title: BDNF Val66Met is associated with introversion and interacts with 5-HTTLPR to influence neuroticism.
abstract: Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurotransmission, and has been linked to neuroticism, a major risk factor for psychiatric disorders. A recent genome-wide association (GWA) scan, however, found the BDNF Val66Met polymorphism (rs6265) associated with extraversion but not with neuroticism. In this study, we examine the links between BDNF and personality traits, assessed using the Revised NEO Personality Inventory (NEO-PI-R), in a sample from SardiNIA (n=1560) and the Baltimore Longitudinal Study of Aging (BLSA; n=1131). Consistent with GWA results, we found that BDNF Met carriers were more introverted. By contrast, in both samples and in a meta-analysis inclusive of published data (n=15251), we found no evidence for a main effect of BDNF Val66Met on neuroticism. Finally, on the basis of recent reports of an epistatic effect between BDNF and the serotonin transporter, we explored a Val66Met x 5-HTTLPR interaction in a larger SardiNIA sample (n=2333). We found that 5-HTTLPR LL carriers scored lower on neuroticism in the presence of the BDNF Val variant, but scored higher on neuroticism in the presence of the BDNF Met variant. Our findings support the association between the BDNF Met variant and introversion and suggest that BDNF interacts with the serotonin transporter gene to influence neuroticism.
authors.affiliation: National Institute on Aging, NIH, DHHS, Baltimore, MD 21224, USA. terraccianoa@mail.nih.gov
authors.forename: Antonio
authors.initials: A
authors.lastname: Terracciano
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Angelina R
authors.initials: AR
authors.lastname: Sutin
authors.forename: Barbara
authors.initials: B
authors.lastname: Deiana
authors.forename: Lenuta
authors.initials: L
authors.lastname: Balaci
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: Nazario
authors.initials: N
authors.lastname: Olla
authors.forename: Andrea
authors.initials: A
authors.lastname: Maschio
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Paul T
authors.initials: PT
authors.lastname: Costa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010551:Personality / Q000235:genetics*; D010556:Personality Tests; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins