GTP cyclohydrolase 1 gene haplotypes as predictors of SSRI response in Japanese patients with major depressive disorder

Taro Kishi, Hiroshi Ichinose, Reiji Yoshimura, Yasuhisa Fukuo, Tsuyoshi Kitajima, Toshiya Inada, Hiroshi Kunugi, Tadafumi Kato, Takeo Yoshikawa, Hiroshi Ujike, Giovanna M. Musso, Wakako Umene-Nakano, Jun Nakamura, Norio Ozaki, Nakao Iwata

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Abstract

Background: Tetrahydrobiopterin (BH4) plays an important role in the biosynthesis of serotonin, melatonin and catecholamines, all of which are implicated in the pathophysiology of mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP). Production of BH4 is regulated by GTP cyclohydrolase transcription and activity. Thus, we considered the GTP cyclohydrolase gene (GCH1) to be a good candidate gene in the pathophysiology of MDs and of the serotonin selective reuptake inhibitors (SSRIs) response in MDD, and conducted a case-control study utilizing three SNPs (rs8007267, rs3783641 and rs841) and moderate sample sizes (405 MDD patients, including 262 patients treated by SSRIs, 1022 BP patients and 1805 controls). Method: A multiple logistic regression analysis was carried out to compare the frequencies of each SNP genotype for the target phenotype across patients and controls in several genetic models, while adjusting for possible confounding factors. A clinical response was defined as a decrease of more than 50% from the baseline score on the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as a SIGH-D score of less than 7 at 8 weeks. Result: No associations between three SNPs in GCH1 and MDD or BP were observed; however, GCH1 was associated with SSRI therapeutic response in MDD in all the marker's haplotype analysis (Global P value=0.0379). Conclusions: Results suggest that GCH1 may predict response to SSRI in MDD in the Japanese population. Nevertheless, a replication study using larger samples may be required for conclusive results, since our sample size was small.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalJournal of Affective Disorders
Volume142
Issue number1-3
DOIs
Publication statusPublished - 15-12-2012

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Psychiatry and Mental health

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    Kishi, T., Ichinose, H., Yoshimura, R., Fukuo, Y., Kitajima, T., Inada, T., Kunugi, H., Kato, T., Yoshikawa, T., Ujike, H., Musso, G. M., Umene-Nakano, W., Nakamura, J., Ozaki, N., & Iwata, N. (2012). GTP cyclohydrolase 1 gene haplotypes as predictors of SSRI response in Japanese patients with major depressive disorder. Journal of Affective Disorders, 142(1-3), 315-322. https://doi.org/10.1016/j.jad.2012.05.004