Meta-Analysis of Transcriptomic Data of Dorsolateral Prefrontal Cortex and of Peripheral Blood Mononuclear Cells Identifies Altered Pathways in Schizophrenia

Genes (Basel). 2020 Apr 3;11(4):390. doi: 10.3390/genes11040390.

Abstract

Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive and negative symptoms, including cognitive dysfunction, decline in motivation, delusion and hallucinations. Antipsychotic agents are currently the standard of care treatment for SCZ. However, only about one-third of SCZ patients respond to antipsychotic medications. In the current study, we have performed a meta-analysis of publicly available whole-genome expression datasets on Brodmann area 46 of the brain dorsolateral prefrontal cortex in order to prioritize potential pathways underlying SCZ pathology. Moreover, we have evaluated whether the differentially expressed genes in SCZ belong to specific subsets of cell types. Finally, a cross-tissue comparison at both the gene and functional level was performed by analyzing the transcriptomic pattern of peripheral blood mononuclear cells of SCZ patients. Our study identified a robust disease-specific set of dysfunctional biological pathways characterizing SCZ patients that could in the future be exploited as potential therapeutic targets.

Keywords: MAP kinases; prefrontal cortex; schizophrenia; transcriptomic meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / therapeutic use
  • Brain / metabolism*
  • Brain / pathology
  • Brain Mapping
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Genome, Human / drug effects
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / pathology
  • Signal Transduction / drug effects
  • Transcriptome / genetics*

Substances

  • Antipsychotic Agents