development. This study assessed these processes and cortical thickness in a large sample of adolescent girls and women with bulimia nervosa compared with healthy controls. METHODS: We collected anatomical MRI data from adolescent girls and women (ages 12-38 yr) with full or subthreshold bulimia nervosa and age-matched healthy controls who also completed the Conners Continuous Performance Test-II (CPT-II). Groups were compared on task performance and cortical thickness. Mediation analyses explored associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms and age. RESULTS: We included 60 girls and women with bulimia nervosa and 54 controls in the analyses. Compared with healthy participants, those with bulimia nervosa showed increased impulsivity and inattention on the CPT-II, along with reduced thickness of the right pars triangularis, right superior parietal and left dorsal posterior cingulate cortices. In the bulimia nervosa group, exploratory analyses revealed that binge eating frequency correlated inversely with cortical thickness of frontoparietal and insular regions and that reduced frontoparietal thickness mediated the association between age and increased symptom severity and inattention. Binge eating frequency also mediated the association between age and lower prefrontal cortical thickness. LIMITATIONS: These findings are applicable to only girls and women with bulimia nervosa, and our cross-sectional design precludes understanding of whether cortical thickness alterations precede or result from bulimia nervosa symptoms. CONCLUSION: Structural abnormalities in the frontoparietal and posterior cingulate regions comprising circuits that support control and attentional processes should be investigated as potential contributors to the maintenance of bulimia nervosa and useful targets for novel interventions.

Recent advances in neuroimaging to model eating disorder neurobiology.

The eating disorders (EDs) anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are severe psychiatric disorders with high mortality. There are many symptoms, such as food restriction, episodic binge eating, purging, or excessive exercise that are either overlapping or lie on opposite ends of a scale or spectrum across those disorders. Identifying how specific ED behaviors are linked to particular neurobiological mechanisms could help better categorize ED subgroups and develop specific treatments. This review provides support from recent brain imaging research that brain structure and function measures can be linked to disorder-specific biological or behavioral variables, which may help distinguish ED subgroups, or find commonalities between them. Brain structure and function may therefore be suitable research targets to further study the relationship between dimensions of behavior and brain function relevant to EDs and beyond the categorical AN, BN, and BED distinctions.

Restrictive eating behaviors are a nonweight-based marker of severity in anorexia nervosa.

OBJECTIVE: The purpose of this study was to compare the type and frequency of restrictive eating behaviors across the two subtypes of anorexia nervosa (AN; restricting [ANr] and binge eating/purging [ANbp]) using ecological momentary assessment (EMA) and to determine whether subtype differences in restrictive eating behaviors were attributable to severity of the disorder or the frequency of binge eating. METHOD: Participants (N = 118) were women at least 18 years of age with full (n = 59) or subthreshold (n = 59) AN who participated in a two week (EMA) protocol. RESULTS: General estimating equations revealed that individuals with ANbp generally reported more frequent restrictive eating behaviors than individuals with ANr. These differences were mostly accounted for by greater severity of eating psychopathology, indicating that the presence and frequency of restrictive eating behaviors in AN may be nonweight-based markers of severity. Binge eating frequency did not account for these findings. DISCUSSION: The present findings are especially interesting in light of the weight-based severity rating in the DSM-5.

Web-based treatment program using intensive therapeutic contact for patients with eating disorders: before-after study.

BACKGROUND: Although eating disorders are common in the Netherlands, only a few patients are treated by mental health care professionals. To reach and treat more patients with eating disorders, Tactus Addiction Treatment developed a web-based treatment program with asynchronous and intensive personalized communication between the patient and the therapist. OBJECTIVE: This pilot study evaluated the web-based treatment program using intensive therapeutic contact in a population of 165 patients with an eating disorder. METHODS: In a pre-post design with 6-week and 6-month follow-ups, eating disorder psychopathology, body dissatisfaction, Body Mass Index, physical and mental health, and quality of life were measured. The participant's satisfaction with the web-based treatment program was also studied. Attrition data were collected, and participants were classified as noncompleters if they did not complete all 10 assignments of the web-based treatment program. Differences in baseline characteristics between completers and noncompleters were studied, as well as reasons for noncompletion. Furthermore, differences in treatment effectiveness, treatment adherence, and baseline characteristics between participants of the three major eating disorder diagnostic groups EDNOS (n=115), BN purging (n=24), and BN nonpurging (n=24) were measured. RESULTS: Of the 165 participants who started the web-based treatment program, 89 participants (54%) completed all of the program assignments (completers) and 76 participants (46%) ended the program prematurely (noncompleters). Severe body dissatisfaction and physical and mental health problems seemed to have a negative impact on the completion of the web-based treatment program. Among the participants who completed the treatment program, significant improvements were found in eating disorder psychopathology (F=54.6, df = 68, P<.001, d=1.14). Body dissatisfaction, quality of life, and physical and mental health also significantly improved, and almost all of these positive effects were sustained up to 6 months after the participants had completed the web-based treatment program. Body Mass Index improved only within the group of participants suffering from obesity. The improvement in eating disorder psychopathology occurred in all three eating disorder diagnostic groups, and the percentage of completers did not differ significantly between these groups. Participants' satisfaction with the treatment program, as well as with their therapist, was high, and participants indicated that they would recommend the program to other patients with eating disorders. CONCLUSIONS: The results of this study suggest that the web-based treatment program has the potential to improve eating disorder psychopathology in patients with different types of eating disorders.

