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

F. W. Lohoff, R. Hodge, S. Narasimhan, A. Nall, T. N. Ferraro, B. J. Mickey, M. M. Heitzeg, S. A. Langenecker, J. K. Zubieta, R. Bogdan, Y. S. Nikolova, E. Drabant, A. R. Hariri, L. Bevilacqua, D. Goldman, G. A. Doyle

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)129-139
Number of pages11
JournalMolecular Psychiatry
Issue number1
StatePublished - Jan 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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