title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences (Ms Vaht and Dr Harro), and Department of Educational Science, Faculty of Social Sciences and Education, University of Tartu, Tartu, Estonia (Dr Kiive); National Institute for Health Development, Estonian Centre of Behavioural and Health Sciences, Tallinn, Estonia (Dr Veidebaum).
authors: Mariliis
authors: M
authors: Vaht
authors: Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences (Ms Vaht and Dr Harro), and Department of Educational Science, Faculty of Social Sciences and Education, University of Tartu, Tartu, Estonia (Dr Kiive); National Institute for Health Development, Estonian Centre of Behavioural and Health Sciences, Tallinn, Estonia (Dr Veidebaum).
authors: Evelyn
authors: E
authors: Kiive
authors: Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences (Ms Vaht and Dr Harro), and Department of Educational Science, Faculty of Social Sciences and Education, University of Tartu, Tartu, Estonia (Dr Kiive); National Institute for Health Development, Estonian Centre of Behavioural and Health Sciences, Tallinn, Estonia (Dr Veidebaum).
authors: Toomas
authors: T
authors: Veidebaum
authors: Division of Neuropsychopharmacology, Department of Psychology, Estonian Centre of Behavioural and Health Sciences (Ms Vaht and Dr Harro), and Department of Educational Science, Faculty of Social Sciences and Education, University of Tartu, Tartu, Estonia (Dr Kiive); National Institute for Health Development, Estonian Centre of Behavioural and Health Sciences, Tallinn, Estonia (Dr Veidebaum). jaanus.harro@ut.ee.
authors: Jaanus
authors: J
authors: Harro
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D001008:Anxiety Disorders / Q000235:genetics*; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019964:Mood Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C493449:SLC18A1 protein, human; D050493:Vesicular Monoamine Transport Proteins
keywords: VMAT1; affective disorders; alcohol use; anxiety; cohort effect