The relationship between eating disorder psychopathology and health-related quality of life within a community sample.

PURPOSE: Recent research has begun investigating the impact of eating disorders on health-related quality of life (QOL). The present study examined the impact of eating disorder psychopathology on QOL within a community sample. METHODS: Two hundred and fourteen women completed questionnaires assessing eating disorder symptoms, body dissatisfaction, body checking and body avoidance behaviors, and general psychopathology. RESULTS: Eating disturbance and body image dissatisfaction were associated with poorer QOL. In addition, eating disorder psychopathology uniquely predicted QOL above and beyond the variance accounted for by general psychopathology. Both subjective bulimic episodes and objective bulimic episodes were associated with impairments in QOL. CONCLUSIONS: These results indicate that eating disorder psychopathology may adversely affect the lives of women within the community. Early intervention and detection could reduce the negative impact of eating disorder psychopathology on women's lives and protect individuals with mild eating disorder symptoms from a further reduction in QOL.

GABAB receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice.

Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient knockout (KO) mice compared to WT mice. Treatment with the GABABR agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABABR signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice.

Regional grey matter volume abnormalities in bulimia nervosa and binge-eating disorder.

This study investigated whether bulimia nervosa (BN) and binge-eating disorder (BED) are associated with structural brain abnormalities. Both disorders share the main symptom binge-eating, but are considered differential diagnoses. We attempted to identify alterations in grey matter volume (GMV) that are present in both psychopathologies as well as disorder-specific GMV characteristics. Such information can help to improve neurobiological models of eating disorders and their classification. A total of 50 participants (patients suffering from BN (purge type), BED, and normal-weight controls) underwent structural MRI scanning. GMV for specific brain regions involved in food/reinforcement processing was analyzed by means of voxel-based morphometry. Both patient groups were characterized by greater volumes of the medial orbitofrontal cortex (OFC) compared to healthy controls. In BN patients, who had increased ventral striatum volumes, body mass index and purging severity were correlated with striatal grey matter volume. Altogether, our data implicate a crucial role of the medial OFC in the studied eating disorders. The structural abnormality might be associated with dysfunctions in food reward processing and/or self-regulation. The bulimia-specific volume enlargement of the ventral striatum is discussed in the framework of negative reinforcement through purging and associated weight regulation.

Changes of body composition in bulimia nervosa: increased visceral fat and adrenal gland size.

OBJECTIVE: To study the hypothesis that young women suffering from active bulimia nervosa (BN) have more visceral fat and increased adrenal gland volumes (AGV) than healthy controls (HC). METHODS: Thirteen patients with BN of purging type and 11 healthy age and weight matched women (HC), aged between 19 and 36 years (mean 24 +/- 3 years), with a BMI of 19 to 29 (mean 24 +/- SD 3) were examined. BN was diagnosed by DSM-IV criteria and the severity of illness by the Eating Disorder Inventory (EDI-2). Whole body fat distribution and AGV were determined using a whole body magnetic resonance (MR) scan (T1w) and a 3D-sequence (T1w) at 1.5 Tesla. Salivary cortisol was determined at 9 AM and 4 PM. RESULTS: BN patients had significantly more visceral adipose tissue (VAT) (HC, 1589.3 +/- 967.6 ml versus 927.2 +/- 428.4 ml, p < .05) and an increased relative AGV (0.068% of body volume versus 0.048% of body volume, p < .05) compared with HC, although waist circumference and BMI did not differ. Although the VAT part in the upper abdomen was increased, especially the VAT of lower abdomen along with the pelvis or any subcutaneous fat compartment was not increased. CONCLUSIONS: The increase of the VAT volume and the increased AGV in BN women with purging point to chronic high stress levels associated with a hyperactivity of the hypothalamic-pituitary-adrenal axis in these patients. This is the first MR study showing morphological changes in stress associated endocrine organs of young BN patients.

