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.

Figure 1

Forest plot of studies examining the association between neuroticism and the BDNF Val66Met polymorphism. Met/Met and Val/Met were contrasted with the Val/Val genotypes. SMD, standardized mean differences.

Figure 2

Interaction of BDNF Val66Met and 5-HTTLPR on NEO-PI-R neuroticism scores in the SardiNIA sample (N=2333). Among the carriers of the 5-HTTLPR LL genotype, individuals with one or two copies of the BDNF Met variant tend to score higher on neuroticism (p=0.005). Among individuals with the 5-HTTLPR S variant, there are no significant differences in neuroticism scores between BDNF genotypes (p=0.98).