Recent studies have shown that
selective serotonin reuptake inhibitors (
SSRIs) have circadian properties, suggesting that the antidepressive action of
SSRIs may also be attributable to circadian mechanisms. Another study reported an association between clock gene (CLOCK) and improvements in
insomnia symptoms from
SSRIs treatment. Therefore, we examined the association between CLOCK and the efficacy of
fluvoxamine treatment in 121 patients with Japanese
major depressive disorder (MDD). The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a therapeutic response as a decrease of more than a 50% in baseline SIGH-D within 8 weeks, and clinical remission as a SIGH-D score of less than seven at 8 weeks. We selected three tagging SNPs in CLOCK for the subsequent statistical association analysis. We detected a significant association between rs3736544, a synonymous polymorphism in exon 20, and the
fluvoxamine therapeutic response in MDD in the allele/genotype-wise analyses. In addition, remission with
fluvoxamine was also significantly associated with rs3736544. These associations remained significant after Bonferroni correction. Moreover, haplotype analysis findings supported these significant associations, which appeared to be due mainly to rs3736544, in the
fluvoxamine therapeutic remission. Our results indicate that CLOCK genotype may be a predictor of
fluvoxamine treatment response in Japanese MDD. However, our sample size was small, and a replication study using larger samples may be required for conclusive results.