Association between MC4R rs17782313 polymorphism and overeating behaviors.

BACKGROUND/OBJECTIVES: Melanocortins have a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behavior and depressed mood. SUBJECTS/METHODS: We genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviors was obtained during the in-person assessment. RESULTS: BMI was associated with rs17782313 C allele; however, this finding did not survive correction for multiple testing (P = 0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviors, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n = 152). CONCLUSIONS: To our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behavior, as well as to demonstrate possible mechanisms behind MC4R's influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating.

Alcohol abuse and dysfunctional eating in adolescent girls: the influence of individual differences in sensitivity to reward and punishment.

OBJECTIVE: An unusually high comorbidity of eating disorders and alcohol abuse has been found in clinical and community samples of young women. This paper proposes that individual differences in sensitivity to reward and punishment may influence the propensity of young women to engage in dysfunctional eating and drinking behaviour. METHOD: The Drive for Thinness scale, the Alcohol Use Disorders Identification Test and the BIS/BAS scales were administered to 232 high school girls. RESULTS: Heightened sensitivity to reward was the better predictor of alcohol misuse while heightened sensitivity to both reward and punishment was predictive of dysfunctional eating. When categorised by group, alcohol abusing, dysfunctional eating, and comorbid girls reported greater sensitivity to reward than non-disordered girls. Girls with dysfunctional eating with and without comorbid alcohol abuse reported greater sensitivity to punishment than alcohol abusing only girls. DISCUSSION: These findings suggest that girls who abuse alcohol and have dysfunctional eating may share a vulnerability to heightened sensitivity to reward, yet be differentiated by sensitivity to punishment.

Mucosal mast cell responses and release of mast cell protease-I in infections of mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A.

The dynamics of intestinal mucosal mast cells and the major mucosal mast cell protease were followed during the course of laboratory infections of mice with Hymenolepis diminuta and H. microstoma. The effects of the drug cyclosporin A (CsA), which is both immunosuppressive and selectively anthelmintic depending upon dose regime, were determined. In H. diminuta infections worm expulsion occurred around day 9 and coincided with peak mastocytosis and peak mMCP-I concentrations in tissues and serum. Immunosuppressive treatment with CsA prevented worm expulsion, permitting some individuals to reach maturity, and abrogated mast cell proliferation and mMCP-I production and release. By contrast, H. microstoma infections persisted for 64 days in spite of a considerable mastocyosis in both intestine and bile duct tissues accompanied by a high level of mMCP-I in tissues and serum. A subimmunosuppressive regime of CsA had only limited effects on worms and mast cell numbers and activity. Together these data shed light on the variable mast cell response to gastrointestinal infections and on the potential significance of parasite location in evasion of mast cell action. Use of CsA reveals the contributions of both T cell-dependent mechanisms, including mast cell proliferation and activation, and T cell-independent events in regulating intestinal helminth infections.