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Association of the COMT val158met variant with antidepressant treatment response in major depression.

Abstract
In several previous biochemical, pharmacological, and genetic studies, the catechol-O-methyltransferase (COMT) has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of affective disorders. In the present study, 256 patients with major depression (DSM-IV) of Caucasian descent were genotyped for the functional COMT val158met polymorphism and characterized for clinical response to antidepressive pharmacological treatment as measured by intra-individual changes of Hamilton Depression (HAM-D-21) scores over 6 weeks. The COMT 158val/val genotype conferred a significant risk of worse response after 4-6 weeks of antidepressant treatment in patients with major depression (week 4: p=0.003; week 5: p<0.0001; week 6: p<0.0001) after Bonferroni correction for multiple comparisons. The present results strongly point toward a negative influence of the higher activity COMT 158val/val genotype on antidepressant treatment response during the first 6 weeks of pharmacological treatment in major depression, possibly conferred by consecutively decreased dopamine availability. This finding suggests a potentially beneficial effect of an antidepressive add-on therapy with substances increasing dopamine availability individually tailored according to COMT val158met genotype.
AuthorsBernhard T Baune, Christa Hohoff, Klaus Berger, Anna Neumann, Sünke Mortensen, Tilmann Roehrs, Jürgen Deckert, Volker Arolt, Katharina Domschke
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 33 Issue 4 Pg. 924-32 (Mar 2008) ISSN: 0893-133X [Print] England
PMID17522626 (Publication Type: Journal Article)
Chemical References
  • Antidepressive Agents
  • Methionine
  • Catechol O-Methyltransferase
  • Valine
Topics
  • Adult
  • Antidepressive Agents (therapeutic use)
  • Bipolar Disorder (drug therapy, genetics)
  • Catechol O-Methyltransferase (genetics)
  • Depressive Disorder, Major (drug therapy, genetics)
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Methionine (genetics)
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic (genetics)
  • Valine (genetics)

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