Depression and the role of genes involved in dopamine metabolism and signalling

Esther M. Opmeer*, Rudie Kortekaas, Andre Aleman

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

72 Citations (Scopus)

Abstract

Major depressive disorder (MDD) is a common psychiatric disorder and leading cause of disability worldwide. It is associated with increased mortality, especially from suicide. Heritability of MDD is estimated around 40%, suggesting that genotyping is a promising field for research into the development of MDD. According to the dopamine theory of affective disorders, a deficiency in dopaminergic neurotransmission may play a role in the major symptoms of MDD. Specific polymorphisms in genes that affect dopamine transmission could increase susceptibility to MDD. To determine the extent to which these genes influence vulnerability to MDD, we discuss genes for crucial steps in dopamine neurotransmission: synthesis, signalling and inactivation. The val158met polymorphism of the COMT gene exemplifies the lack of consensus in the literature: although it is one of the most reported polymorphisms that relates to MDD vulnerability, its role is not corroborated by meta-analysis. Gene-gene interactions and gene-environment interactions provide more explanatory potential than single gene associations. Two notable exceptions are the DRD4 and DAT gene: both have variable tandem repeat polymorphisms which may have a "single gene" influence on susceptibility to MDD. (C) 2010 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)112 - 133
Number of pages22
JournalProgress in Neurobiology
Volume92
Issue number2
DOIs
Publication statusPublished - Oct-2010

Keywords

  • Depression
  • Dopamine
  • Genetics
  • Polymorphisms
  • Tyrosine hydroxylase
  • Dopamine receptors
  • Dopamine transporters
  • DBH
  • COMT
  • MAO
  • CATECHOL-O-METHYLTRANSFERASE
  • BETA-HYDROXYLASE ACTIVITY
  • OXIDASE-A GENE
  • BIPOLAR AFFECTIVE-DISORDER
  • AMINO-ACID DECARBOXYLASE
  • STRESSFUL LIFE EVENTS
  • ANTIDEPRESSANT TREATMENT RESPONSE
  • UNIPOLAR AFFECTIVE-DISORDERS
  • METHYL TRANSFERASE-ACTIVITY
  • SEROTONIN TRANSPORTER GENE

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