Effect of a human serotonin 5-HT2A receptor gene polymorphism on impulsivity: Dependence on cholesterol levels

J Affect Disord. 2016 Dec;206:23-30. doi: 10.1016/j.jad.2016.07.036. Epub 2016 Jul 19.


Background: Impulsivity is multidimensional: Low impulse control may result in behavioural disorders, but acting on the spur of moment may also be advantageous. Previous studies have shown negative associations between different facets of impulsivity and serotonergic function. Other investigations have found negative correlations between serum lipid levels and impulsivity.

Methods: We have investigated whether the functional polymorphism -1438A/G in the serotonin 5-HT2A receptor gene (HTR2A) is associated with impulsivity levels and whether there is any interaction with serum lipid levels. This analysis was based on data of the population-representative Estonian Children Personality Behaviour and Health Study at age 25. Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale.

Results: Subjects with the A/A genotype of the HTR2A -1438A/G polymorphism had higher scores of Maladaptive impulsivity, but not Adaptive impulsivity. In females, high LDL and total cholesterol levels increased the genotype effect. In males, in the highest quartile of total or LDL cholesterol the genotype effect was altered, with G/G homozygotes having the highest Maladaptive impulsivity levels.

Limitations: Only one cohort of the European Youth Heart Study (EYHS) was used in the current study and impulsivity measures were self-reported.

Conclusions: Our results do not support the notion that low cholesterol levels universally lead to higher impulsivity, but it was found that high total and LDL cholesterol levels moderate the effect of the HTR2A gene promoter polymorphism. This suggests that future studies on impulsivity need to consider the interaction of serotonergic measures with the whole range of cholesterol levels.

Keywords: Gender; HTR2A; LDL; Maladaptive Impulsivity.

MeSH terms

  • Adult
  • Cholesterol / blood*
  • Cholesterol, LDL / blood
  • Estonia
  • Female
  • Genotype
  • Health Surveys
  • Humans
  • Impulsive Behavior / physiology*
  • Male
  • Personality Disorders / genetics
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Sex Factors
  • Triglycerides / blood


  • Cholesterol, LDL
  • Receptor, Serotonin, 5-HT2A
  • Triglycerides
  • Cholesterol