Serotonin 2c receptor RNA editing in major depression and suicide

mRNA for serotonin 2C receptor (5-HT(2C)R) undergoes editing which results in numerous isoforms. More highly edited isoforms exhibit decreased function. We recently found greater 5-HT(2C)R editing in suicide victims with prior bipolar disorder (BPD) or schizophrenia (SZ) compared with non-suicide patients and normal controls (NC). This study compares suicides and non-suicides with major depressive disorder (MDD(Suic) and MDD(NoSuic)) and non-suicide NC.

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.

Editing was lower in MDD(NoSuic) than in MDD(Suic), which did not differ from NC. No differences in the 5-HT(2C)R or ADAR1 expression were detected. ADAR2 expression was higher in NC than in MDD subjects, but did not differ between MDD(NoSuic) and MDD(Suic).

Our findings suggest the presence of two factors associated with 5-HT(2C)R editing. One factor, which probably stems from decreased ADAR2 expression, is linked to MDD and is associated with less editing. The other, seen also in our previous study of suicide in BP and SZ, is linked to suicide alone and is associated with more editing and, therefore, less receptor function.