Abstract

Expression of glutamate signaling, growth factor, and astrocyte-associated genes are altered in the locus coeruleus of patients with major depressive disorder (MD) but not bipolar disorder (BP).

R. BERNARD; I. A. KERMAN; R. C. THOMPSON; E. G. JONES; W. E. BUNNEY; R. M. MYERS; H. AKIL; S. WATSON
Society for Neuroscience. 2009.

Abstract

The locus coeruleus (LC) is the major source for noradrenergic innervation of the brain. Dysregulation of noradrenergic neurotransmission has been implicated in psychiatric disorders. To understand the pathophysiological changes that occur in the LC we have used postmortem brains of patients with BP (N=6), MD (N=12) and psychiatrically-normal subjects (N=9) to contrast their LC gene expression profiles. Total RNA samples from laser capture microdissected LC samples were amplified and probed with Affymetrix oligonucleotide microarrays. Gene expression data were analyzed by ANOVA of the robust multichip average algorithm and by the MAS5calls present call algorithm. Inclusion criteria for altered MD or BP gene expression were set at p⿤0.05 and a minimum of 50% present in control, MD, or BP group. Quantitative real time polymerase chain reaction (qPCR) and in situ hybridization (ISH) were used to confirm selected genes from microarray result. Microarray results show that 8 glutamate signaling genes, 3 growth factor genes, and 5 astrocyte-associated genes were significantly altered in MD but not BP. QPCR confirmed observed microarray changes for 3 glutamate signaling, 2 growth factor genes, and 5 astrocyte-associated genes. The results further extend the existing notion of a primary glial deficit as part of etiology of MD. As reported from some cortical regions, growth factors and glutamate signaling genes show abnormal expression also in the LC of MD patients. For the first time these findings are now documented in a subcortical region supporting the hypothesis of a common global pattern of transcriptional changes in MD.