BDNF Val66Met polymorphism is linked to elevated levels of serotonin-transporter in the medial prefrontal cortex but not to altered eating behavior.

A single nucleotide polymorphism in the brain derived neurotrophic factor (BDNF)-encoding gene leads to diminished BDNF signaling resulting from Val66Met and has been linked to obesity. Previous imaging studies regarding the impact of BDNF Val66Met on the central serotonin system, which is involved in behavior, cognition and control of satiety, have not focused on body weight or food-intake related behavior. We revisited a cohort of thirty non-depressed individuals with obesity and 15 normal-weight controls. 29 obese and 13 controls underwent [11C]DASB positron emission tomography imaging of the serotonin transporter (5-HTT), Val66Met genotyping and behavioral assessment with the Three-Factor Eating Questionnaire (TFEQ), which measures cognitive restraint, disinhibition and hunger. Volume-of-interest analyses were used to examine the influence of BDNF Val66Met on 5-HTT binding potential (BPND), BMI, and questionnaire scores. Compared to the homozygous Val/Val genotype, Met-carriers showed a significant increase of 5-HTT BPND in the medial prefrontal cortex. The data did not support a BDNF Val66Met effect on TFEQ measures, especially not on cognitive restraint. However, the construct of disinhibition and hunger correlated positively with BMI in homozygous Val-carriers while cognitive restraint did not. This study, despite its small sample size, indicates a possible dampening effect of BDNF Val66Met on prefrontal cortical serotonergic tone.