Altered dopamine activity after recovery from restricting-type anorexia nervosa.

When ill, women with eating disorders have disturbances of mood and behavior and alterations of catecholamine activity. It is not known whether these alterations are cause or consequence of pathological eating behaviors. To avoid confounding effects of pathologic eating behavior, we studied women who were recovered (> 1 year, normal weight, regular menstrual cycles, no restricting eating pattern, no bingeing or purging) from anorexia nervosa (AN) and bulimia nervosa (BN) compared to healthy control women. Recovered AN women had significantly lower height-adjusted weight than did recovered BN women. CSF HVA (pmol/ml +/- SD), a major metabolite of dopamine, was significantly lower (p < .02) in six restricting-type AN women (131 +/- 49) compared to 19 BN women (216 +/- 73) and at a trend (p < .08) less than 13 bulimic-type AN women (209 +/- 53, p < .06) and 18 control women (202 +/- 57, p < .08). These four groups had similar values for CSF MHPG, a norepinephrine metabolite. Dopamine neuronal function has been associated with motor activity, reward, and novelty seeking. These behaviors are altered in restricting-type AN compared to other eating disorder subtypes. A trait-related disturbance of dopamine metabolism may contribute to a vulnerability to develop this sub-type of eating disorder.     

Altered 5-HT(2A) receptor binding after recovery from bulimia-type anorexia nervosa: relationships to harm avoidance and drive for thinness.

Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN) and bulimia nervosa (BN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5-HT(2A)) receptor, which could contribute to disturbances of appetite and behavior in AN and BN. To avoid the confounding effects of malnutrition, we studied 10 women recovered from bulimia-type AN (REC AN-BN, > 1 year normal weight, regular menstrual cycles, no binging, or purging) compared with 16 healthy control women (CW) using PET imaging and a specific 5-HT(2A) receptor antagonist, [18F]altanserin. REC AN-BN women had significantly reduced [18F]altanserin binding potential relative to CW in the left subgenual cingulate, the left parietal cortex, and the right occipital cortex. [18F]altanserin binding potential was positively related to harm avoidance and negatively related to novelty seeking in cingulate and temporal regions only in REC AN-BN subjects. In addition, REC AN-BN had negative relationships between [18F]altanserin binding potential and drive for thinness in several cortical regions. In conclusion, this study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from bulimia-type AN, particularly in subgenual cingulate regions. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of eating disorders. It is possible that subgenual cingulate findings are not specific for AN-BN, but may be related to the high incidence of lifetime major depressive disorder diagnosis in these subjects.     

Methamphetamine dependent individuals show attenuated brain response to pleasant interoceptive stimuli

Background

Mechano-receptive C-fiber (MR-CF) stimulation via slow stroking of C-fiber rich skin areas can be used to probe the relationship between reward and interoception. Individuals with substance use disorders show impaired reward processing, and dysfunctional interoceptive processing of MR-CF may contribute to this dysfunction. This study predicted that methamphetamine dependent (MD) individuals would exhibit altered responses to MR-CF stimulation in brain regions important for interoception.

Methods

Recently abstinent MD (n = 25) and comparison (CTL, n = 17) subjects received a pleasant interoceptive stimulus (“Soft Touch” consisting of a slow brush stroke) to the palm or forearm during functional magnetic resonance imaging. Subjects were provided with cues signaling stimulation to examine anticipatory and stimulus-related processing. Subjective responses were measured using visual analog scales (VAS).

Results

Groups were similar on behavioral performance and ratings of the interoceptive stimuli, yet MD exhibited lower anterior insula, dorsal striatum, and thalamus activation than CTL, across anticipation and soft touch conditions. The lower the anterior insula activation, the faster the reaction time across conditions in MD, whereas the opposite pattern was evident in CTL. Striatal activation in MD was greater than CTL during anticipation, but lower during soft touch. Greater striatal attenuation was associated with higher VAS pleasantness ratings of soft touch.

