Open AccessEpistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met Polymorphism Impacts Novelty Seeking and Harm Avoidance
Author(s) -
Christian Montag,
Sebastian Markett,
Ulrike Basten,
Christine Stelzel,
Christian J. Fiebach,
Turhan Canli,
Martin Reuter
Publication year - 2010
Publication title -
neuropsychopharmacology
Language(s) - English
Resource type - Journals
eISSN - 1740-634X
pISSN - 0893-133X
DOI - 10.1038/npp.2010.55
Subject(s) - novelty seeking , harm avoidance , novelty , psychology , harm , oncology , medicine , pharmacology , clinical psychology , social psychology , personality , big five personality traits , temperament
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.