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Biol Psychiatry. 2018 Jul 1;84(1):18-27. doi: 10.1016/j.biopsych.2018.01.017. Epub 2018 Feb 19.

Opposite Molecular Signatures of Depression in Men and Women.

Author information

1
Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania; Translational Neuroscience Program, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania. Electronic address: seneyml@upmc.edu.
2
Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
3
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
4
Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania; Translational Neuroscience Program, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania.
5
Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania; Translational Neuroscience Program, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania; Center for Systems Neurogenetics of Addiction, Jackson Laboratory, Bar Harbor, Maine.
6
Department of Computational and Systems Biology, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
7
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Neurobiology of Depression and Aging, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Electronic address: etienne.sibille@camh.ca.

Abstract

BACKGROUND:

Major depressive disorder (MDD) affects women approximately twice as often as men. Women are three times as likely to have atypical depression, with hypersomnia and weight gain. This suggests that the molecular mechanisms of MDD may differ by sex.

METHODS:

To test this hypothesis, we performed a large-scale gene expression meta-analysis across three corticolimbic brain regions: the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and basolateral amygdala (26 men, 24 women with MDD and sex-matched control subjects). Results were further analyzed using a threshold-free approach, Gene Ontology, and cell type-specific analyses. A separate dataset was used for independent validation (13 MDD subjects/sex and 22 control subjects [13 men, 9 women]).

RESULTS:

Of the 706 genes differentially expressed in men with MDD and 882 genes differentially expressed in women with MDD, only 21 were changed in the same direction in both sexes. Notably, 52 genes displayed expression changes in opposite directions between men and women with MDD. Similar results were obtained using a threshold-free approach, in which the overall transcriptional profile of MDD was opposite in men and women. Gene Ontology indicated that men with MDD had decreases in synapse-related genes, whereas women with MDD exhibited transcriptional increases in this pathway. Cell type-specific analysis indicated that men with MDD exhibited increases in oligodendrocyte- and microglia-related genes, while women with MDD had decreases in markers of these cell types.

CONCLUSIONS:

The brain transcriptional profile of MDD differs greatly by sex, with multiple transcriptional changes in opposite directions between men and women with MDD.

KEYWORDS:

Corticolimbic; Depression; Genetics; Meta-analysis; Mood disorders; Sex difference

PMID:
29548746
PMCID:
PMC6014892
[Available on 2019-07-01]
DOI:
10.1016/j.biopsych.2018.01.017

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