Conclusions

MD expend fewer brain processing resources during soft touch, a form of positively-valenced interoceptive stimuli, in brain areas that are important for both interoception and reward. Future studies will ascertain if sustained abstinence from methamphetamine use can normalize aberrant neural interoceptive processing.     

Selective serotonin re-uptake inhibitors in anorexia nervosa

Anorexia nervosa (AN), one of the major eating disorders, is a primarily psychiatric illness affecting a number of adolescents and young adults. AN usually runs a chronic course and is associated with significant morbidity and mortality. Drug therapy has modest success in its treatment. Various pharmacotherapeutic agents are being tested, with variable success. Selective serotonin re-uptake inhibitors are the one class of drug that has been found to be effective in AN, especially in preventing relapse. This article provides an overview of the current literature on the role of selective serotonin re-uptake inhibitors in the treatment of AN.     

Enhanced platelet serotonin 5-HT2A receptor binding in anorexia nervosa and bulimia nervosa.

Some evidence exists to suggest that serotonin 5-HT_2A receptor function is altered in anorexia nervosa and bulimia nervosa. In order to further investigate the 5-HT_2A receptor in eating disorders, platelet [³H]lysergic acid diethylamide ([³H]LSD) binding was studied in ten patients with anorexia nervosa, 23 patients with bulimia nervosa and 33 healthy controls. At admission, B_max for platelet [³H]LSD binding was significantly higher both in the anorexia nervosa group (30.6±4.2 fmol/mg protein; mean±S.D.) and in the bulimia nervosa group (30.8±7.6 fmol/mg protein) than in the control group (23.5 ±6.3 fmol/mg protein; p=0.01 and p=0.003, respectively). K_d was borderline significantly higher among anorexics (median 1.45 nM) and significantly higher among bulimics (median 1.66 nM) than among controls (median 0.95 nM; p=0.05 and 0.003, respectively). The Global Assessment of Functioning score and the body mass index were both significantly negatively correlated to K_d (r=−0.40; p=0.03 and r=−0.41 p=0.03, respectively), but not to B_max. The present study indicates that patients with anorexia nervosa as well as patients with bulimia nervosa have an enhanced 5-HT_2A receptor binding and provides further evidence for a serotonergic dysfunction in eating disorders.     

Efficacy of citalopram in anorexia nervosa: a pilot study.

INTRODUCTION: Anorexia nervosa (AN) still lacks a defined treatment. Since fluoxetine proved effective in weight-restored anorexics, this pilot study evaluates the efficacy of another SSRI, citalopram, in restricting-type AN. EXPERIMENTAL PROCEDURES: Fifty-two female anorectic outpatients were randomized in the citalopram (n=26) and waiting list (n=26) as a control group. Efficacy was assessed using Eating Disorder Inventory-2, Eating Disorder Inventory-Symptom Checklist, State-Trait Anger Expression Inventory, Beck Depression Inventory, Symptom Checklist-90 and Structured Clinical Interview for DSM-IV Axis II Disorders. RESULTS: Thirteen patients dropped-out, thus 19 patients received citalopram and 20 remained in the control group. After 3 months of treatment, the citalopram group showed a decrease on BDI and SCL-90 Depression subscale and an improvement of baseline obsessive compulsive features on SCL-90, EDI-2 impulsiveness and Trait-anger on STAXI. Weight gain was similar in the two groups. DISCUSSION: These preliminary results support the efficacy of citalopram in anorectics. Citalopram seems to improve depression, obsessive-compulsive symptoms, impulsiveness and Trait-anger.     

Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa.

