Abstract
The Clinical Brain Disorders Branch of the Intramural Research Program at the National Institutes of Health assembled a large collection of frozen post-mortem human brains from individuals diagnosed with schizophrenia, or other psychiatric diagnoses as well as matched control individuals, collected Illumina HumanHT-12 v4 expression array data from dorsolateral prefrontal cortex (DLPFC) of those brains, and deposited the data at dbGaP (Study ID: phs000979). We report an analysis of the data from the 188 adult schizophrenics and 206 adult controls in that cohort. Transcripts from 635 genes are differentially expressed in the schizophrenics as compared to the controls at a level of statistical significance which survived Bonferroni correction. Seventeen of those genes are differentially expressed at a level of statistical significance less than 10-8 after Bonferroni correction. WGCNA analysis using gene module eigengenes divided the schizophrenics into two groups, “type 1” and “type 2”. There are 2,253 genes differentially expressed in the DLPFC of type 2 schizophrenics at a level of statistical significance which survives Bonferroni correction. Of them 160 have P-values less than 10-15 after Bonferroni correction. In the type 1 schizophrenics however, only 13 genes are differentially expressed in the DLPFC and of those 13, only one is also differentially expressed in the type 2 schizophrenics. This striking difference in their DLPFC transcriptomes emphasizes the fundamental biologic difference between these two groups of patients. The fact that only a few genes are differentially expressed in the DLPFC of type 1 schizophrenics while over two thousand are differentially expressed in the type 2 schizophrenics suggests a testable hypothesis. Although the DLPFC is clearly abnormal in the type 2 schizophrenics, for the type 1 schizophrenics the physiologically significant pathology may be elsewhere, perhaps in the superior temporal or cingulate gyri.