Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.

Published

Journal Article

Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.

Full Text

Duke Authors

Cited Authors

  • Lohoff, FW; Hodge, R; Narasimhan, S; Nall, A; Ferraro, TN; Mickey, BJ; Heitzeg, MM; Langenecker, SA; Zubieta, J-K; Bogdan, R; Nikolova, YS; Drabant, E; Hariri, AR; Bevilacqua, L; Goldman, D; Doyle, GA

Published Date

  • January 2014

Published In

Volume / Issue

  • 19 / 1

Start / End Page

  • 129 - 139

PubMed ID

  • 23337945

Pubmed Central ID

  • 23337945

Electronic International Standard Serial Number (EISSN)

  • 1476-5578

International Standard Serial Number (ISSN)

  • 1359-4184

Digital Object Identifier (DOI)

  • 10.1038/mp.2012.193

Language

  • eng