The impact of COMT, BDNF and 5-HTT brain-genes on the development of anorexia nervosa: a systematic review

Eat Weight Disord. 2021 Jun;26(5):1323-1344. doi: 10.1007/s40519-020-00978-5. Epub 2020 Aug 11.

Abstract

Purpose: The genetic aspect of anorexia nervosa (AN) involving specific genes of the central-nervous-system has not yet been clearly understood. The aim of this systematic review is to assess the impact of three candidate genes of the brain: catechol-O-methyltransferase, brain-derived neurotrophic factor (BDNF) and serotonin transporter protein, on the susceptibility to AN and identify whether a clear connection persists between each of the gene-polymorphisms and AN.

Methods: A total of 21 articles were selected for this review conforming to the PRISMA guidelines. Detailed keyword combinations were implemented within specific databases such as MEDLINE, SCIENCEDIRECT and PUBMED.

Results: The catechol-O-methyltransferase gene-polymorphism did not show any change in phenotypic variation between AN and control subjects; but the familial association was rather strong with an over-transmission of the H allele. The latter also correlated with several dimensions of the Temperament and Character Inventory (TCI) scale. A notable relation was indicated between BDNF gene-polymorphism and anorexia-restrictive in terms of phenotypic distribution; the Met66-allele also depicted high association with anorexic behavioral traits. The 5-HTTLPR gene-polymorphism was found to be significantly associated with AN susceptibility with an over-transmission of the S-allele from parents to offspring.

Conclusion: The systematic review distinctively emphasized the genetic contribution of the brain-genes on the development of AN. Despite significant study findings, no clear and standardized genetic route was determined to be the cause of AN development. Future research is needed on these specific genes to closely monitor the genetic polymorphisms and their mechanism on AN susceptibility.

Level of evidence: I, systematic review.

Keywords: Anorexia nervosa; BDNF and 5-HTT; Brain genes; COMT.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Anorexia Nervosa* / genetics
  • Brain
  • Brain-Derived Neurotrophic Factor / genetics
  • Catechol O-Methyltransferase* / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Serotonin Plasma Membrane Transport Proteins / genetics

Substances

  • Brain-Derived Neurotrophic Factor
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • COMT protein, human
  • Catechol O-Methyltransferase