Single‐nucleotide polymorphisms and mRNA expression for melatonin synthesis rate‐limiting enzyme in recurrent depressive disorder

Abstract

Depressive disorder (DD) is characterised by disturbances in blood melatonin concentration. It is well known that melatonin is involved in the control of circadian rhythms, sleep included. The use of melatonin and its analogues has been found to be effective in depression therapy. Melatonin synthesis is a multistage process, where the last stage is catalysed by acetylserotonin methyltransferase (ASMT), the reported rate-limiting melatonin synthesis enzyme. Taking into account the significance of genetic factors in depression development, the gene for ASMT may become an interesting focus for studies in patients with recurrent DD. The goal of the study was to evaluate two single-nucleotide polymorphisms (SNPs) (rs4446909; rs5989681) of the ASMT gene, as well as mRNA expression for ASMT in recurrent DD-affected patients. We genotyped two polymorphisms in a group of 181 recurrent DD patients and in 149 control subjects. The study was performed using the polymerase chain reaction/restriction fragment length polymorphism method. The distribution of genotypes in both studied SNPs in the ASMT gene differed significantly between DD and healthy subjects. The presence of AA genotype of rs4446909 polymorphism and of GG genotype of rs5989681 polymorphism was associated with lower risk for having recurrent DD. In turn, patients with depression were characterised by reduced mRNA expression for ASMT. In addition, ASMT transcript level in both recurrent DD patients and in healthy subjects depended significantly on genotype distributions in both polymorphisms. In conclusion, our results suggest the ASMT gene as a susceptibility gene for recurrent DD.

Psychotropic medications affecting biological rhythm

“…In depressed patients, DLMO is usually delayed and melatonin levels are decreased (67,68). In depressive patients there are some single nucleotide polymorphisms (SNPs) in the melatonin pathway such as arylalkylamine N-acetyltransferase (AANAT) (69) and a rate-limiting melatonin enzyme acetylserotonin methyltransferase (ASMT) (70). Melatonin is a prototype of chronobiotics and the chemical code of darkness (43).…”

Retracted: Anti‐inflammatory properties of tianeptine on lipopolysaccharide‐induced changes in microglial cells involve toll‐like receptor‐related pathways

“…Brain inflammatory processes are causally related to the enhanced neurodegeneration changes and reduced neurogenesis observed in the course of depression. Moreover, numerous studies have found that depression is associated with elevated levels of proinflammatory cytokines (Kubera et al 2000;Maes et al 2009;Dowlati et al 2010;Szczesny et al 2014) and with an increased rate of single nucleotide polymorphisms within proinflammatory genes (Galecki et al 2010). Microglia are considered the main source of cytokines in the brain (Hanisch 2002).…”

The Possibility of Applying a Combination of Allelic Variants of IL-1β Gene and WWC1 Gene for Assessing Susceptibility to PTSD (Pilot Investigation)

“…Allelic variants SNP rs17070145 are considered as genetic link between features of the memory mechanisms and anxiety and depressive disorders. Results of researches indicates that variants of more efficiency of hippocampal LTP and higher performance of episodic memory ("CT" and "TT") are associated with increasing the likelihood of PTSD development [33], while "CC" variant rs17070145 is associated with depressive disorder [34]. Role of the immune system in synaptic plasticity is becoming increasingly apparent [35][36][37].…”