ArticleNature medicine2017
Sex-specific transcriptional signatures in human depression.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 469 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
469 citing papers in PubMed, 4 syntheses or guidelines pooled it, 788 citations in OpenAlex.
- Identification of suicide brain transcriptomic signatures using meta-analysis of multiple cohorts.Translational psychiatry · 2026Pooled it
- Recent developments in omics studies and artificial intelligence in depression and suicide.Translational psychiatry · 2025Pooled it
- Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies.Molecular psychiatry · 2023Pooled it
- Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes.Nature communications · 2023Pooled it
- The role of zinc homeostasis in major depressive disorder: heterogeneous pathological mechanisms and therapeutic implications.Annals of medicine · 2026Review
- Nucleus accumbens neuron subtype translatome signatures in socially stressed females.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- GATA3 drives chronic stress-induced depressive-like behaviors by reducing hippocampal CA3 pyramidal neuronal activity in male mice.Acta pharmacologica Sinica · 2026Article
- Multi-omics characterization of chronic social defeat stress recall-activated nuclei in Arc-GFP mice.Molecular psychiatry · 2026Article
- Extracellular vesicles for liquid biopsy in major depressive disorder: Human evidence and clinical translation.iScience · 2026Review
- Transcriptome changes of disinhibited somatostatin neurons in the medial prefrontal cortex mediating male-specific stress resilience.Research square · 2026Article
- Brain mitochondria as key drivers of cognition and behaviour.Nature reviews. Neuroscience · 2026Review
- Adverse Childhood Experiences, Depression and Subjective Cognitive Decline by Gender: A Moderated Mediation Analysis.Journal of applied gerontology : the official journal of the Southern Gerontological Society · 2026Article
- Multilevel sex-influenced neurobiological signatures of early life adversity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exosomes in depression: mechanistic insights, diagnostic potential, and therapeutic opportunities.Molecular psychiatry · 2026Review
- Transcription-protein dissociation reveals disrupted cellular stress pathways in the prefrontal cortex of depression and schizophrenia subjects.Molecular biomedicine · 2026Article
- VlPAG/DRN Microglia Drive Neuropathic Pain-Induced Depression via a Defined Neuroimmune Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Functional specialization of mPFC-BLA and mPFC-NAc pathways in affective state representation.eLife · 2026Article
- Article
- MicroRNA-148a regulates depressive-like behaviors in mice via the Otx2/Dopaminergic signaling axis.Molecular psychiatry · 2026Article
- Convergent Lower Expression of Redox-Linked Stress-Adaptation and Synaptic-Plasticity Genes in Major Depressive Disorder Across Seven Postmortem dlPFC Cohorts.Antioxidants (Basel, Switzerland) · 2026Article
409 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
28 authors at 6 institutions in 2 countries.
Funding
Abstract
Major depressive disorder (MDD) is a leading cause of disease burden worldwide. While the incidence, symptoms and treatment of MDD all point toward major sex differences, the molecular mechanisms underlying this sexual dimorphism remain largely unknown. Here, combining differential expression and gene coexpression network analyses, we provide a comprehensive characterization of male and female transcriptional profiles associated with MDD across six brain regions. We overlap our human profiles with those from a mouse model, chronic variable stress, and capitalize on converging pathways to define molecular and physiological mechanisms underlying the expression of stress susceptibility in males and females. Our results show a major rearrangement of transcriptional patterns in MDD, with limited overlap between males and females, an effect seen in both depressed humans and stressed mice. We identify key regulators of sex-specific gene networks underlying MDD and confirm their sex-specific impact as mediators of stress susceptibility. For example, downregulation of the female-specific hub gene Dusp6 in mouse prefrontal cortex mimicked stress susceptibility in females, but not males, by increasing ERK signaling and pyramidal neuron excitability. Such Dusp6 downregulation also recapitulated the transcriptional remodeling that occurs in prefrontal cortex of depressed females. Together our findings reveal marked sexual dimorphism at the transcriptional level in MDD and highlight the importance of studying sex-specific treatments for this disorder.
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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.