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.
"Down-regulation of D2-type receptors and an attenuated response of striatal dopamine to (palatable) food and food cues are also associated with overweight (Volkow et al., 2002; Stice et al., 2010). Body mass index (BMI) and altered food intake because of attenuated dopamine signalling correlate with polymorphisms of the dopamine receptor genes DRD2, DRD4 and the dopamine-metabolizing enzyme MAO-A (Fuemmeler et al., 2008; Kaplan et al., 2008; Stice et al., 2008; 2010). An epistatic interaction between catecholamine-Omethyltransferase and DAT1 genes on eating psychopathology and BED was reported (Hersrud and Stoltenberg, 2009). "
[Show abstract][Hide abstract] 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):4767-4784. DOI:10.1111/bph.12789 · 4.84 Impact Factor
"Protein that supports the growth, survival, differentiation, and assigned function of neurons; involved in appetite suppression by downstream regulation of melanocortin signaling in the hypothalamus rs6265 Ribases et al., 2003; Ribases et al., 2004; Ribases et al., 2005b; de Krom et al., 2005a; Monteleone et al., 2006b; Dmitrzak-Weglarz et al., 2007; Gratacos et al., 2007; Gelegen et al., 2008; Kaplan et al., 2008; Brandys et al., 2013 Affects the secretion and dendritic trafficking of BDNF protein (Chiaruttini et al., 2009); conflicting findings in EDs rs56164415 Ribases et al., 2003; Ribases et al., 2004; Ribases et al., 2005b; de Krom et al., 2005a; Dmitrzak-Weglarz et al., 2007; Dardennes et al., 2007; Mercader et al., 2008 Affects "
[Show abstract][Hide abstract] ABSTRACT: Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic variants in conferring risk for AN and BN; and (2) explored the involvement of these genes in body mass index (BMI) variations within AN and BN.
Our sample consisted of 745 individuals with AN without a history of BN, 245 individuals with BN without a history of AN, and 321 controls. We genotyped 20 markers with known or putative function among genes selected from leptin, melanocortin, and neurotrophin systems.
There were no significant differences in allele frequencies among individuals with AN, BN, and controls. AGRP rs13338499 polymorphism was associated with lowest illness-related BMI in those with AN (p = 0.0013), and NTRK2 rs1042571 was associated with highest BMI in those with BN (p = 0.0018).
To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. If replicated, our results may serve as an important first step toward gaining a better understanding of weight regulation in eating disorders.
Journal of Psychiatric Research 04/2014; 55(1). DOI:10.1016/j.jpsychires.2014.04.005 · 3.96 Impact Factor
"Therefore, it is plausible that this polymorphism could reflect complex behavioral phenotypes. Indeed, a number of studies have reported associations between the 7R (or aggregated long alleles) and increased risk for various disorders including ADHD (Faraone et al., 2001; Maher et al., 2002), Tourette syndrome (Grice et al., 1996), obsessive compulsive disorder (Camarena et al., 2007; Walitza et al., 2008), pathological gambling (Perez de Castro et al., 1997; Eisenegger et al., 2010), substance abuse (Mcgeary, 2009), bulimia nervosa (Kaplan et al., 2008), conduct disorders (Kirley et al., 2004), autism, and schizophrenia (Emanuele et al., 2010; Lung et al., 2011). Moreover, evidence also supports the associations between these DRD4 risk alleles, especially the 7R, and certain personality traits, including increased novelty seeking (Ebstein et al., 1996), impulsivity (Eisenberg et al., 2007), as well as propensity toward financial risks (Dreber et al., 2009, 2011; Kuhnen and Chiao, 2009). "
[Show abstract][Hide abstract] 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 05/2013; 7:195. DOI:10.3389/fnhum.2013.00195 · 2.99 Impact Factor
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