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

Publication ,  Journal Article
Lohoff, FW; Hodge, R; Narasimhan, S; Nall, A; Ferraro, TN; Mickey, BJ; Heitzeg, MM; Langenecker, SA; Zubieta, J-K; Bogdan, R; Nikolova, YS ...
Published in: Molecular psychiatry
January 2014

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.

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Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

January 2014

Volume

19

Issue

1

Start / End Page

129 / 139

Related Subject Headings

  • Young Adult
  • Vesicular Monoamine Transport Proteins
  • Transfection
  • Psychiatry
  • Polymorphism, Genetic
  • Male
  • Image Processing, Computer-Assisted
  • Humans
  • Genotype
  • Genetic Association Studies
 

Citation

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Chicago
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Lohoff, F. W., Hodge, R., Narasimhan, S., Nall, A., Ferraro, T. N., Mickey, B. J., … Doyle, G. A. (2014). Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing. Molecular Psychiatry, 19(1), 129–139. https://doi.org/10.1038/mp.2012.193
Lohoff, F. W., R. Hodge, S. Narasimhan, A. Nall, T. N. Ferraro, B. J. Mickey, M. M. Heitzeg, et al. “Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.Molecular Psychiatry 19, no. 1 (January 2014): 129–39. https://doi.org/10.1038/mp.2012.193.
Lohoff FW, Hodge R, Narasimhan S, Nall A, Ferraro TN, Mickey BJ, et al. Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing. Molecular psychiatry. 2014 Jan;19(1):129–39.
Lohoff, F. W., et al. “Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.Molecular Psychiatry, vol. 19, no. 1, Jan. 2014, pp. 129–39. Epmc, doi:10.1038/mp.2012.193.
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. Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing. Molecular psychiatry. 2014 Jan;19(1):129–139.

Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

January 2014

Volume

19

Issue

1

Start / End Page

129 / 139

Related Subject Headings

  • Young Adult
  • Vesicular Monoamine Transport Proteins
  • Transfection
  • Psychiatry
  • Polymorphism, Genetic
  • Male
  • Image Processing, Computer-Assisted
  • Humans
  • Genotype
  • Genetic Association Studies