Association analysis of SIGMAR1 with major depressive disorder and SSRI response

Taro Kishi, Reiji Yoshimura, Tomo Okochi, Yasuhisa Fukuo, Tsuyoshi Kitajima, Takenori Okumura, Tomoko Tsunoka, Kunihiro Kawashima, Yoshio Yamanouchi, Yoko Kinoshita, Wakako Umene-Nakano, Hiroshi Naitoh, Jun Nakamura, Norio Ozaki, Nakao Iwata

Research output: Contribution to journalArticle

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Abstract

Background: Several investigations have suggested the possible involvement of sigma1 non-opioid intracellular receptor 1 (sigma1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline). Method: We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis. Results: In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples. Conclusion: Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results.

Original languageEnglish
Pages (from-to)1168-1173
Number of pages6
JournalNeuropharmacology
Volume58
Issue number7
DOIs
Publication statusPublished - 01-06-2010

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Major Depressive Disorder
Serotonin Uptake Inhibitors
Fluvoxamine
Sertraline
Therapeutics
Population
Case-Control Studies
Logistic Models
Genotype
Regression Analysis
Pharmacology
Interviews
Depression
Phenotype
Mutation

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Kishi, Taro ; Yoshimura, Reiji ; Okochi, Tomo ; Fukuo, Yasuhisa ; Kitajima, Tsuyoshi ; Okumura, Takenori ; Tsunoka, Tomoko ; Kawashima, Kunihiro ; Yamanouchi, Yoshio ; Kinoshita, Yoko ; Umene-Nakano, Wakako ; Naitoh, Hiroshi ; Nakamura, Jun ; Ozaki, Norio ; Iwata, Nakao. / Association analysis of SIGMAR1 with major depressive disorder and SSRI response. In: Neuropharmacology. 2010 ; Vol. 58, No. 7. pp. 1168-1173.
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abstract = "Background: Several investigations have suggested the possible involvement of sigma1 non-opioid intracellular receptor 1 (sigma1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline). Method: We defined a clinical response as a decrease of more than 50{\%} in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis. Results: In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples. Conclusion: Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results.",
author = "Taro Kishi and Reiji Yoshimura and Tomo Okochi and Yasuhisa Fukuo and Tsuyoshi Kitajima and Takenori Okumura and Tomoko Tsunoka and Kunihiro Kawashima and Yoshio Yamanouchi and Yoko Kinoshita and Wakako Umene-Nakano and Hiroshi Naitoh and Jun Nakamura and Norio Ozaki and Nakao Iwata",
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Kishi, T, Yoshimura, R, Okochi, T, Fukuo, Y, Kitajima, T, Okumura, T, Tsunoka, T, Kawashima, K, Yamanouchi, Y, Kinoshita, Y, Umene-Nakano, W, Naitoh, H, Nakamura, J, Ozaki, N & Iwata, N 2010, 'Association analysis of SIGMAR1 with major depressive disorder and SSRI response', Neuropharmacology, vol. 58, no. 7, pp. 1168-1173. https://doi.org/10.1016/j.neuropharm.2010.02.013

Association analysis of SIGMAR1 with major depressive disorder and SSRI response. / Kishi, Taro; Yoshimura, Reiji; Okochi, Tomo; Fukuo, Yasuhisa; Kitajima, Tsuyoshi; Okumura, Takenori; Tsunoka, Tomoko; Kawashima, Kunihiro; Yamanouchi, Yoshio; Kinoshita, Yoko; Umene-Nakano, Wakako; Naitoh, Hiroshi; Nakamura, Jun; Ozaki, Norio; Iwata, Nakao.

In: Neuropharmacology, Vol. 58, No. 7, 01.06.2010, p. 1168-1173.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association analysis of SIGMAR1 with major depressive disorder and SSRI response

AU - Kishi, Taro

AU - Yoshimura, Reiji

AU - Okochi, Tomo

AU - Fukuo, Yasuhisa

AU - Kitajima, Tsuyoshi

AU - Okumura, Takenori

AU - Tsunoka, Tomoko

AU - Kawashima, Kunihiro

AU - Yamanouchi, Yoshio

AU - Kinoshita, Yoko

AU - Umene-Nakano, Wakako

AU - Naitoh, Hiroshi

AU - Nakamura, Jun

AU - Ozaki, Norio

AU - Iwata, Nakao

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Background: Several investigations have suggested the possible involvement of sigma1 non-opioid intracellular receptor 1 (sigma1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline). Method: We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis. Results: In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples. Conclusion: Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results.

AB - Background: Several investigations have suggested the possible involvement of sigma1 non-opioid intracellular receptor 1 (sigma1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline). Method: We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis. Results: In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples. Conclusion: Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results.

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