Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes

Major depressive disorder (MDD) is a common, heterogenous, and potentially serious psychiatric illness. Diverse brain cell types have been implicated in MDD etiology. Significant sexual differences exist in MDD clinical presentation and outcome, and recent evidence suggests different molecular bases...

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Published in:Nature communications Vol. 14; no. 1; pp. 2912 - 18
Main Authors: Maitra, Malosree, Mitsuhashi, Haruka, Rahimian, Reza, Chawla, Anjali, Yang, Jennie, Fiori, Laura M., Davoli, Maria Antonietta, Perlman, Kelly, Aouabed, Zahia, Mash, Deborah C., Suderman, Matthew, Mechawar, Naguib, Turecki, Gustavo, Nagy, Corina
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 22.05.2023
Nature Publishing Group
Nature Portfolio
Subjects:
38
38/91
631/337/2019
631/378
631/378/1689/1414
Astrocytes
Brain
Brain - metabolism
Clusters
Depression - genetics
Depressive Disorder, Major - genetics
Depressive Disorder, Major - metabolism
Female
Females
Gender differences
Gene expression
Gene sequencing
Genes
Glial stem cells
Humanities and Social Sciences
Humans
Interneurons
Male
Males
Mental depression
Microglia
multidisciplinary
Parvalbumin
Prefrontal cortex
Prefrontal Cortex - metabolism
Science
Science (multidisciplinary)
Sex differences
Transcriptome - genetics
Transcriptomes
Transcriptomics
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Major depressive disorder (MDD) is a common, heterogenous, and potentially serious psychiatric illness. Diverse brain cell types have been implicated in MDD etiology. Significant sexual differences exist in MDD clinical presentation and outcome, and recent evidence suggests different molecular bases for male and female MDD. We evaluated over 160,000 nuclei from 71 female and male donors, leveraging new and pre-existing single-nucleus RNA-sequencing data from the dorsolateral prefrontal cortex. Cell type specific transcriptome-wide threshold-free MDD-associated gene expression patterns were similar between the sexes, but significant differentially expressed genes (DEGs) diverged. Among 7 broad cell types and 41 clusters evaluated, microglia and parvalbumin interneurons contributed the most DEGs in females, while deep layer excitatory neurons, astrocytes, and oligodendrocyte precursors were the major contributors in males. Further, the Mic1 cluster with 38% of female DEGs and the ExN10_L46 cluster with 53% of male DEGs, stood out in the meta-analysis of both sexes. Sex differences in brain transcriptomics have unknown cell type specificity. Here, authors show concordant cortical transcriptomic patterns in depression within individual cell types between sexes, but distinctly affected top cell types and genes.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-38530-5