Abstract

Gene expression profiling reveals unique altered immune gene expression signatures for major depressive disorder, bipolar disorder and schizophrenia.

P. Blandino; J. Li; F. Meng; S.J. Evans; D. Absher; P. Choudary; M.P. Vawter; R.M. Myers; W.E. Bunney; J.D. Barchas; A.F. Schatzberg; E.G. Jones; S.J. Watson; H. Akil
Society for Neuroscience. 2010.

There is accumulating evidence that immune factors are altered in mood and psychiatric disorders. This has led to the hypothesis that immune factors play a role in major depressive disorder (MDD), bipolar disorder (BP) and schizophrenia (SZ). To better understand the role, if any, that immune factors play in MDD, BP and SZ, and to identify which specific immune genes might be critical to these disorders, we took a blended discovery/candidate gene approach and examined the expression of ~2200 immune genes within 10 brain regions: hippocampus (HC), amygdala (AMY), dorsolateral prefrontal cortex (Dlpfc), nucleus accumbens (Nacc), anterior cingulate gyrus (ACg), posterior cingulate gyrus (PCg), subgenual gyrus (SCg), anterior thalamus (aThal), medial thalamus (mThal) and the cerebellum (CB) in post-mortem human brains. Brains were collected as part of the Pritzker Consortium Brain Bank, dissected at -20oC and total RNA was extracted for microarray analysis using an Illumina platform. Brain-wide analysis demonstrated 92 immune genes were commonly altered in MDD, BP and SZ, while 144 immune genes in MDD, 65 in BP and 95 in SZ were uniquely altered for each disorder. Analysis of the 10 regions within each disorder revealed that the greatest number of immune genes with altered expression was in the HC (204) for MDD, Nacc (81) for BP and AMY (132) for SZ. The ACg (11), mThal (14) and CB (20), showed the least altered immune gene expression in MDD, BP and SZ, respectively. Pathway analysis using Ingenuity software suggests that both cellular viability and connectivity between brain regions would be impacted by the altered immune gene expression. These results demonstrate that: 1) there are both unique and shared altered expression of immune genes in MDD, BP and SZ, 2) the degree of altered gene expression and regions affected are disorder specific and 3) a concordant pattern of altered gene expression occurs in a different subset of regions for each disorder. Taken together these results indicate that each of the three major psychiatric disorders carries a unique signature of dysregulated neuroimmune function in the brain.