title: 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.
authors.affiliation: Department of Psychiatry, University of Muenster, Muenster, Germany. bernhard.baune@jcu.edu.au
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.forename: Christa
authors.initials: C
authors.lastname: Hohoff
authors.forename: Klaus
authors.initials: K
authors.lastname: Berger
authors.forename: Anna
authors.initials: A
authors.lastname: Neumann
authors.forename: Sünke
authors.initials: S
authors.lastname: Mortensen
authors.forename: Tilmann
authors.initials: T
authors.lastname: Roehrs
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D014633:Valine / Q000235:genetics*
chemical_list: D000928:Antidepressive Agents; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine