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

• Published in: Genes Vol. 11; no. 4; p. 390
• Main Authors: Petralia, Maria Cristina, Ciurleo, Rosella, Saraceno, Andrea, Pennisi, Manuela, Basile, Maria Sofia, Fagone, Paolo, Bramanti, Placido, Nicoletti, Ferdinando, Cavalli, Eugenio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.04.2020; MDPI
• Subjects: Antipsychotic Agents - therapeutic use; Antipsychotics; Brain - metabolism; Brain - pathology; Brain Mapping; Brodmann's area; Cognitive ability; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - genetics; Cognitive Dysfunction - pathology; Datasets; Emotional behavior; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation - drug effects; Genome, Human - drug effects; Genomes; Hallucinations; Homeostasis; Humans; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Male; Medical Subject Headings-MeSH; Mental disorders; Meta-analysis; Motivation; Ontology; Peripheral blood mononuclear cells; Prefrontal cortex; Prefrontal Cortex - metabolism; Prefrontal Cortex - pathology; Psychotropic drugs; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - genetics; Schizophrenia - pathology; Signal Transduction - drug effects; Software; Statistical analysis; Therapeutic applications; Transcriptome - genetics; transcriptomic meta-analysis; schizophrenia; prefrontal cortex; MAP kinases
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes11040390

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.