mRNA editing was assessed in prefrontal cortex of 24 MDD(Suic), 21 MDD(NoSuic), and 56 NC using next generation sequencing. mRNA expression of 5-HT(2C)R and editing enzymes (ADAR1-2) was assessed by real-time PCR.
Serotonin receptor 2C (HTR2C) has been postulated as being involved in the etiology or pathophysiology of mental disorders such as bipolar disorder, major depression and schizophrenia.
Of the six HTR2C SNPs, only the T allele of the -759C/T SNP showed borderline significant associations with higher body mass index (BMI) (0.23 kg m(-2); (95% confidence interval (CI): 0.01-0.44); P=0.051) and increased risk of lifetime major depressive disorder (MDD) (Odds ratio (OR): 1.13 (95% CI: 1.01-1.22), P=0.02).
Here we overviewed the genetic, expression and RNA editing studies suggesting the close relationship between HTR2C and major mental disorders including schizophrenia, bipolar disorder and major depression.
The new antidepressant agomelatine is the first melatonergic antidepressant with an innovative mode of action: it is a melatonergic MT(1), MT(2) receptor agonist and 5-HT(2c) antagonist, and is able to restore the internal clock, which is profoundly disturbed in depression, thus being efficacious in major depressive disorders.
In addition, homozygous or hemizygous carriers of the 5-HT2C Ser allele were 12 times more likely to have major depressive illness than homozygous or hemizygous carriers of the 5-HT2C Cys allele.
Studies on mice revealed that 5-HT2C pre-mRNA editing is regulated in a serotonin-dependent manner, and postmortem studies on brain tissues of patients with schizophrenia and major depression found distinct site-specific alterations of this editing in the prefrontal cortex, a brain region expressing a large number of differently edited 5-HT2C mRNA isoforms.
These findings are in accordance with the previous findings, and suggest that altered RNA editing of HTR2C may have some significance in major depression and suicide.
An examination of the efficiencies of RNA editing of the 5-HT(2C)R in prefrontal cortex of control individuals vs. subjects diagnosed with schizophrenia or major depressive disorder revealed no significant differences in RNA editing among the three populations.