Background: High-throughput expression analyses of postmortem brain tissue have been widely used to study bipolar disorder and schizophrenia. However, despite the extensive efforts, no consensus has emerged as to the functional interpretation of the findings. We hypothesized that incorporating information on cell type-specific expression would provide new insights.
Methods: We reanalyzed 15 publicly available bulk tissue expression datasets on schizophrenia and bipolar disorder, representing various brain regions from eight different cohorts of subjects (unique subjects: 332 control, 129 bipolar disorder, 341 schizophrenia). We studied changes in the expression profiles of cell type marker genes and evaluated whether these expression profiles could serve as surrogates for relative abundance of their corresponding cells.
Results: In both bipolar disorder and schizophrenia, we consistently observed an increase in the expression profiles of cortical astrocytes and a decrease in the expression profiles of fast-spiking parvalbumin interneurons. No changes in astrocyte expression profiles were observed in subcortical regions. Furthermore, we found that many of the genes previously identified as differentially expressed in schizophrenia are highly correlated with the expression profiles of astrocytes or fast-spiking parvalbumin interneurons.
Conclusions: Our results indicate convergence of transcriptome studies of schizophrenia and bipolar disorder on changes in cortical astrocytes and fast-spiking parvalbumin interneurons, providing a unified interpretation of numerous studies. We suggest that these changes can be attributed to alterations in the relative abundance of the cells and are important for understanding the pathophysiology of the disorders.
Keywords: Cell types; Cortex; Gene expression; Meta-analysis; Mitochondria; Psychiatric disorders.
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