The Impact of a Single Nucleotide Polymorphism in SIGMAR1 on Depressive Symptoms in Major Depressive Disorder and Bipolar Disorder
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Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers.
A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively.
In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode.
The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.
KeywordsAntidepressants Bipolar disorder Major depressive disorder Mood stabilizers Psychiatry Sigma-1 receptor SIGMAR1
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number : HC15C1405).
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.
Laura Mandelli, Sheng-Min Wang, Changsu Han, Soo-Jung Lee, Ashwin A. Patkar, Prakash S. Masand, Chi-Un Pae, and Alessandro Serretti declare no personal, financial, commercial, or academic conflicts of interest.
Compliance with Ethics Guidelines
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. All the patients were informed in detail about the aims and the procedures of the study and they signed an informed consent prior to inclusion into the study. The protocol and the informed consent were approved by the local ethical committee (approval number HC10TISI0031).
The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request. All authors presented no conflicts of interest to disclose.
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