Unraveling Psychiatric Disorders through Neural Single-Cell Transcriptomics Approaches

Abstract

The development of single-cell and single-nucleus transcriptome technologies is enabling the unraveling of the molecular and cellular heterogeneity of psychiatric disorders. The complexity of the brain and the relationships between different brain regions can be better understood through the classification of individual cell populations based on their molecular markers and transcriptomic features. Analysis of these unique cell types can explain their involvement in the pathology of psychiatric disorders. Recent studies in both human and animal models have emphasized the importance of transcriptome analysis of neuronal cells in psychiatric disorders but also revealed critical roles for non-neuronal cells, such as oligodendrocytes and microglia. In this review, we update current findings on the brain transcriptome and explore molecular studies addressing transcriptomic alterations identified in human and animal models in depression and stress, neurodegenerative disorders (Parkinson’s and Alzheimer’s disease), schizophrenia, opioid use disorder, and alcohol and psychostimulant abuse. We also comment on potential future directions in single-cell and single-nucleus studies.

The Genomic Intersection of Oligodendrocyte Dynamics in Schizophrenia and Aging Unravels Novel Pathological Mechanisms and Therapeutic Potentials

“…Overall, further histological studies are needed to describe the changes in cellular quantification across different brain compartments. Nevertheless, recent transcriptomic studies at the single cell level have increasingly contributed to our understanding of aging processes in human and rodent OLs [23,24,59,60], whilst for schizophrenia, such studies are currently limited to neurons or astrocytes for the time being [61][62][63]. Moreover, due to the vast regional and cell-specific complexity of the human brain, a comprehensive transcriptional overview of the detrimental changes occurring during aging is still lacking.…”