Background:
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.
Methods:
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).
Results:
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.
Conclusions:
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.
