A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa
ABSTRACT The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene-gene interactions in mediating maximum lifetime BMIs in BN.
We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the dopamine-4 receptor gene (DRD4) and either the Val66Met or the -270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype.
In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene-gene interaction groups.
These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects.
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ABSTRACT: Eating disorders, like anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorders (BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, serotonin (5-HT) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced dopaminergic, 5-HTergic and noradrenergic neurotransmission and compensatory changes, at least in dopamine 2-type and 5-HT2C/2A receptors, have been related to pathophysiology of AN in humans and animal models. Also, in disorders and animal models of BN and BED monoaminergic neurotransmission is downregulated, but receptor level changes are different from those seen in AN. A hypofunctional dopamine system or overactive α2-adrenoceptors may contribute to an attenuated response to (palatable) food and result in hedonic binge eating. Evidence for the efficacy of monoaminergic treatments for AN is limited, while more support exists for the treatment of BN or BED with monoaminergic drugs.British Journal of Pharmacology 05/2014; 171(20). DOI:10.1111/bph.12789 · 4.99 Impact Factor
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ABSTRACT: Human beings are an extraordinarily altruistic species often willing to help strangers at a considerable cost (sometimes life itself) to themselves. But as Darwin noted "… he who was ready to sacrifice his life, as many a savage has been, rather than betray his comrades, would often leave no offspring to inherit his noble nature." Hence, this is the paradox of altruism. Twin studies have shown that altruism and other prosocial behavior show considerable heritability and more recently a number of candidate genes have been identified with this phenotype. Among these first provisional findings are genes encoding elements of dopaminergic transmission. In this article we will review the evidence for the involvement of one of these, the dopamine D4 receptor (DRD4) gene, in shaping human prosocial behavior and consider the methodologies employed in measuring this trait, specific molecular genetic findings and finally, evidence from several Gene × Environment (G × E) studies that imply differential susceptibility of this gene to environmental influences.Frontiers in Human Neuroscience 01/2013; 7:195. DOI:10.3389/fnhum.2013.00195 · 2.90 Impact Factor
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ABSTRACT: Data suggest that low levels of dopamine D2 receptors and attenuated responsivity of dopamine-target regions to food intake is associated with increased eating and elevated weight. There is also growing (although mixed) evidence that genotypes that appear to lead to reduced dopamine signaling (e.g., DRD2, DRD4, and DAT) and certain appetite-related hormones and peptides (e.g., ghrelin, orexin A, leptin) moderate the relation between dopamine signaling, overeating, and obesity. This chapter reviews findings from studies that have investigated the relation between dopamine functioning and food intake and how certain genotypes and appetite-related hormones and peptides affect this relation.01/2011; 6:81-93. DOI:10.1007/7854_2010_89