Gene Expression Profile of G Protein Coupled Receptor Related signaling Pathways in Mood Disorder

Hiroaki Tomita; Simon J. Evans; Jun Z. Li; Prabhakara V. Choudary; Marquis P. Vawter; Fan Meng; Ling Shao; Charles R. Neal; John D.H.Stead; David M. Walsh; Mary E. Atz; Kevin M. Overman; Richard M. Myers; Edward G. Jones; Stanley J. Watson; Huda Akil; William E. Bunney
Joint meeting of the Japanese Society of Biological Psychiatry (JSBP) and the Japanese Society of Neuropsychopharmacology (JSNP). 2005.


Evidence supports altered G protein coupled receptor (GPCR) related neurotransmitter system, including monoamines and neuropeptides in the central nervous system of patients with bipolar disorder (BPD) and major depressive disorder (MDD). Increasing evidence also supports dysfunction in intracellular downstream signaling events of GPCRs, including cAMP signaling, phosphatidylinositol signaling, and mitogen-activated protein kinase (MAPK) signaling in the brain of patients with BPD and MDD. We used Affymetrix GeneChip to evaluate gene expression patterns related to GPCR signaling in the human postmortem dorsolateral prefrontal, anterior cingulate, and cerebellar cortices of patients with BPD and MDD compared to those of healthy controls. Reliability of the microarray data were evaluated based on consistency between experimental duplicates and quantitative RT-PCR. Gene expression relevant to neuropeptide system was dominantly dysregulated in BPD. Genes involved in cAMP and phosphatidylinositol signaling pathways tended to be upregulated in BPD, while down regulated in MDD. These differentially expressed genes in GPCR and downstream signaling pathways may be involved in the pathogeneses of BPD and MDD.