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

Malosree Maitra, Haruka Mitsuhashi, Reza Rahimian, Anjali Chawla, Jennie Yang, Laura M. Fiori, Maria Antonietta Davoli, Kelly Perlman, Zahia Aouabed, Deborah C. Mash, Matthew Suderman, Naguib Mechawar, Gustavo Turecki () and Corina Nagy ()
Additional contact information
Malosree Maitra: Douglas Institute
Haruka Mitsuhashi: Douglas Institute
Reza Rahimian: Douglas Institute
Anjali Chawla: Douglas Institute
Jennie Yang: Douglas Institute
Laura M. Fiori: Douglas Institute
Maria Antonietta Davoli: Douglas Institute
Kelly Perlman: Douglas Institute
Zahia Aouabed: Douglas Institute
Deborah C. Mash: Nova Southeastern University
Matthew Suderman: University of Bristol
Naguib Mechawar: Douglas Institute
Gustavo Turecki: Douglas Institute
Corina Nagy: Douglas Institute

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-38530-5

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