Autism-specific spliceosomal transcriptomic signatures in prefrontal cortex contrasted with bipolar disorder

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Autism spectrum disorder (ASD) and bipolar disorder (BD) are complex neurodevelopmental conditions with overlapping clinical features but distinct underlying molecular mechanisms.
• Understanding these differences is crucial for identifying specific pathways and developing targeted treatments.

Purpose of the Study:

• To identify gene-expression signatures specific to ASD and BD in the prefrontal cortex.
• To compare the disrupted biological processes in ASD and BD.
• To contrast ASD-specific molecular profiles with those of BD.

Main Methods:

• Comparative transcriptomic analysis of postmortem prefrontal cortex RNA-seq datasets from individuals with ASD, BD, and controls.
• Differential gene expression analysis using DESeq2.
• Functional interpretation via Gene Ontology (GO) over-representation analysis, KEGG Gene Set Enrichment Analysis, and gene-concept network visualization.

Main Results:

• ASD samples exhibited 45 differentially expressed genes (DEGs), predominantly downregulated non-coding RNAs (small nuclear and nucleolar RNAs), linked to RNA processing and spliceosome function.
• BD samples showed 12 DEGs, mainly upregulated protein-coding genes, associated with metal ion response, hormone regulation, vascular control, and inflammation (e.g., SERPINA3, CHI3L1).
• No shared DEGs or enriched GO Biological Process terms were found between ASD and BD.

Conclusions:

• The prefrontal cortex exhibits transcriptomic divergence between ASD and BD.
• ASD is characterized by spliceosome dysregulation, while BD involves pathways related to metal ion response, vascular regulation, and inflammation.
• These findings offer a molecular framework for future research into disorder-specific mechanisms in ASD and BD.