Examining the Impact of Estrogen on Binge Feeding, Food-Motivated Behavior, and Body Weight in Female Rats.

OBJECTIVE: Binge-eating disorder is associated with diminished self-control, emotional distress, and obesity. In this context, women are nearly twice as likely to develop binge-eating disorder and depression relative to men. Here, the physiological, psychological, and endocrine parameters were characterized in female rats subjected to a binge-eating protocol. METHODS: Nonrestricted female Long Evans rats (n = 8/group) received 2-hour restricted access to a high-fat diet (HFD) (4.54 kcal/g) every day or every third day. The progression of estrous cycling, the functional relevance of estrogen signaling for binge feeding, and binge-induced changes in food motivation were measured. RESULTS: Female rats developed a binge pattern of feeding that included alternation between caloric overconsumption and compensatory voluntary restriction without impacting estrous cycling. Notably, rats that received daily HFD exposure progressively decreased binge meals. Estrogen replacement in normal cycling or ovariectomized rats mimicked the reduction in body weight in female rats that received daily HFD access. Operant responding was unaffected by binge feeding; however, estrogen augmented operant performance in HFD-exposed rats. CONCLUSIONS: Collectively, these data suggest that estrogen protects against binge-induced increases in body weight gain without affecting food motivation in female rats.

Neurobiology of anorexia and bulimia nervosa.

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by which they can modulate brain 5-HT functional activity and anxious mood. People with AN enter a vicious cycle which accounts for the chronicity of this disorder because caloric restriction results in a brief respite from dysphoric mood. However, malnutrition and weight loss, in turn, produce alterations in many neuropeptides and monoamine function, perhaps in the service of conserving energy, but which also exaggerates dysphoric mood. In summary, this article reviews findings in brain chemistry and neuroimaging that shed new light on understanding the psychopathology of these difficult and frustrating disorders.

Binge-like sucrose consumption reduces the dendritic length and complexity of principal neurons in the adolescent rat basolateral amygdala.

A compelling body of evidence suggests that the worldwide obesity epidemic is underpinned by excessive sugar consumption, typified by the modern western diet. Furthermore, evidence is beginning to emerge of maladaptive changes in the mesolimbic reward pathway of the brain in relation to excess sugar consumption that highlights the importance of examining this neural circuitry in an attempt to understand and subsequently mitigate the associated morbidities with obesity. While the basolateral amygdala (BLA) has been shown to mediate the reinforcing properties of drugs of abuse, it has also been shown to play an important role in affective and motivated behaviours and has been shown to undergo maladaptive changes in response to drugs of abuse and stress. Given the overlap in neural circuitry affected by drugs of abuse and sucrose, we sought to examine the effect of short- and long-term binge-like sucrose consumption on the morphology of the BLA principal neurons using an intermittent-access two-bottle choice paradigm. We used Golgi-Cox staining to impregnate principal neurons from the BLA of short- (4 week) and long-term (12 week) sucrose consuming adolescent rats and compared these to age-matched water controls. Our results indicate possibly maladaptive changes to the dendritic architecture of BLA principal neurons, particularly on apical dendrites following long-term sucrose consumption. Specifically, our results show reduced total dendritic arbor length of BLA principal neurons following short- and long-term sucrose consumption. Additionally, we found that long-term binge-like sucrose consumption caused a significant reduction in the length and complexity of apical dendrites. Taken together, our results highlight the differences between short- and long-term binge-like sucrose consumption on BLA principal neuron morphology and are suggestive of a perturbation in the diverse synaptic inputs to these neurons.

Hypothalamic expression of inflammatory mediators in an animal model of binge eating.

