Association analysis of SIGMAR1 with major depressive disorder and SSRI response.
BACKGROUND
Several investigations have suggested the possible involvement of sigma 1 non-opioid intracellular receptor 1 (sigma 1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma 1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma 1 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).


METHODS
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.


CONCLUSIONS
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.
Kishi
Taro
T
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. tarok@fujita-hu.ac.jp
Yoshimura
Reiji
R
Okochi
Tomo
T
Fukuo
Yasuhisa
Y
Kitajima
Tsuyoshi
T
Okumura
Takenori
T
Tsunoka
Tomoko
T
Kawashima
Kunihiro
K
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Umene-Nakano
Wakako
W
Naitoh
Hiroshi
H
Nakamura
Jun
J
Ozaki
Norio
N
Iwata
Nakao
N
D000328:Adult; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D016666:Fluvoxamine / Q000627:therapeutic use; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D017480:Receptors, sigma / Q000235:genetics*; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000097605:Sigma-1 Receptor
D016666:Fluvoxamine; D017480:Receptors, sigma; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D000097605:Sigma-1 Receptor