Immune involvement in neuropsychiatric disorders: Insights from single-cell transcriptomic studies

Area of Science:

• Neuroscience
• Immunology
• Genomics

Background:

• Neuropsychiatric disorders present research and treatment challenges due to heterogeneity and unknown biological mechanisms.
• Bulk RNA sequencing (RNA-seq) lacks cell-type specificity and cannot detect rare cell populations.
• Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) offer single-cell resolution for transcriptomic profiling.

Purpose of the Study:

• To review recent findings from sc/snRNA-seq studies on immune mechanisms in psychiatric and neurological disorders.
• To highlight the advantages of sc/snRNA-seq over bulk RNA-seq in resolving cell-type-specific signals.
• To propose an integrated approach combining bulk and single-cell RNA sequencing.

Main Methods:

• Review of recent literature utilizing sc/snRNA-seq.
• Analysis of immune-related findings in various psychiatric disorders (schizophrenia, bipolar disorder, MDD, ASD, ADHD).
• Analysis of immune-related findings in neurological conditions (Alzheimer's, Parkinson's, DLB, MS, anti-NMDA receptor encephalitis).

Main Results:

• sc/snRNA-seq have uncovered significant immunological alterations in a wide spectrum of neuropsychiatric and neurological disorders.
• These methods resolve cell types, overcoming the averaging effects inherent in bulk RNA-seq.
• Despite advancements, challenges remain in single-cell transcriptomic analysis.

Conclusions:

• sc/snRNA-seq are powerful tools for dissecting immune-related mechanisms in complex brain disorders.
• Integrating bulk RNA-seq with sc/snRNA-seq can address current limitations and provide a more comprehensive understanding.
• This integrated roadmap aims to mitigate gaps in current transcriptomic analyses for neuropsychiatric and neurological research.