title: Transcriptome sequencing of the anterior cingulate in bipolar disorder: dysregulation of G protein-coupled receptors.
abstract: OBJECTIVE
  Gene expression dysregulation in the brain has been associated with bipolar disorder through candidate gene and microarray expression studies, but questions remain about isoform-specific dysregulation and the role of noncoding RNAs whose importance in the brain has been suggested recently but not yet characterized for bipolar disorder.
  
  
  METHODS
  The authors used RNA sequencing, a powerful technique that captures the complexity of gene expression, in postmortem tissue from the anterior cingulate cortex from 13 bipolar disorder case subjects and 13 matched comparison subjects. Differential expression was computed, and a global pattern of downregulation was detected, with 10 transcripts significant at a false discovery rate ≤5%. Importantly, all 10 genes were also replicated in an independent RNA sequencing data set (N=61) from the anterior cingulate cortex.
  
  
  RESULTS
  Among the most significant results were genes coding for class A G protein-coupled receptors: SSTR2 (somatostatin receptor 2), CHRM2 (cholinergic receptor, muscarinic 2), and RXFP1 (relaxin/insulin-like family peptide receptor 1). A gene ontology analysis of the entire set of differentially expressed genes pointed to an overrepresentation of genes involved in G protein-coupled receptor regulation. The top genes were followed up by querying the effect of treatment with mood stabilizers commonly prescribed in bipolar disorder, which showed that these drugs modulate expression of the candidate genes.
  
  
  CONCLUSIONS
  By using RNA sequencing in the postmortem bipolar disorder brain, an interesting profile of G protein-coupled receptor dysregulation was identified, several new bipolar disorder genes were indicated, and the noncoding transcriptome in bipolar disorder was characterized. These findings have important implications with regard to fine-tuning our understanding of the bipolar disorder brain, as well as for identifying potential new drug target pathways.
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Cruceanu
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Powell Patrick Cheng
authors.initials: PP
authors.lastname: Tan
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Sanja
authors.initials: S
authors.lastname: Rogic
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lopez
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Susana Gabriela
authors.initials: SG
authors.lastname: Torres-Platas
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Carolina O
authors.initials: CO
authors.lastname: Gigek
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Alda
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlidis
authors.affiliation: From the Department of Psychiatry, McGill University, Montreal, Quebec, Canada; the McGill Group for Suicide Studies and Douglas Research Institute, Montreal, Quebec, Canada; the Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; the Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, Vancouver, British Columbia Canada; and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000494:pharmacology; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism; D002220:Carbamazepine / Q000494:pharmacology; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018020:Lithium Compounds / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics*; D018000:Receptors, Peptide / Q000187:drug effects / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D018692:Antimanic Agents; C487078:CHRM2 protein, human; D018020:Lithium Compounds; D012333:RNA, Messenger; C417543:RXFP1 protein, human; D043585:Receptor, Muscarinic M2; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D002220:Carbamazepine; D014635:Valproic Acid