The endocannabinoid system, consisting of two cannabinoid receptors (CB1 and CB2) and the endogenous ligands anandamide (arachidonoylethanolamide (AEA)) and 2-arachidonoylglycerol (2-AG), has been shown to control food intake in both animals and humans, modulating either rewarding or quantitative aspects of the eating behavior. Moreover, hypothalamic endocannabinoids seem to be part of neural circuitry involved in the modulating effects of leptin on energy homeostasis. Therefore, alterations of the endocannabinoid system could be involved in the pathophysiology of eating disorders, where a deranged leptin signalling has been also reported. In order to verify this hypothesis, we measured plasma levels of AEA, 2-AG, and leptin in 15 women with anorexia nervosa (AN), 12 women with bulimia nervosa (BN), 11 women with binge-eating disorder (BED), and 15 healthy women. Plasma levels of AEA resulted significantly enhanced in both anorexic and BED women, but not in bulimic patients. No significant change occurred in the plasma levels of 2-AG in all the patients' groups. Moreover, circulating AEA levels were significantly and inversely correlated with plasma leptin concentrations in both healthy controls and anorexic women. These findings show for the first time a derangement in the production of the endogenous cannabinoid AEA in drug-free symptomatic women with AN or with BED. Although the pathophysiological significance of this alteration awaits further studies to be clarified, it suggests a possible involvement of AEA in the mediation of the rewarding aspects of the aberrant eating behaviors occurring in AN and BED.     

青少年神经性厌食患者治疗前后血清IGF-Ⅰ和瘦素浓度的变化

目的 研究青少年神经性厌食患者治疗前后瘦素和类胰岛素生长因子1(IGF-Ⅰ)浓度的变化.方法 检测11例青少年神经性厌食患者治疗前后的血清瘦素和IGF-Ⅰ浓度,测量身高和体质量,计算体重指数,比较治疗前后血清瘦素和IGF-Ⅰ浓度的变化,并与11例同年龄的健康儿童进行比较.结果 (1)青少年神经性厌食患者血清瘦素和IGF-Ⅰ浓度治疗有效后3个月较治疗前显著增高(P<0.01),但都明显低于正常对照组(P<0.01);(2)无论是正常者还是治疗前和治疗后瘦素和IGF-Ⅰ浓度均与体重指数(BMI)呈显著正相关(P<0.01);(3)无论是正常者还是治疗前和治疗后瘦素与IGF-Ⅰ均呈显著正相关(P<0.01).结论 青少年神经性厌食患者体内瘦素和IGF-Ⅰ浓度在治疗有效前后发生了明显的变化,这种变化与神经性厌食患者脂肪含量的变化相一致.     

Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa

Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of restricted eating coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here. This article is part of a Special Issue entitled 'Central Control of Food Intake'.     

Beryllium-specific immune response in primary cells from healthy individuals

The effect of beryllium (Be) exposure has been extensively studied in patients with chronic beryllium disease (CBD). CBD patients carry mutated MHC class II alleles and show a hyperproliferation of T cells upon Be exposure. The exact mechanism of Be-induced T-cell proliferation in these patients is not clearly understood. It is also not known how the inflammatory and suppressive cytokines maintain a balance in healthy individuals and how this balance is lost in CBD patients. To address these issues, we have initiated cellular and biochemical studies to identify Be-responsive cytokines and other cellular markers that help maintain a balance in healthy individuals. We have established an immune cell model derived from a mixture of peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs). In this article, we demonstrate that pro-inflammatory cytokine IL6 shows decreased release whereas suppressive cytokine IL10 shows enhanced release after 5-10 h of Be treatment. Furthermore, the Be-specific pattern of IL6 and IL10 release is dependent upon induction of threonine phosphorylation of a 45 kDa cytosolic protein (p45), as early as 90 min after Be treatment. Pharmacological inhibition of phosphatidylinositol 3' kinase (PI3'K) by wortmannin and p38 mitogen-activated protein kinase (MAPK) by SB203580 reveal that PI3'K mediates Be-specific p45 phosphorylation and IL6 release, whereas p38 MAPK regulates the release of IL6 and IL10 and the phosphorylation of p45 independent of metal-salt treatment. While the IL10 and IL6 release pathways are uncoupled in these cells, they are linked to phosphorylation of p45. These findings suggest that the balance between IL10 and IL6 release and the correlated p45 phosphorylation are important components of the Be-mediated immune response in healthy individuals.