A Functional Vesicular Monoamine Transporter 1 (VMAT1) Gene Variant Is Associated with Affect and the Prevalence of Anxiety, Affective, and Alcohol Use Disorders in a Longitudinal Population-Representative Birth Cohort Study

Int J Neuropsychopharmacol. 2016 Jul 5;19(7):pyw013. doi: 10.1093/ijnp/pyw013. Print 2016 Jul.


Background: Inter-individual differences in the monoaminergic systems have been shown to moderate the risk for a lifetime history of anxiety, affective, and alcohol use disorders. A common single nucleotide polymorphism in the vesicular monoamine transporter 1 gene (VMAT1 rs1390938 G/A; Thr136Ile) has been reported as functional in vitro and associated with bipolar disorder and anxiety. We aimed at assessing the association between the VMAT1 genotype, affect, and affect-related psychiatric disorders in a longitudinal population-representative study.

Methods: We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9- (recalled at ages 15 and 18 years, n=579) and 15- (recalled at ages 18 and 25 years; n=654) year-old children provided self-reports on impulsivity, anxiety, depressiveness, neuroticism, and alcohol use. In addition, psychiatric assessment based on DSM-IV was carried out in the older cohort at age 25 years.

Results: Subjects homozygous for the less prevalent A (136Ile) allele reported lower maladaptive impulsivity, state and trait anxiety, depressiveness, and neuroticism and were less likely to have been diagnosed with an affective, anxiety, and/or alcohol use disorder by young adulthood. While in the younger cohort alcohol use started at younger age, this birth cohort effect was dependent on genotype: only G allele carriers and in particular the GG homozygotes started alcohol use earlier.

Conclusions: VMAT1 rs1390938/Thr136Ile is associated with mood, personality, and alcohol use in the general population. Subjects homozygous for the "hyperfunction" allele (AA; Ile/Ile) appear to be more resilient to these disorders.

Keywords: VMAT1; affective disorders; alcohol use; anxiety; cohort effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect
  • Alcoholism / genetics*
  • Alleles
  • Anxiety Disorders / genetics*
  • Databases, Factual
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Mood Disorders / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Prevalence
  • Vesicular Monoamine Transport Proteins / genetics*
  • Young Adult


  • SLC18A1 protein, human
  • Vesicular Monoamine Transport Proteins