Brain-Behavior-Immune Interaction: Serum Cytokines and Growth Factors in Patients with Eating Disorders at Extremes of the Body Mass Index (BMI) Spectrum.

Alterations of the immune system are known in eating disorders (EDs), however the importance of cytokine balance in this context has not been clarified. We compared cytokines and growth factors at opposite ends of BMI ranges, in 90 patients classified in relation to BMI, depressive and EDs comorbidities. Serum concentrations of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were determined by a biochip analyzer (Randox Labs). Differences were calculated through ANOVA. Possible predictors of higher cytokine levels were evaluated through regression analysis. IL-1α, IL-10, EGF, and IFN-γ were altered individuals with anorexia nervosa (AN) and binge eating disorder (BED). Night-eating was associated with IL-8 and EGF levels, IL-10 concentrations with post-dinner eating and negatively with sweet-eating, long fasting with higher IFN-γ levels. IL-2 increase was not linked to EDs, but to the interaction of depression and BMI. Altogether, for the first time, IL-1α, IL-10, EGF, and IFN-γ were shown to differ between AN and HCs, and between AN and individuals with obesity with or without BED. Only IL-2 was influenced by depression. Dysfunctional eating behaviors predicted abnormal concentrations of IL-10, EGF, IL-8 and IFN-γ.

Meal-Related Acyl and Des-Acyl Ghrelin and Other Appetite-Related Hormones in People with Obesity and Binge Eating.

OBJECTIVE: Potential mechanisms of abnormal food intake, such as dysregulation of meal-related appetite hormones, including acyl ghrelin (AG) and des-acyl ghrelin (DAG), were investigated among men and women with obesity, with and without binge eating (BE). METHODS: Participants (n = 42: 19 female, 23 male) were assigned to a liquid meal and water condition in counterbalanced order, and blood samples for measuring hormones were obtained before and after these conditions. RESULTS: Participants with BE had significantly lower fasting and postingestive AG concentrations than participants without BE in both conditions. During the meal condition, postprandial decreases in AG concentrations were significantly smaller for the BE group than for the non-BE group. There were no significant differences in DAG by BE group. Leptin increased significantly less after meals for those with BE compared with those without BE. There were no differences in other hormones by BE group. Fasting and postmeal hunger ratings were significantly higher for those with BE than for those without BE. CONCLUSIONS: In individuals with BE, lower fasting AG may be due to downregulation by habitual overeating, and a smaller postmeal decline in AG may contribute to overeating. Lower postmeal leptin concentrations may also contribute to overeating.

Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders.

OBJECTIVE: Caseinolytic protease B (ClpB) produced by Enterobacteria, such as Escherichia coli, has been identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic and anxiogenic neuropeptide. In mice, ClpB induces α-MSH cross-reactive antibodies and activates anorexigenic brain neurons. In patients with eating disorders (ED), anti-ClpB and anti-α-MSH antibodies correlate with psychopathological traits. However, it is not known if ClpB is present in human plasma including ED patients. METHODS: Plasma concentrations of ClpB were measured using a recently developed ClpB immunoassay in female patients with anorexia nervosa, bulimia nervosa, and binge-eating disorder and compared with healthy participants, all characterized by the Eating Disorder Inventory-2 (EDI-2) scale. RESULTS: We found that ClpB was readably detectable in plasma of healthy participants and ED patients and that its concentrations were elevated in ED patients, without significant differences in patient's subgroups. Plasma ClpB concentrations correlated with the EDI-2 scores, with α-MSH as well as with plasma levels of anti-ClpB and anti-α-MSH antibodies. DISCUSSION: These data revealed that bacterial ClpB is naturally present in human plasma and that its concentrations can be elevated in ED patients and associated with ED-related psychopathological traits. These results support a link between bacterial ClpB and the ED pathophysiology. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:805-808).

Psychosocial and metabolic function by smoking status in individuals with binge eating disorder and obesity.

