Association of a functional variant of the nitric oxide synthase 1 gene with personality, anxiety, and depressiveness

Dev Psychopathol. 2012 Nov;24(4):1225-35. doi: 10.1017/S0954579412000661.


A functional promoter polymorphism of the nitric oxide synthase 1 gene first exon 1f variable number tandem repeat (NOS1 ex1f-VNTR) is associated with impulsivity and related psychopathology. Facets of impulsivity are strongly associated with personality traits; maladaptive impulsivity with neuroticism; and adaptive impulsivity with extraversion. Both high neuroticism and low extraversion predict anxiety and depressive symptoms. The aim of the present study was to evaluate the effect of the NOS1 ex1f-VNTR genotype and possible interaction with environmental factors on personality, anxiety, and depressiveness in a population-representative sample. Short allele carriers had higher neuroticism and anxiety than individuals with the long/long (l/l) genotype. Male short/short homozygotes also had higher extraversion. In the face of environmental adversity, females with a short allele had higher scores of neuroticism, anxiety, and depressiveness compared to the l/l genotype. Males were more sensitive to environmental conditions when they had the l/l genotype and low extraversion. In conclusion, the NOS1 ex1f-VNTR influences personality and emotional regulation dependent on gender and environment. Together with previous findings on the effect of the NOS1 genotype on impulse control, these data suggest that NOS1 should be considered another plasticity gene, because its variants are associated with different coping strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Analysis of Variance
  • Anxiety / genetics*
  • Anxiety Disorders / genetics
  • Depression / genetics*
  • Extraversion, Psychological
  • Female
  • Gene-Environment Interaction
  • Genotype
  • Humans
  • Impulsive Behavior / genetics
  • Introversion, Psychological
  • Male
  • Minisatellite Repeats / genetics
  • Neuroticism
  • Nitric Oxide Synthase Type I / genetics*
  • Personality / genetics*
  • Promoter Regions, Genetic
  • Sex Factors


  • NOS1 protein, human
  • Nitric Oxide Synthase Type I