BDNF Val66Met is associated with introversion and interacts with 5-HTTLPR to influence neuroticism

Antonio Terracciano, Toshiko Tanaka, Angelina R. Sutin, Barbara Deiana, Lenuta Balaci, Serena Sanna, Nazario Olla, Andrea Maschio, Manuela Uda, Luigi Ferrucci, David Schlessinger, Paul T. Costa

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


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 (n1560) and the Baltimore Longitudinal Study of Aging (BLSA; n1131). 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 (n15251), 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 × 5-HTTLPR interaction in a larger SardiNIA sample (n2333). 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.

Original languageEnglish (US)
Pages (from-to)1083-1089
Number of pages7
Issue number5
StatePublished - Apr 2010
Externally publishedYes


  • BDNF Val66Met
  • Depression
  • GWA
  • Gene-gene interaction.
  • Personality
  • Serotonin transporter

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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