Orphan nuclear receptor Rev-erb alpha gene (NR1D1) and fluvoxamine response in major depressive disorder in the Japanese population.
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-erbalpha 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-erbalpha 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.


CONCLUSIONS
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.
Kishi
Taro
T
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan. tarok@fujita-hu.ac.jp
Kitajima
Tsuyoshi
T
Ikeda
Masashi
M
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Kawashima
Kunihiro
K
Okochi
Tomo
T
Ozaki
Norio
N
Iwata
Nakao
N
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use*; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012074:Remission Induction; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D016666:Fluvoxamine