Individuals with binge eating disorder (BED) report smoking to control appetite and weight. Smoking in BED is associated with increased risk for comorbid psychiatric disorders, but its impact on psychosocial functioning and metabolic function has not been evaluated. Participants were 429 treatment-seeking adults (72.4% women; mean age 46.2±11.0years old) with BED comorbid with obesity. Participants were categorized into current smokers (n=66), former smokers (n=145), and never smokers (n=218). Smoking status was unrelated to most historical eating/weight variables and to current eating disorder psychopathology. Smoking status was associated with psychiatric, psychosocial, and metabolic functioning. Compared with never smokers, current smokers were more likely to meet lifetime diagnostic criteria for alcohol (OR=5.51 [95% CI=2.46-12.33]) and substance use disorders (OR=7.05 [95% CI=3.37-14.72]), poorer current physical quality of life, and increased risk for metabolic syndrome (OR=1.80 [95% CI=0.97-3.35]) and related metabolic risks (reduced HDL, elevated total cholesterol). On the other hand, the odds of meeting criteria for lifetime psychiatric comorbidity or metabolic abnormalities were not significantly greater in former smokers, relative to never smokers. Our findings suggest the importance of promoting smoking cessation in treatment-seeking patients with BED and obesity for its potential long-term implications for psychiatric and metabolic functioning.

The effects of repetitive transcranial magnetic stimulation in obese females with binge eating disorder: a protocol for a double-blinded, randomized, sham-controlled trial.

BACKGROUND: Binge eating disorder is a new category in DSM-5 and highly associated with higher body mass index. The neural mechanisms that underlie binge eating are of great interest in order to improve treatment interventions. Brain mechanisms underlying drug and food craving are suggested to be similar: for example, both are reported to be associated with increased neural activity in the orbitofrontal and anterior cingulate cortex, and a diminished regulatory influence from lateral prefrontal circuits. Several studies have begun to assess the potential benefits of brain stimulation in reducing craving and addictive behaviors. Data from a study of a one-off session of transcranial magnetic stimulation in healthy women identified as strong cravers and of individuals with bulimic-type eating disorders, reported a reduction in food craving and binge eating episodes. This provides support for a more extensive investigation of the potential therapeutic benefits of transcranial magnetic stimulation. Lastly, brain imaging studies and a dimensional approach, will improve understanding of the neural correlates of the disorders and of the mode of action of transcranial magnetic stimulation. METHODS/DESIGN: Sixty eligible obese females, with binge eating disorder, will be randomly allocated to receive 20 sessions of transcranial magnetic stimulation intervention (n = 30) or the sham transcranial magnetic stimulation intervention (n = 30) scattered 3 days/week. Thirty eligible controls will complete the baseline assessment. The primary outcome (number of binge eating episodes) will be assed at each treatment sessions, and 8 weeks after intervention completion (follow-up). It is hypothesized that mean weekly binge-eating episodes will be reduced in the intervention group, compared to the sham group, and that the effect will be maintained at follow-up. DISCUSSION: Despite the severity associated with Binge Eating Disorder, there are limited treatment options. This study is an important step in the development of more effective treatments. Importantly, the study is the first to investigating binge eating disorder using a dimensional approach, by looking at the different aspects of the disorder, such as behavioral factors, biological factors, brain circuits and chemistry. TRIAL REGISTRATION: Clinical Trials NCT02180984 . Registered in July 2014.

Weight cycling in bipolar disorder.

BACKGROUND: An association between excess weight and/or weight fluctuations and cardiovascular morbidity and mortality is amply documented. Individuals with bipolar disorder (BD) are differentially affected by overweight/obesity, chaotic eating patterns (e.g., binge eating), as well as cardiovascular morbidity and mortality. Weight cycling (WCYC) is defined as a pattern of repetitive weight loss and gain. METHODS: We sought to determine the relationship between course of illness and BD and WCYC retrospectively as well whether these co-occurring phenotypes identify a biologically distinct subpopulation on the basis of having a unique inflammatory biomarker/biosignature profile. Sociodemographic, clinical, and inflammatory markers were gathered from a well-characterized cohort of actual euthymic adults with BD (n=101) and a healthy control group (n=48). RESULTS: Individuals with BD with a history of WCYC were provided evidence of a greater frequency of prior episodes (i.e., both manic and depressed), as well as of significantly higher levels of circulating IL-6 concentrations when compared to non-WCYC individuals with BD. The association persisted after adjusting for relevant covariates (e.g., BMI, age, number of prior episodes). LIMITATIONS: Include the small control group, differing medication status and that all data relies on personal information. Nevertheless we tried to verify all data as far as clinical disclosure was available. CONCLUSION: The results of this study indicate that adults with BD excessive in weight are not only more susceptible to a relapse-prone course of illness, but also are more likely to present with WCYC. The finding of elevated pro-inflammatory cytokines in this subpopulation may identify a separate subpopulation with greater susceptibility to cardiovascular disease. The overarching aim of personalized treatment and preventive strategies in BD begins with appropriate, empirically supported patient stratification. Our results provide preliminary support for stratifying BD cardiovascular risk on the basis of anthropometrics and WCYC.