Sex differences in serotonin-hypothalamic connections underpin a diminished sense of emotional well-being with increasing body weight.

BACKGROUND/OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress related to weight remain largely unknown. PARTICIPANTS/METHODS: Here we combined positron emission tomography, using the serotonin transporter (5-HTT) radiotracer [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, with functional connectivity magnetic resonance imaging, the Beck Depression Inventory (BDI-II) and the Impact of Weight on Quality of Life-Lite questionnaire (IWQOL-Lite) to investigate the role of central serotonin in the severity of depression (BDI-II), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a group of lean to morbidly obese individuals (n=28), we found sex differences in the 5-HTT availability-related connectivity of the hypothalamus. Males (n=11) presented a strengthened connectivity to the lateral orbitofrontal cortex, whereas in females (n=17) we found strengethened projections to the ventral striatum. Both regions are known as reward regions involved in mediating the emotional response to food. Their resting-state activity correlated positively to the body mass index (BMI) and IWQOL-Lite scores, suggesting that each region in both sexes also underpins a diminished sense of emotional well-being with body weight. Contrarily to males, we found that in females also the BDI-II positively correlated with the BMI and by trend with the activity in ventral striatum, suggesting that in females an increased body weight may convey to other mood dimensions than those weight-related ones included in the IWQOL-Lite. CONCLUSIONS: This study suggests sex differences in serotonin-hypothalamic connections to brain regions of the reward circuitry underpinning a diminished sense of emotional well-being with an increasing body weight.

The central nervous norepinephrine network links a diminished sense of emotional well-being to an increased body weight.

OBJECTIVES: The neurobiological mechanisms linking obesity to emotional distress remain largely undiscovered. METHODS: In this pilot study, we combined positron emission tomography, using the norepinephrine transporter (NET) tracer [(11)C]-O-methylreboxetine, with functional connectivity magnetic resonance imaging, the Beck depression inventory (BDI), and the impact of weight on quality of life-Lite questionnaire (IWQOL-Lite), to investigate the role of norepinephrine in the severity of depression (BDI), as well as in the loss of emotional well-being with body weight (IWQOL-Lite). RESULTS: In a small group of lean-to-morbidly obese individuals (n=20), we show that an increased body mass index (BMI) is related to a lowered NET availability within the hypothalamus, known as the brain's homeostatic control site. The hypothalamus displayed a strengthened connectivity in relation to the individual hypothalamic NET availability to the anterior insula/frontal operculum, as well as the medial orbitofrontal cortex, assumed to host the primary and secondary gustatory cortex, respectively (n=19). The resting-state activity in these two regions was correlated positively to the BMI and IWQOL-Lite scores, but not to the BDI, suggesting that the higher the resting-state activity in these regions, and hence the higher the BMI, the stronger the negative impact of the body weight on the individual's emotional well-being was. CONCLUSIONS: This pilot study suggests that the loss in emotional well-being with weight is embedded within the central norepinephrine network.

Neural correlates of the volitional regulation of the desire for food.

OBJECTIVE: In this study, we investigate the brain mechanisms of the conscious regulation of the desire for food using functional magnetic resonance imaging. Further, we examine associations between hemodynamic responses and participants' cognitive restraint of eating (CRE), as well as their susceptibility to uncontrolled eating. SUBJECTS: Seventeen non-vegetarian, right-handed, female Caucasian participants (age: 20-30 years, mean 25.3 years±3.1 s.d.; BMI: 20.2-31.2 kg m(-2), mean 25.1±3.5 s.d.). MEASUREMENTS: During scanning, our participants viewed pictures of food items they had pre-rated according to tastiness and healthiness. Participants were either allowed to admit to the desire for the food (ADMIT) or they were instructed to downregulate their desire using a cognitive reappraisal strategy, that is, thinking of negative long-term health-related and social consequences (REGULATE). RESULTS: Comparing the hemodynamic responses of the REGULATE with the ADMIT condition, we observed robust activation in the dorsolateral prefrontal cortex (DLPFC), the pre-supplementary motor area, the inferior frontal gyrus (IFG), the dorsal striatum (DS), the bilateral orbitofrontal cortex (OFC), the anterior insula and the temporo-parietal junction (TPJ). Activation in the DLPFC and the DS strongly correlated with the degree of dietary restraint under both conditions. CONCLUSION: Cortical activation in the DLPFC, the pre-supplementary motor area and the inferior frontal gyrus (IFG) are known to underpin top-down control, inhibition of learned associations and pre-potent responses. The observed hemodynamic responses in the lateral OFC, the DS, the anterior insula and the TPJ support the notion of reward valuation and integration, interoceptive awareness, and self-reflection as key processes during active regulation of desire for food. In conclusion, an active reappraisal of unhealthy food recruits the brain's valuation system in combination with prefrontal cognitive control areas associated with response inhibition. The correlations between brain responses and CRE suggest that individuals with increased cognitive restraint show an automatic predisposition to regulate the hedonic aspects of food stimuli. This cognitive control might be necessary to counterbalance a lack of homeostatic mechanisms.