Binge eating episodes are characterized by uncontrollable, distressing eating of a large amount of highly palatable food and represent a central feature of bingeing related eating disorders. Research suggests that inflammation plays a role in the onset and maintenance of eating-related maladaptive behavior. Markers of inflammation can be selectively altered in discrete brain regions where they can directly or indirectly regulate food intake. In the present study, we measured expression levels of different components of cytokine systems (IL-1, IL-6, IL-18, TNF-α and IFN-É£) and related molecules (iNOS and COX2) in the preoptic and anterior-tuberal parts of the hypothalamus of a validated animal model of binge eating. In this animal model, based on the exposure to both food restriction and frustration stress, binge-like eating behavior for highly palatable food is not shown when animals are exposed to the frustration stress during the estrus phase. We found a characteristic down-regulation of the IL-18/IL-18 receptor system (with increased expression of the inhibitor of the pro-inflammatory cytokine IL-18, IL-18BP, together with a decreased expression of the binding chain of the IL-18 receptor) and a three-fold increase in the expression of iNOS specifically in the anterior-tuberal region of the hypothalamus of animals that develop a binge-like eating behavior. Differently, when food restricted animals were stressed during the estrus phase, IL-18 expression increased, while iNOS expression was not significantly affected. Considering the role of this region of the hypothalamus in controlling feeding related behavior, this can be relevant in eating disorders and obesity. Our data suggest that by targeting centrally selected inflammatory markers, we may prevent that disordered eating turns into a full blown eating disorder.

Binge-like intake of HFD attenuates alcohol intake in rats.

Binge eating and binge alcohol intake are behavioral manifestations of pathological feeding and alcohol use disorder (AUD), respectively. Binge-feeding and AUD have high comorbidity with other psychiatric disorders such as depression, which could have important implications for the management of these conditions. Importantly, these behaviors share many common features suggesting a singular etiology. However, the nature by which binge-feeding affects the development or maintenance of AUD is unclear. The present study examined the impact of a binge-feeding from a nutritionally complete high-fat diet (HFD) on initiation and maintenance of alcohol intake, anxiolytic behavior and central genetic changes in brain regions that control alcohol-reinforced behaviors. To do this, male Long-Evans rats received chow (controls) or HFD every three days (HFD-3D) or every day (HFD-ED) for 5weeks. Rodent chow and water were available ad-libitum to all groups throughout the experiment. Following 5weeks of HFD cycling, 20.0% ethanol or 2.0% sucrose intake was evaluated. In addition, anxiety-like behavior was measured using a light-dark box apparatus. Both HFD-3D and -ED groups of rats consumed significantly large amount of food during 2h HFD access sessions and reduced their chow intake in the next 22h. Surprisingly, binge-fed rats displayed attenuated acquisition of alcohol intake whereas sucrose consumption was unaffected. Rats exposed to HFD spent more time in the light side compared to chow controls, indicating that binge-feeding induced anxiolytic effects. In addition, alterations in the brain neurotensin system were observed following HFD exposure. These data indicate that binge-feeding behavior induces behavioral and genetic changes that help explain how alcohol intake is influenced by co-morbid eating disorders.

VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation.

Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons. While KO mice showed no differences on chow, they presented a reduced high-fat diet (HFD) intake and resisted to HFD-induced obesity. Specific activation of midbrain LepR neurons promoted VMAT2-dependent feeding on chow and HFD. When tested with an intermittent access to HFD where first 2.5-h HFD eating (binge-like) and 24-h HFD feeding were measured, KO mice exhibited more binge-like, but less 24-h HFD feeding. Interestingly, leptin inhibited 24-h HFD feeding in controls but not in KO mice. Thus, VMAT2-mediated neurotransmission from midbrain LepR neurons contributes to both binge-like eating and HFD feeding regulation.

Increased naive CD4+ and B lymphocyte subsets are associated with body mass loss and drive relative lymphocytosis in anorexia nervosa patients.

Anorexia nervosa (AN) is an atypical form of malnutrition with peculiar changes in the immune system. We hypothesized that different lymphocyte subsets are differentially affected by malnutrition in AN, and thus, our aim was to investigate the influence of body mass loss on the variability of lymphocyte subsets in AN patients. A group of 66 adolescent female patients, aged 12-17 years, referred for their first episode of either AN or feeding or eating disorders not elsewhere classified were studied upon admission (46 AN-restricting subtype, 11 AN-binge/purging subtype, and 9 feeding or eating disorders not elsewhere classified). Ninety healthy adolescents served as controls. White blood cells and lymphocyte subsets were analyzed by flow cytometry. Relationships with the body mass index (BMI) z score were assessed in linear models adjusted by diagnostic subtype and age. Leukocyte numbers were lower in AN patients than in controls, and relative lymphocytosis was observed in AN-restricting subtype. Lower CD8+, NK, and memory CD8+ counts were found in eating disorder patients compared with controls. No differences were found for CD4+ counts or naive and memory CD4+ subsets between the groups. Negative associations between lymphocyte percentage and the BMI z score, as well as between the B cell counts, naive CD4+ percentage and counts, and the BMI z score, were found. In conclusion, increased naive CD4+ and B lymphocyte subsets associated with body mass loss drive the relative lymphocytosis observed in AN patients, which reflects an adaptive mechanism to preserve the adaptive immune response.

