Abstract
Objectives. mRNA for serotonin 2C receptor (5-HT2CR) undergoes editing which results in numerous isoforms. More highly edited isoforms exhibit decreased function. We recently found greater 5-HT2CR 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 (MDDSuic and MDDNoSuic) and non-suicide NC. Methods. mRNA editing was assessed in prefrontal cortex of 24 MDDSuic, 21 MDDNoSuic, and 56 NC using next generation sequencing. mRNA expression of 5-HT2CR and editing enzymes (ADAR1-2) was assessed by real-time PCR. Results. Editing was lower in MDDNoSuic than in MDDSuic, which did not differ from NC. No differences in the 5-HT2CR or ADAR1 expression were detected. ADAR2 expression was higher in NC than in MDD subjects, but did not differ between MDDNoSuic and MDDSuic. Conclusions. Our findings suggest the presence of two factors associated with 5-HT2CR 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.
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.