In this study, it was hypothesized that higher COMT activity as conferred by the COMT 158val allele leading to decreased norepinephrine and dopamine availability has a negative effect on antide-pressant drug response in depression.
A sample of 322 unrelated Caucasian patients with affective disorders (DSM-IV: major depression, n = 256, bipolar disorder, n = 66) was characterized and genotyped for the COMT val158met variant. Weekly Hamilton Depression Rating Scale (HAM-D) scores during antidepressant treatment (SSRIs, NSRIs, NaSSA) were assessed. Statistical analysis was performed using stratified and adjusted multivariate ANOVA (Bonferroni post hoc test).
The COMT 158val/val genotype as compared with the 158val/met genotype conferred a significant risk of worse response after 4–6 weeks of antidepressant treatment in patients with affective disorders (week 4: P = 0.030; week 5: P = 0.002; week 6: P = 0.003). Even more significant results were obtained for the subsample restricted to major depression (week 4: P = 0.014; week 5: P = 0.000; week 6: P = 0.000). Statistical comparison of COMT 158val/val vs. COMT 158met/met genotype with respect to therapy response showed a less pronounced negative effect of the COMT 158val/val genotype (week 5: P = 0.037; week 6: P = 0.096) in the sample of patients with major depression. In the subsample of patients with bipolar disorder, major depressive episode, no influence of the COMT val158met variant on HAM-D overall change scores could be detected. Further stratified results are presented.
In patients homozygous for the higher activity COMT 158val allele, the consecutive decreased availability of the monoamines norepinephrine and dopamine might impair the efficacy of antide-pressants during pharmacological treatment in major depression.