Molecular programs underlying differences in the expression of mood disorders in males and females
Abstract
Major depressive disorder (MDD) is a sexually dimorphic disease. This sexual dimorphism is believed to result from sex-specific molecular alterations affecting functional pathways regulating the capacity of males and females to cope with daily life stress differently. Transcriptional changes associated with epigenetic alterations have been observed in the brain of males and females with depression. Similar changes have also been reported in different animal models of stress-induced depressive-like behaviors. Although the vast majority of work has been performed in males, a series of genome wide and gene candidate studies have assessed the extent of these molecular alterations in the brain of males and females revealing sex-specific changes in critical systems controlling mood. This review examines the current literature and summarizes the recent findings exploring the sexual dimorphism underlying the molecular mechanism involved in the expression of MDD.
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Transcriptomic and methylomic overlap between males and females is limited-often below 10% and, in some cases, directionally opposite.
“transcriptomic and methylomic overlap between males and females is limited—often below 10% and, in some cases, directionally opposite—indicating a molecular basis for sexual dimorphism (Mena and Benoit, 2019).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Mena and Benoit, 2019
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Lv, L.-Z., Wang, Z.-D., Ren, J.-J., Li, L.-H., Liu, X.-B., Li, J.-L., Zhu, H., Jiang, B., Han, Y.-P., Zhou, X.-M., et al. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2025.1722453 · Cited by 7 · see citing works
- Authors
- Mena, F., & Benoit, L.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 1719
- Pages
- 89-103
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2945575224
- Cited by
- 9
- References
- 36
- Citations by year
- 2026: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3
- FWCI
- 0.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Canadian HIV Trials Network, Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- major depressive disorder, sexual dimorphism, sex differences, mood disorders, epigenetic modifications, gene expression changes, stress-induced depression, sex-specific gene expression
- MeSH terms
- Animals, Depression, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Male, Sex Characteristics, Sex Factors, Stress, Psychological, Mood Disorders
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