1. ¹Department of Psychiatry, University of Muenster, Muenster, Germany
2. ²Department of Psychiatry, James Cook University, Townsville, QLD, Australia
3. ³Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany
4. ⁴Department of Psychiatry, University of Wuerzburg, Wuerzburg, Germany

Correspondence: Professor BT Baune, Department of Psychiatry, School of Medicine, James Cook University, Townsville, QLD 4811, Australia. Tel: +61 7 4781 6731; Fax: +61 7 4781 6219; E-mail: bernhard.baune@jcu.edu.au

Received 21 December 2006; Revised 26 March 2007; Accepted 25 April 2007; Published online 23 May 2007.

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.