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.

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.

Leptin in anorexia nervosa.

Serum leptin levels are low in untreated anorexia nervosa, but studies of the exact relationship between leptin and body weight and the impact of refeeding in anorectics are limited. Therefore, we studied serum leptin, insulin-like growth factor I, and other endocrine parameters in female anorectics before and after gaining weight and in female normal body weight controls. Leptin levels in untreated anorectics were significantly lower than those in normal body weight controls (3.6 +/- 1.6 vs. 12.0 +/- 6.9 ng/mL; P < 0.001), and they uncoupled from body weight in a nonlinear relationship, suggesting a threshold effect at lowest body weights. Leptin increased significantly with refeeding (5.6 +/- 3.8 ng/mL; P < 0.01). The significant linear correlations of leptin with body mass index in the anorectics after weight gain and in normal body weight controls (r = 0.69; P < 0.001 and r = 0.76; P < 0.001, respectively) are consistent with a normal physiological increase in leptin with weight gain. Leptin and insulin-like growth factor I were highly correlated, even after controlling for body weight (r = 0.63; P = 0.001) during starvation, but were no longer significantly correlated after body weight gain in the anorectics or the normal body weight controls. Further studies are necessary to elucidate the relationship of leptin to neuroendrocrine abnormalities seen in starvation and to determine a possible contribution of leptin to difficulties with weight restoration in anorexia nervosa.

Adiponectin in anorexia nervosa and bulimia nervosa.

To study the role of adiponectin, a novel adipocyte-specific secreted protein, on the pathophysiology of eating disorders, circulating levels of fasting adiponectin, leptin, insulin, and glucose were measured in 31 female patients with anorexia nervosa (AN) and in 11 with bulimia nervosa. Hormone levels were compared with 16 age-matched, normal body weight controls, six healthy constitutionally thin subjects, and nine obese subjects. Moreover, changes in levels were reevaluated after nutritional treatment and weight gain in 13 patients with AN. Serum adiponectin concentrations in AN and bulimia nervosa were significantly lower than those in normal-weight controls. These results were unexpected because the levels were high in constitutionally thin subjects and low in obese subjects, which provide a negative correlation with body mass index (BMI) and body fat mass. In contrast, serum leptin levels correlated very well with BMI and fat mass among all the patients and controls. The insulin resistance was significantly low in AN and high in obese subjects. The concentrations of adiponectin after weight recovery increased to the normal level despite a relatively small increase in BMI. These findings suggest that abnormal feeding behavior in the patients with eating disorders may reduce circulating adiponectin level, and weight recovery can restore it.

Osteoporosis in eating disorders: a follow-up study of patients with anorexia and bulimia nervosa.

This study prospectively investigated the course of bone mineral density (BMD) in patients with anorexia nervosa (AN) and bulimia nervosa (BN) over a 3.6-yr follow-up period. From an initial sample of 47 female patients with an eating disorder (T1), 38 (n = 24 AN; n = 14 BN) were reassessed at follow-up (T2) (participation rate, 80.1%). For nonrecovered AN patients at T2, prevalence rates of osteopenia (-1.0 SD > or = T-score > -2.5 SD) and osteoporosis (T-score < or = -2.5 SD) at the lumbar spine were 54.2 and 20.8%, respectively. Due to an annual loss of lumbar spine BMD (-3.7 +/- 4.9%) in the chronic AN patients and a slight but insignificant annual increase (0.7 +/- 1.7%) for those who recovered, the difference in BMD between both outcome groups was more pronounced at follow-up (0.93 +/- 0.13 vs. 1.14 +/- 0.13 g/cm2; P < 0.01). Nonrecovered AN patients with binge eating/purging type showed a significantly reduced BMD compared with patients with the restricting type (0.87 +/- 0.13 vs. 1.02 +/- 0.08 g/cm2; P = 0.02). Both at baseline and follow-up, AN patients had increased rates of bone resorption, as measured by urinary desoxypyridinoline, compared with a control group (n = 42) (11.4 +/- 4.4 vs. 10.4 +/- 7.8, P < 0.001, vs. 5.6 +/- 2.4 and 10.4 +/- 7.8 nM/mM creatinine, P < 0.05, respectively). The subtype of AN and body mass index were best predictors for BMD at the lumbar spine at follow-up (R2 = 0.576). With one exception, all bulimic patients had BMD and markers of bone turnover within the normal range. These results suggest that patients with chronic AN, particularly of the binge eating/purging type, are at high risk for osteoporosis and may need additional therapy to prevent bone loss.