Orphan Nuclear Receptor Rev-erb Alpha Gene (NR1D1) and Fluvoxamine Response in Major Depressive Disorder in the Japanese Population

Abstract

Background: Sleep-wake disturbance, frequently observed in major depressive disorder (MDD), negatively influences clinical status. Treatment with antidepressants also reportedly affects circadian rhythms. In a recent in vitro study, the nuclear receptor Rev-erbα was reported to be related to circadian rhythms, and was shown to be involved in the biological action of lithium therapy. Therefore, we examined the association between the orphan nuclear receptor Rev-erbα gene (NR1D1) and the efficacy of fluvoxamine treatment in 118 Japanese patients with major depressive disorder. Methods: The scores of the MDD patients in this study on the 17 items of the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-D) were 12 or higher. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8 weeks and clinical remission as a SIGH-D score of less than 7 at 8 weeks. We selected 3 ‘tagging SNPs’ in NR1D1 for the following association analysis. Results: We did not detect a significant association between NR1D1 and the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis or haplotype-wise analysis. Conclusion: Our results suggest that NR1D1 does not play a major role in the therapeutic response to fluvoxamine in Japanese MDD patients. However, because our sample was small, a replication study using another population and a larger sample will be required for conclusive results.