Item

Abstract

Objective

The brain neurotransmitters serotonin (5-HT) and noradrenaline (NA) are both implicated in the regulation of appetite and energy balance. Disturbances of these systems, i.e. in key areas of feeding control such as the hypothalamus, lead to eating disorders and obesity. The mechanism by which an impaired 5-HT/NA signalling contributes is still unclear.
Methods

A PET study using either central 5-HT transporter (5-HTT)- or NA transporter (NAT)-selective [11C]DASB/[11C]MRB in 65 lean-to-highly obese individuals (BMI range: 19.1–54.1 kg/m2). 5-HTT/NAT binding potential BPND was obtained as PET outcome measures and correlated with BMI.
Results

5-HTT BPND and NAT BPND tend towards an inverse relationship with increasing BMI (e.g., in the midbrain: Fig. 1A; p = 0.13 and p = 0.06, respectively). Such an opponent association is supported by correlative data with neurobehavioral scores (Y-FAS, FEV II), pharmacological stress test results, and follow-up BPND after 6-months diet. Although the participants were free of major depressive disorder (as assessed by structured clinical interview), correlative analyses showed a relationship between midbrain NAT BPND and Beck Depression Inventory (BDI) as an index for sub-threshold depression (r = −0.408; p = 0.07) as well as a correlation between BMI and BDI in both groups (5-HTT: p < 0.01; NAT: p = 0.19; Fig. 1B).
Conclusion

High 5-HTT and low NAT are associated with high BMI. This indicates a potential mechanism in the pathogenesis of human obesity reflecting high NA tone and low 5-HT levels. Together with certain eating behaviours and other biomarkers (pharmacogenotypes) the hypothesized association may lead to more individualised approaches if confirmed. It also questioned the presumed mechanism of action of the drug sibutramine, which is a combined NAT and 5-HTT inhibitor. Sub-threshold depression is an important modulator but may not explain the findings alone.