Document Detail


Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing.
MedLine Citation:
PMID:  23337945     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.Molecular Psychiatry advance online publication, 22 January 2013; doi:10.1038/mp.2012.193.
Authors:
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-22
Journal Detail:
Title:  Molecular psychiatry     Volume:  -     ISSN:  1476-5578     ISO Abbreviation:  Mol. Psychiatry     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607835     Medline TA:  Mol Psychiatry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Translational Research Laboratories, Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
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