Serotonin Receptor 2C -759C/T Polymorphism and Weight Change or Treatment Response to Mirtazapine in Korean Depressive Patients

I have read with great interest the paper by Dr. Lee and colleagues that investigated whether or not the serotonin receptor gene polymorphism (5-HT2C-759C/T) may be associated with a response to mirtazapine or mirtazapine-induced weight gain in patients with major depressive disorder (MDD) in Korean population. 1 They reported that weight change and treatment response after mirtazapine administration was not significantly different among the three 5-HT 2C-759 C/T genotypes. The authors concluded that the 5-HT 2C receptor-759C/ T polymorphism may not be associated with treatment response and weight change after 8 weeks of mirtazapine treatment. To my knowledge, their study is the first one directly investigating the association of 5-HT2C-759C/T with treatment response and weigh change to mirtazapine in Asian patients with MDD, although it failed to demonstrate any valuable ph-armacogenetic findings. Hence various comments and standpoint from other researcher will add up more information for future studies. The acceptable scientific backgrounds for their study may come from several viewpoints: firstly, the 5-HT 2C receptor has different transcriptional activity according to the 5-HT2C-759C/T polymorphism (rs3813929) 2 ; secondly, Abnormalities of the 5-HT2C receptor activity have been suggested to be involved in susceptibility and treatment response in MDD. 3 Despite the clear role of 5-HT2C receptor in antidepressant effects has not been fully explained, the 5-HT2C receptor has been found to be directly implicated in the action mechanism of numerous antidepressants. 3 In addition, paroxetine treatment has been proposed to be implicated in functional de-sensitization of the 5-HT2C receptors. 3 ; thirdly, a number of studies have suggested potential association of-759C/T poly-morphism with the susceptibility to weight gain after various psychotropic agents, 4 although currently available data still indicates that the exact role of it with weight gain should be more explored in a larger studies. 5,6 Finally, mirtazapine is a norad-renergic and specific serotonergic antidepressant (NaSSA). The enhancement of serotonergic neurotransmission of mir-tazpine is specifically mediated by stimulation of 5-HT1 receptors , while mirtazapine antagonizes postsynaptic 5-HT2 receptor. 7 Regarding direct antagonistic activity of mirtazapine on 5-HT2 receptor, it may result in a stimulation of dopami-nergic and adrenergic pathways, implementing antidepres-sant action in behavioral paradigms as well as favoring sleep and sexual function. 8 Despite aforementioned backgrounds, Dr Lee and colleagues failed to find any association of the-759C/T polymor-phism and treatment response/weight change after treatment with mirtazapine, we have to look inside of their study to improve our future researches. …