2. Academic Validation
  3. Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing

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

  • Mol Psychiatry. 2014 Jan;19(1):129-39. doi: 10.1038/mp.2012.193.
F W Lohoff 1,  R Hodge 1,  S Narasimhan 1,  A Nall 1,  T N Ferraro 1,  B J Mickey 2,  M M Heitzeg 2,  S A Langenecker 2,  J-K Zubieta 2,  R Bogdan 3,  Y S Nikolova 4,  E Drabant 5,  A R Hariri 4,  L Bevilacqua 6,  D Goldman 6,  G A Doyle 1
Affiliations

Affiliations

  • 1 Translational Research Laboratories, Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
  • 2 Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
  • 3 1] Department of Psychology and Neuroscience, Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA [2] Department of Psychology, Washington University in St Louis, St Louis, MO, USA.
  • 4 Department of Psychology and Neuroscience, Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
  • 5 23andMe, Mountain View, CA, USA.
  • 6 Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA.
PMID: 23337945 DOI: 10.1038/mp.2012.193
Abstract

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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