4.7 Article

Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met Polymorphism Impacts Novelty Seeking and Harm Avoidance

Journal

NEUROPSYCHOPHARMACOLOGY
Volume 35, Issue 9, Pages 1860-1867

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2010.55

Keywords

BDNF Val66Met; DRD2/ANKK1 Taq Ia; personality; novelty seeking; harm avoidance

Funding

  1. German Research Foundation [DFG FI 848/3-1]

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Mounting evidence from animal studies show that the mesolimbic dopaminergic pathways are modulated by the brain-derived neurotrophic factor (BDNF). This study investigates in N = 768 healthy Caucasian participants the influence of two prominent functional single-nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ankyrin repeat and kinase domain containing 1 (ANKK1) gene (DRD2 Taq Ia/ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through dopaminergic mesolimbic circuitry. Carriers of the 66Met + /A1 + variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D-2 receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to show a modulatory role for BDNF genetic variation on genetically mediated differences in the mesolimbic dopaminergic system in the context of human personality. Neuropsychopharmacology (2010) 35, 1860-1867; doi: 10.1038/npp.2010.55; published online 21 April 2010

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