Single nucleotide polymorphisms, variable number tandem repeats and allele influence on serotonergic enzyme modulators for aggressive and suicidal behaviors: A review

Pharmacol Biochem Behav. 2019 May;180:74-82. doi: 10.1016/j.pbb.2019.03.008. Epub 2019 Mar 27.

Abstract

The serotonergic system plays key regulatory roles in cognition and emotion. Several lines of evidence suggest that genetic variation is associated with aggressive and suicidal behaviors. Genetic studies have largely focused on three types of variations: single nucleotide polymorphisms (SNPs), variable number tandem repeats (VNTRs), and alleles. 95 published papers (49 papers for aggression and 46 for suicide) were reviewed to summarize the impact of SNPs, VNTRs, and alleles of tryptophan hydroxylase (TPH, the rate-limiting enzyme in serotonin [5-HT] synthesis), 5-HT transporter (5-HTT), serotonergic receptors, monoamine oxidase (an enzyme that catalyzes 5-HT degradation) on aggression and suicidal behaviors. These study samples include healthy controls, psychiatric disease patients, and animal models. This article mainly reviews studies on the relationship between 5-HT transmissions and genetic variations involved in aggression (particularly impulsive aggression) or suicide in people with different ethnicities and psychiatric disorders. We found that most SNPs, VNTRs, and alleles exerted influences on aggression or suicide. Only A128C in TPH1, A138G in 5-HT2A, and L type in the VNTR of monoamine oxidase A (MAOA) affected both aggression and suicide. The associations between some genetic variations and aggression/suicide may be influenced by gender, age, ethnicity, psychiatric disease, and even parenting or prenatal stress. These findings may help clarify how genetic and environmental factors influence the development of aggressive and suicidal behaviors.

Keywords: Aggression; MAOA; Serotoninergic system; Suicide; Violence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aggression / physiology*
  • Alleles*
  • Animals
  • Child
  • Female
  • Humans
  • Male
  • Mice
  • Minisatellite Repeats / physiology*
  • Monoamine Oxidase / genetics
  • Polymorphism, Single Nucleotide / physiology*
  • Receptors, Serotonin / genetics
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Suicide*
  • Tryptophan Hydroxylase / genetics
  • Young Adult

Substances

  • Receptors, Serotonin
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Tryptophan Hydroxylase
  • Monoamine Oxidase
  • monoamine oxidase A, human