Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men

Abstract

The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF). Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [(11)C]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [(11)C]WAY-100635. Several single nucleotide polymorphisms were associated with [(11)C]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [(11)C]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with (123)I-beta-CIT as ligand. Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.