title: A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity.
abstract: BACKGROUND
  Neuronal nitric oxide synthase (NOS1) knockout results in increased impulsive aggression in mice under adverse housing conditions. In line with this, we have previously shown that a functional promoter polymorphism of NOS1, termed NOS1 ex1f-VNTR, is associated with impulsivity-related traits and related disorders.
  
  
  OBJECTIVE
  This study aims to examine whether adverse environment interacts with the risk allele on impulsivity-related measures.
  
  
  METHODS
  We here studied a population-based cohort of Estonian pupils, recruited at the age of 9 years and followed up for another 9 years. For 435 subjects, measures on impulsivity (Adaptive and Maladaptive Impulsivity Scale, BIS-11, Stop Signal data, and Visual Comparison Test, VCT), environmental conditions (stressful life events and family environment), and NOS1 ex1f-VNTR genotype were available.
  
  
  RESULTS
  We found a genotype main effect in that presence of a short NOS1 ex1f-VNTR allele was associated with higher levels of adaptive impulsivity, especially in males, but also worse performance in the VCT and the Stop Signal test. Both stressful life events as well as adverse family environment interacted with the risk genotype to increase maladaptive impulsivity.
  
  
  CONCLUSIONS
  This study provides further evidence that short alleles of NOS1 ex1f-VNTR go along with impulsive behavior. In the absence of adverse environmental conditions, this may lead to a beneficial effect as functional forms of impulsivity are affected. This however is reversed under negative conditions, as dysfunctional impulsivity is increased under these circumstances. This data provides evidence that NOS1 ex1f-VNTR is subject to balancing selection potentially explaining persistence of the risk allele in the population.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080, Würzburg, Germany. reif_a@klinik.uni-wuerzburg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kiive
authors.forename: Triin
authors.initials: T
authors.lastname: Kurrikoff
authors.forename: Marika
authors.initials: M
authors.lastname: Paaver
authors.forename: Sabine
authors.initials: S
authors.lastname: Herterich
authors.forename: Kenn
authors.initials: K
authors.lastname: Konstabel
authors.forename: Tiia
authors.initials: T
authors.lastname: Tulviste
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Jaanus
authors.initials: J
authors.lastname: Harro
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D015331:Cohort Studies; D004957:Estonia; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics*; D008016:Life Change Events; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I