Baune, Bernhard, Hohoff, Christa, Berger, Klaus, Neumann, Anna, Mortensen, Sunke, Roehrs, Tilmann, Deckert, Jurgen, Arolt, Volker, and Domschke, Katharina (2008) Association of the COMT val158met variant with antidepressant treatment response in major depression. Neuropsychopharmacology, 33 (4). pp. 924-932.

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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.

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