CLOCK may predict the response to fluvoxamine treatment in Japanese major depressive disorder patients.
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.
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan. tarok@fujita-hu.ac.jp
Taro
T
Kishi
Tsuyoshi
T
Kitajima
Masashi
M
Ikeda
Yoshio
Y
Yamanouchi
Yoko
Y
Kinoshita
Kunihiro
K
Kawashima
Tomo
T
Okochi
Takenori
T
Okumura
Tomoko
T
Tsunoka
Norio
N
Ozaki
Nakao
N
Iwata
D000328:Adult; D044466:Asian People / Q000235:genetics*; D001683:Biological Clocks / Q000502:physiology; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000502:physiology; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D015534:Trans-Activators / Q000235:genetics*; D016896:Treatment Outcome
D056926:CLOCK Proteins; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors; D015534:Trans-Activators; C538943:CLOCK protein, human