Interactive neuroinflammation pathways and transcriptomics-based identification of drugs and chemical compounds for schizophrenia.

Objectives: Schizophrenia is a psychiatric disorder affecting 1% of the population. Accumulating evidence indicates that neuroinflammation is involved in the pathology of these disorders by altering neurodevelopmental processes and specifically affecting glutamatergic signalling and astrocytic functioning. The aim of this study was to curate interactive biological pathways involved in schizophrenia for the identification of novel pharmacological targets implementing pathway, gene ontology, and network analysis.

Methods: Neuroinflammatory pathways were created using PathVisio and published in WikiPathways. A transcriptomics dataset, originally created by Narla et al. was selected for data visualisation and analysis. Transcriptomics data was visualised within pathways and networks, extended with transcription factors, pathways, and drugs. Network hubs were determined based on degrees of connectivity.

Results: Glutamatergic, immune, and astrocytic signalling as well as extracellular matrix reorganisation were altered in schizophrenia while we did not find an effect on the complement system. Pharmacological agents that target the glutamate receptor subunits, inflammatory mediators, and metabolic enzymes were identified.

Conclusions: New neuroinflammatory pathways incorporating the extracellular matrix, glutamatergic neurons, and astrocytes in the aetiology of schizophrenia were established. Transcriptomics based network analysis provided novel targets, including extra-synaptic glutamate receptors, glutamate transporters and extracellular matrix molecules that can be evaluated for therapeutic strategies.