Association of the COMT val158met variant with antidepressant treatment response in major depression.
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.
Baune
Bernhard T
BT
Department of Psychiatry, University of Muenster, Muenster, Germany. bernhard.baune@jcu.edu.au
Hohoff
Christa
C
Berger
Klaus
K
Neumann
Anna
A
Mortensen
Sünke
S
Roehrs
Tilmann
T
Deckert
Jürgen
J
Arolt
Volker
V
Domschke
Katharina
K
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*
D000928:Antidepressive Agents; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine