title: Region-specific alterations of A-to-I RNA editing of serotonin 2c receptor in the cortex of suicides with major depression.
abstract: Brain region-specific abnormalities in serotonergic transmission appear to underlie suicidal behavior. Alterations of RNA editing on the serotonin receptor 2C (HTR2C) pre-mRNA in the brain of suicides produce transcripts that attenuate 5-HT2CR signaling by impairing intracellular G-protein coupling and subsequent intracellular signal transduction. In brain, the distribution of RNA-editing enzymes catalyzing deamination (A-to-I modification) shows regional variation, including within the cerebral cortex. We tested the hypothesis that altered pre-mRNA 5-HT2CR receptor editing in suicide is region-specific. To this end, we investigated the complete 5-HT2CR mRNA-editing profile in two architectonically distinct cortical areas involved in mood regulation and decision-making in a clinically well-characterized cohort of age- and sex-matched non-psychiatric drug-free controls and depressed suicides. By using an original biochemical detection method, that is, capillary electrophoresis single-stranded conformational polymorphism (CE-SSCP), we corroborated the 5-HT2CR mRNA-editing profile previously described in the dorsolateral prefrontal cortex (Brodmann area 9 (BA9)). Editing of 5-HT2CR mRNA displayed clear regional difference when comparing dorsolateral prefrontal cortex (BA9) and anterior cingulate cortex (BA24). Compared with non-psychiatric control individuals, alterations of editing levels of 5-HT2CR mRNA were detected in both cortical areas of depressed suicides. A marked increase in editing on 5-HT2CR was especially observed in the anterior cingulate cortex in suicides, implicating this cortical area in suicide risk. The results suggest that region-specific changes in RNA editing of 5-HT2CR mRNA and deficient receptor function likely contribute to the etiology of major depressive disorder or suicide.
authors: ALCEDIAG/CNRS Sys2Diag FRE3690, Biological Complex System Modeling and Engineering for Diagnosis, Cap delta/Parc Euromédecine, Montpellier, France.
authors: D
authors: D
authors: Weissmann
authors: ALCEDIAG/CNRS Sys2Diag FRE3690, Biological Complex System Modeling and Engineering for Diagnosis, Cap delta/Parc Euromédecine, Montpellier, France.
authors: S
authors: S
authors: van der Laan
authors: Division of Molecular Imaging and Neuropathology, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors: M D
authors: MD
authors: Underwood
authors: ALCEDIAG/CNRS Sys2Diag FRE3690, Biological Complex System Modeling and Engineering for Diagnosis, Cap delta/Parc Euromédecine, Montpellier, France.
authors: N
authors: N
authors: Salvetat
authors: L
authors: L
authors: Cavarec
authors: L
authors: L
authors: Vincent
authors: ALCEDIAG/CNRS Sys2Diag FRE3690, Biological Complex System Modeling and Engineering for Diagnosis, Cap delta/Parc Euromédecine, Montpellier, France.
authors: F
authors: F
authors: Molina
authors: Division of Molecular Imaging and Neuropathology, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors: J J
authors: JJ
authors: Mann
authors: Division of Molecular Imaging and Neuropathology, Columbia University College of Physicians and Surgeons, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors: V
authors: V
authors: Arango
authors: ALCEDIAG/CNRS Sys2Diag FRE3690, Biological Complex System Modeling and Engineering for Diagnosis, Cap delta/Parc Euromédecine, Montpellier, France.
authors: J F
authors: JF
authors: Pujol
mesh_terms: D000293:Adolescent; D000328:Adult; D001344:Autopsy; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D003641:Deamination / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics*; D019075:Electrophoresis, Capillary; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D017397:Prefrontal Cortex / Q000378:metabolism*; D017393:RNA Editing / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D016728:Self-Injurious Behavior / Q000235:genetics*; D013405:Suicide; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C