title: Serotonin 2c receptor RNA editing in major depression and suicide.
abstract: OBJECTIVE
  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.
  
  
  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(2C)R 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(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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: James J Peters Veterans Affairs Medical Center , Bronx, NY , USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lyddon
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwork
authors.forename: Mehdi
authors.initials: M
authors.lastname: Keddache
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
authors.forename: Stella
authors.initials: S
authors.lastname: Dracheva
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics; D000328:Adult; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D017393:RNA Editing / Q000235:genetics*; D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods; D013405:Suicide; D014015:Tissue Banks
chemical_list: D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase