Argument for a non-linear relationship between severity of human obesity and dopaminergic tone

Alterations in the dopaminergic system have been implicated in both animal and human obesity. However, to date a comprehensive model on the nature and functional relevance of this relationship is missing. In particular, human data remain equivocal inthat seemingly inconsistent reports exist of positive, negative or even no relationships between dopamine D2/D3 receptor availability in the striatum and measures of obesity. Further, data on receptor availability have been commonly interpreted as reflecting receptor density, despite the possibility of an alternative interpretation, namely alterations in basal levels of endogenous dopaminergic tone. Here, we provide a unifying framework that is able to explain the seemingly contradictory findings and offer an alternative and novel perspective on existing data. In particular, we suggest (1) a quadratic relationship between alterations in the dopaminergic system and degree of obesity, and (2) that the observed alterations are driven by shifts in the balance between general dopaminergic tone and phasic dopaminergic signaling. The proposed model consistently integrates human data on molecular and behavioral characteristics of overweight and obesity. Further, the model provides a mechanistic framework accounting not only for the consistent observation of altered (food) reward-responsivity, but also for differences in reinforcement learning, decision-making behavior, and cognitive performance associated with measures of obesity