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Transcriptional dissection of symptomatic profiles across the brain of men and women with depression

Author

Listed:
  • Samaneh Mansouri

    (CERVO Brain Research Centre
    Université Laval)

  • André M. Pessoni

    (CERVO Brain Research Centre
    Université Laval)

  • Arturo Marroquín-Rivera

    (CERVO Brain Research Centre
    Université Laval)

  • Eric M. Parise

    (Icahn School of Medicine at Mount Sinai, New York)

  • Carol A. Tamminga

    (The University of Texas Southwestern Medical Center)

  • Gustavo Turecki

    (Douglas Mental Health University Institute
    McGill University)

  • Eric J. Nestler

    (Icahn School of Medicine at Mount Sinai, New York)

  • Ting-Huei Chen

    (CERVO Brain Research Centre
    Laval University)

  • Benoit Labonté

    (CERVO Brain Research Centre
    Université Laval)

Abstract

Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the associations between these structures and the expression of MDD remain highly sex specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes were also identified. Together, our findings suggest that the expression of distinct MDD symptom domains associates with sex-specific transcriptional structures across brain regions.

Suggested Citation

  • Samaneh Mansouri & André M. Pessoni & Arturo Marroquín-Rivera & Eric M. Parise & Carol A. Tamminga & Gustavo Turecki & Eric J. Nestler & Ting-Huei Chen & Benoit Labonté, 2023. "Transcriptional dissection of symptomatic profiles across the brain of men and women with depression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42686-5
    DOI: 10.1038/s41467-023-42686-5
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    References listed on IDEAS

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    1. Zhang Bin & Horvath Steve, 2005. "A General Framework for Weighted Gene Co-Expression Network Analysis," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 4(1), pages 1-45, August.
    2. Peter Langfelder & Rui Luo & Michael C Oldham & Steve Horvath, 2011. "Is My Network Module Preserved and Reproducible?," PLOS Computational Biology, Public Library of Science, vol. 7(1), pages 1-29, January.
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