Shared co-expression networks in frontal cortex of the normal aged brain and schizophrenia

Abstract

Previous studies on the brain of people with schizophrenia have identified structural changes and gene expression changes, suggesting that brain aging maybe accelerated in people with schizophrenia. To better characterize gene expression profiles in schizophrenia and in the aged population we constructed co-expression networks using RNA-Seq data from frontal cortex. The first data set analysed was from 62 subjects with schizophrenia and 51 unaffected controls ranging in age from 19 to 63 years. The second separate data set was from normal control individuals ranging in age from 29 to 106 years. In the first data set, we found two co-expression modules significantly associated with schizophrenia. One was a downregulated co-expression module enriched for neuron function related genes and the other was an upregulated immune/inflammation-related module. In the second data set of normal individuals, we found seven co-expression modules significantly correlated with age. A comparison of the co-expression modules from the two data sets revealed a significant consensus in nodes associated with schizophrenia and those associated with normal aging. The results indicate that a co-expression module related to neuronal function is downregulated and an immune/inflammation related co-expression module is upregulated, and associated with cells of the blood vessels, in both schizophrenia and in normal aging. This finding adds further support to the hypothesis that there may be accelerated brain aging in schizophrenia. (C) 2018 Elsevier B.V. All rights reserved.