Differential activation of immune/inflammatory response-related co-expression modules in the hippocampus across the major psychiatric disorders

Abstract

The Stanley Neuropathology Consortium Integrative Database (SNCID, http://sncid.stanleyresearch.org) is a data -mining tool that includes 379 neuropathology data sets from hippocampus, as well as RNA-Seq data measured in 15 well -matched cases in each of four groups: schizophrenia, bipolar disorder (BPD), major depression (MD) and unaffected controls. We analyzed the neuropathology data from the hippocampus to identify those abnormalities that are shared between psychiatric disorders and those that are specific to each disorder. Of the 379 data sets, 20 of them showed a significant abnormality in at least one disorder as compared with unaffected controls. GABAergic markers and synaptic proteins were mainly abnormal in schizophrenia and the two mood disorders, respectively. Two immune/inflammation-related co -expression modules built from RNA-seq data from both schizophrenia and controls combined were associated with disease status, as well as negatively correlated with the GABAergic markers. The correlation between immune -related modules and schizophrenia was replicated using microarray data from an independent tissue collection. Immune/inflammation-related co -expression modules were also built from RNA-seq data from BPD cases or from MD cases but were not preserved when using data from control cases. Moreover, there was no overlap in the genes that comprise the immune/inflammation response -related modules across the different disorders. Thus, there appears to be differential activation of the immune/inflammatory response, as determined by co -expression of genes, which is associated with the major psychiatric disorders and which is also associated with the abnormal neuropathology in the disorders.