ArticleBiology of sex differences2013
Sex chromosome complement regulates expression of mood-related genes.
Article in Biology of sex differences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Global burden of antenatal depression and its association with adverse birth outcomes: an umbrella review.BMC public health · 2020Pooled it
- Women's musculoskeletal health: insights from the 2024 National Academies of Sciences, Engineering, and Medicine report on chronic conditions.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- Unraveling the Complex Interplay Between Neuroinflammation and Depression: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Sex differences and hormonal regulation of metabotropic glutamate receptor synaptic plasticity.International review of neurobiology · 2023Review
- Large-Scale Transcriptomics Studies Provide Insight Into Sex Differences in Depression.Biological psychiatry · 2022Review
- Sex Differences in Depression Caused by Early Life Stress and Related Mechanisms.Frontiers in neuroscience · 2022Review
- Sex-Specific Brain Transcriptional Signatures in Human MDD and Their Correlates in Mouse Models of Depression.Frontiers in behavioral neuroscience · 2022Review
- Who Is Suffering from the "Corona Blues"? An Analysis of the Impacts of the COVID-19 Pandemic on Depression and Its Implications for Health Policy.International journal of environmental research and public health · 2021Article
- Sex differences in anxiety and depression: circuits and mechanisms.Nature reviews. Neuroscience · 2021Review
- In search of sex-related mediators of affective illness.Biology of sex differences · 2021Review
- Anxiety and Its Associated Factors During the Initial Phase of the COVID-19 Pandemic in Indonesia.Frontiers in psychiatry · 2021Article
- Contributions of Sex Chromosomes and Gonadal Hormones to the Male Bias in a Maternal Antibody-Induced Model of Autism Spectrum Disorder.Frontiers in neurology · 2021Article
- The effects of early life stress on motivated behaviors: A role for gonadal hormones.Neuroscience and biobehavioral reviews · 2020Review
- Four Core Genotypes and XY* mouse models: Update on impact on SABV research.Neuroscience and biobehavioral reviews · 2020Review
- Sexual Differentiation and Substance Use: A Mini-Review.Endocrinology · 2020Review
- Sex differences in adult mood and in stress-induced transcriptional coherence across mesocorticolimbic circuitry.Translational psychiatry · 2020Article
- Putative Epigenetic Biomarkers of Stress in Red Blood Cells of Chickens Reared Across Different Biomes.Frontiers in genetics · 2020Article
- Sex Differences in Vulnerability and Resilience to Stress Across the Life Span.Biological psychiatry · 2019Review
- Sex-Specific Effects of Stress on Mood-Related Gene Expression.Molecular neuropsychiatry · 2019Article
- Sex differences in incentive motivation and the relationship to the development and maintenance of alcohol use disorders.Physiology & behavior · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStudies on major depressive and anxiety disorders suggest dysfunctions in brain corticolimbic circuits, including altered gamma-aminobutyric acid (GABA) and modulatory (serotonin and dopamine) neurotransmission. Interestingly, sexual dimorphisms in GABA, serotonin, and dopamine systems are also reported. Understanding the mechanisms behind these sexual dimorphisms may help unravel the biological bases of the heightened female vulnerability to mood disorders. Here, we investigate the contribution of sex-related factors (sex chromosome complement, developmental gonadal sex, or adult circulating hormones) to frontal cortex expression of selected GABA-, serotonin-, and dopamine-related genes.
methodsAs gonadal sex is determined by sex chromosome complement, the role of sex chromosomes cannot be investigated individually in humans. Therefore, we used the Four Core Genotypes (FCG) mouse model, in which sex chromosome complement and gonadal sex are artificially decoupled, to examine the expression of 13 GABA-related genes, 6 serotonin- and dopamine-related genes, and 8 associated signal transduction genes under chronic stress conditions. Results were analyzed by three-way ANOVA (sex chromosome complement × gonadal sex × circulating testosterone). A global perspective of gene expression changes was provided by heatmap representation and gene co-expression networks to identify patterns of transcriptional activities related to each main factor.
resultsWe show that under chronic stress conditions, sex chromosome complement influenced GABA/serotonin/dopamine-related gene expression in the frontal cortex, with XY mice consistently having lower gene expression compared to XX mice. Gonadal sex and circulating testosterone exhibited less pronounced, more complex, and variable control over gene expression. Across factors, male conditions were associated with a tightly co-expressed set of signal transduction genes.
conclusionsUnder chronic stress conditions, sex-related factors differentially influence expression of genes linked to mood regulation in the frontal cortex. The main factor influencing expression of GABA-, serotonin-, and dopamine-related genes was sex chromosome complement, with an unexpected pro-disease effect in XY mice relative to XX mice. This effect was partially opposed by gonadal sex and circulating testosterone, although all three factors influenced signal transduction pathways in males. Since GABA, serotonin, and dopamine changes are also observed in other psychiatric and neurodegenerative disorders, these findings have broader implications for the understanding of sexual dimorphism in adult psychopathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.