title: G protein-linked signaling pathways in bipolar and major depressive disorders.
abstract: The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP), phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD) and bipolar disorder (BPD). This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, "activated" cAMP signaling activity in BPD and "blunted" cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects.
authors.affiliation: Department of Psychiatry and Human Behavior, University of California Irvine, CA, USA ; Department of Biological Psychiatry, Tohoku University Sendai, Japan ; Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine CA, USA.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Department of Psychiatry and Human Behavior, University of California Irvine, CA, USA ; Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine CA, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Ziegler
authors.affiliation: Department of Psychiatry and Human Behavior, University of California Irvine, CA, USA ; Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine CA, USA.
authors.forename: Helen B
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Molecular and Behavioral Neurosciences Institute, University of Michigan Ann Arbor, MI, USA.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Evans
authors.affiliation: Center for Neuroscience, University of California Davis, CA, USA.
authors.forename: Prabhakara V
authors.initials: PV
authors.lastname: Choudary
authors.affiliation: Molecular and Behavioral Neurosciences Institute, University of Michigan Ann Arbor, MI, USA.
authors.forename: Jun Z
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Molecular and Behavioral Neurosciences Institute, University of Michigan Ann Arbor, MI, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Meng
authors.affiliation: Molecular and Behavioral Neurosciences Institute, University of Michigan Ann Arbor, MI, USA.
authors.forename: Manhong
authors.initials: M
authors.lastname: Dai
authors.affiliation: HudsonAlpha Institute for Biotechnology Huntsville, AL, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.affiliation: Molecular and Behavioral Neurosciences Institute, University of Michigan Ann Arbor, MI, USA ; John A. Burns School of Medicine, University of Hawaii Honolulu, HI, USA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Neal
authors.affiliation: Department of Statistics, University of California Berkeley CA, USA.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Speed
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College New York, NY, USA.
authors.forename: Jack D
authors.initials: JD
authors.lastname: Barchas
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University Palo Alto, CA, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
authors.affiliation: Molecular and Behavioral Neurosciences Institute, University of Michigan Ann Arbor, MI, USA.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
authors.affiliation: Molecular and Behavioral Neurosciences Institute, University of Michigan Ann Arbor, MI, USA.
authors.forename: Huda
authors.initials: H
authors.lastname: Akil
authors.affiliation: Center for Neuroscience, University of California Davis, CA, USA.
authors.forename: Edward G
authors.initials: EG
authors.lastname: Jones
authors.affiliation: Department of Psychiatry and Human Behavior, University of California Irvine, CA, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Bunney
authors.affiliation: Department of Psychiatry and Human Behavior, University of California Irvine, CA, USA ; Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine CA, USA.
authors.forename: Marquis P
authors.initials: MP
authors.lastname: Vawter
keywords: G-protein coupled receptor (GPCR); GPR37; GPRC5B; bipolar disorder; cyclic AMP; major depressive disorder; phosphatidylinositol; transcriptome