Nice guys: Homozygocity for the TPH2 -703G/T (rs4570625) minor allele promotes low aggressiveness and low anxiety

J Affect Disord. 2017 Jun:215:230-236. doi: 10.1016/j.jad.2017.03.045. Epub 2017 Mar 19.


Background: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. We examined whether the TPH2 polymorphism -703G/T (rs4570625) is associated with aggressiveness and impulsivity, and the prevalence of psychiatric disorders, in a population-representative sample.

Methods: We used self and proxy reports on aggressive behaviour in the younger birth cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study collected at age 25, and earlier collected impulsivity and related data of both ECPBHS cohorts.

Results: The TT homozygous males reported less aggressive behaviour in the Life History of Aggression interview at age 25. They also had significantly lower scores in Illinois Bully Scale peer reports, and less ADHD symptoms rated by teachers both at ages 9 and 15. The TT homozygotes of both sexes had the lowest Maladaptive Impulsivity at ages 18 and 25, and the highest Adaptive Impulsivity at age 25. The TT homozygotes also had low depressiveness and trait anxiety by age 25, and the odds ratio for the prevalence of anxiety disorders was 9.38 for the G-allele carriers.

Limitations: The main limitation of the study is the naturally occurring low number of subjects with the TT genotype.

Conclusions: Subjects with the TPH2 rs4570625 TT genotype, especially males, exhibit less aggression and a favourable impulsivity profile, and develop anxiety disorders by young adulthood less often.

Keywords: ADHD symptoms; Aggressiveness; Anxiety disorders; Impulsivity; Tryptophan hydroxylase.

MeSH terms

  • Adolescent
  • Adult
  • Aggression / psychology*
  • Alcoholism / epidemiology
  • Alcoholism / genetics
  • Alcoholism / psychology
  • Alleles
  • Anxiety / epidemiology
  • Anxiety / genetics*
  • Anxiety / psychology*
  • Child
  • Cohort Studies
  • Estonia / epidemiology
  • Homozygote
  • Humans
  • Impulsive Behavior
  • Longitudinal Studies
  • Male
  • Mental Disorders / epidemiology
  • Mental Disorders / genetics
  • Neuropsychological Tests
  • Polymorphism, Genetic / genetics
  • Prevalence
  • Tryptophan Hydroxylase / genetics*
  • Young Adult


  • TPH2 protein, human
  • Tryptophan Hydroxylase