Serotonin 2c receptor RNA editing in major depression and suicide

Abstract

Objectives. mRNA for serotonin 2C receptor (5-HT_2CR) undergoes editing which results in numerous isoforms. More highly edited isoforms exhibit decreased function. We recently found greater 5-HT_2CR 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. Methods. 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_2CR and editing enzymes (ADAR1-2) was assessed by real-time PCR. Results. Editing was lower in MDD_NoSuic than in MDD_Suic, which did not differ from NC. No differences in the 5-HT_2CR 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. Conclusions. Our findings suggest the presence of two factors associated with 5-HT_2CR 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.

Key words::

• RNA editing
• ADAR
• serotonin receptor
• major depressive disorder
• suicide

Acknowledgements

We are grateful to Mr Scott Navarrett and Ms Katie Lutz for their superb technical assistance and to Dr D.J. Jamison for his help with bioinformatics. Postmortem brain tissue was donated by The Stanley Medical Research Institute courtesy of Drs Michael B. Knable, E. Fuller Torrey, Maree J. Webster, and Robert H. Yolken. This study was supported by VA Merit award to SD, by grants from the Hope for Depression Foundation and the American Foundation for Suicide Prevention (SD), and by the VISN3 Mental Illness Research and Education Clinical Center (MIRECC) (SD, LJS).

Statement of interest

None to declare.