ABSTRACT
Tryptophan hydroxylase-2 (TPH2) contributes to alterations in the function of neuronal serotonin (5-HT), which are associated with various psychopathologies, including major depressive disorder (MDD) or suicidal behavior. The methylation of a single CpG site in the promoter region of TPH2 affects gene expression. Suicide and MDD are strongly associated and genetic factors are at least partially responsible for the variability in suicide risk. The aim of the present study was to investigate whether variations in TPH2 methylation in peripheral blood samples may predispose patients with MDD to suicide attempts. TPH2 mRNA expression levels differed significantly between 50 patients with MDD who had attempted suicide (MDD + suicide group) and 75 control patients with MDD (MDD group); TPH2 expression levels were significantly decreased (P=0.0005) in the patients who had attempted suicide. Furthermore, the frequency of TPH2 methylation was 36.0% in the MDD + suicide group, while it was 13.0% in the MDD group. The results of the present study demonstrated that methylation in the promoter region of TPH2 significantly affected the mRNA expression levels of TPH2, thus suggesting that methylation of the TPH2 promoter may silence TPH2 mRNA expression in MDD patients with or without suicidal behavior. In addition, there was a significant correlation between the methylation status of the TPH2 promoter and depression, hopelessness and cognitive impairment in the MDD + suicide group. In conclusion, the present study demonstrated that TPH2 expression was regulated by DNA methylation of the TPH2 promoter region in patients with MDD.
Subject(s)
Depressive Disorder, Major/metabolism , Epigenesis, Genetic , RNA, Messenger/metabolism , Suicide, Attempted/psychology , Tryptophan Hydroxylase/metabolism , Adolescent , Adult , Aged , CpG Islands , DNA Methylation , Depressive Disorder, Major/genetics , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/psychology , Female , Humans , Male , Middle Aged , Promoter Regions, Genetic , Psychiatric Status Rating Scales , RNA, Messenger/genetics , Signal Transduction , Tryptophan Hydroxylase/geneticsABSTRACT
OBJECTIVE: This paper is aimed to explore the adverse reaction condition of Shuanghuangli an injection with three common used signal detecting methods based on SRS database of Jiangsu province, and to evaluate the performance of three methods. METHOD: Three methods would be used to detect the signals based on the SRS database of Jiangsu province. Consistency of the results of these three methods with that proved in descriptions was evaluated by Kappa test. The trend graph of the confidence intervals of several time points was used to demonstrate the trend of the signal. RESULT: The PRR method was consistent with ROR method in high degree in any situation. The results of BCPNN method was close to PRR and ROR method only when the related report count was larger. PRR and ROR methods had higher false positive rate than BCPNN method. CONCLUSION: PRR or ROR method is proposed for signal detecting when the report count is large. BCPNN method is proposed for trend demonstration of signal with graph.
