EXAMINING THE ROLE OF DOPAMINE D2 RECEPTOR AND DOPAMINE TRANSPORTER GENES REGULATION IN BINGE EATING

Binge Eating disorder (BED) is clinically comorbid and shares many characteristics with classical substance use disorders, such as loss of control despite knowledge of adverse consequences. Preclinical and clinical studies, focused on the neurochemical regulation of reward-related signalling pathways evoked by binge eating, suggest alterations in dopaminergic system. In this study, we first investigated the genetic and epigenetic contribution of dopamine transporter (DAT) and dopamine D2 receptor (DRD2) genes in saliva samples of patients suffering from BED and Bulimia Nervosa (BN). We analysed the DNA methylation levels at gene promoters, and we observed a significant hypomethylation of selective CpG sites for both genes (respectively 1 CpG site for DRD2 and 2 CpG sites for DAT) respect to controls. In addition, studying Caenorhabditis elegans feeding behaviours, we have been able to suggest the nematode as a possible model resembling binge eating behaviours when worms are subjected to starvation and stressful procedures. Of relevance, and somehow consistently with our human results, we observed that the altered food intake occurring in wild type nematodes was reverted in worms where it was induced a loss of function of the two genes ortholog of human DAT and DRD2 (dat1 and dop-2, respectively). These findings highlight an important evolutionarily conserved role of dopaminergic system genes in binge eating behaviour and their epigenetic modulation in BED is of relevance in order to suggest possible biomarkers and new targets to treat this disorder.