ArticleThe Journal of clinical investigation2020
The glucocorticoid receptor-FKBP51 complex contributes to fear conditioning and posttraumatic stress disorder.
Article in The Journal of clinical investigation, 2020. 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.
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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Causal relationships between hundreds of plasma metabolites and PTSD: a bidirectional mendelian randomization study.BMC psychiatry · 2025Pooled it
- A novel composite model of PTSD induced by social bullying: validation via multidimensional behavioral and molecular biomarkers.Molecular psychiatry · 2026Article
- Chronic Pre-Trauma Corticosterone Attenuates Trauma Memory Formation and Alters Gene Expression in Glucocorticoid Signalling Pathways.Genes, brain, and behavior · 2026Article
- From Biomarkers to New Treatments for Post-Traumatic Stress Disorder.Neuroscience bulletin · 2026Review
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Investigational drugs in PTSD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- Unraveling Complex Interactions Mechanisms Linking PTSD and Chronic Diseases.Current neuropharmacology · 2026Review
- Standardized rice bran supplement ameliorates depressive behaviors via FKBP5 mediated glucocorticoid receptor signaling.NPJ science of food · 2025Article
- PET imaging evidence of HDAC6 suppression in the amygdala across species in PTSD.Molecular psychiatry · 2025Article
- Stress-induced changes in the molecular processes underlying fear memories: implications for PTSD and relevant animal models.Molecular psychiatry · 2025Review
- Article
- Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice.Cells · 2024Article
- Reducing FKBP51 Expression in the Ventral Hippocampus Decreases Auditory Fear Conditioning in Male Rats.International journal of molecular sciences · 2024Article
- The Role of FKBPs in Complex Disorders: Neuropsychiatric Diseases, Cancer, and Type 2 Diabetes Mellitus.Cells · 2024Review
- EF1α-associated protein complexes affect dendritic spine plasticity by regulating microglial phagocytosis in Fmr1 knock-out mice.Molecular psychiatry · 2024Article
- Chronic adolescent stress alters GR-FKBP5 interactions in the hippocampus of adult female rats.Stress (Amsterdam, Netherlands) · 2024Article
- Cytotoxic CD4Med (New York, N.Y.) · 2023Article
- SIRT1 in the BNST modulates chronic stress-induced anxiety of male mice via FKBP5 and corticotropin-releasing factor signaling.Molecular psychiatry · 2023Article
- Time-course analysis of frontal gene expression profiles in the rat model of posttraumatic stress disorder and a comparison with the conditioned fear model.Neurobiology of stress · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Posttraumatic stress disorder (PTSD) can develop after exposure to severe psychological trauma, leaving patients with disabling anxiety, nightmares, and flashbacks. Current treatments are only partially effective, and development of better treatments is hampered by limited knowledge of molecular mechanisms underlying PTSD. We have discovered that the glucocorticoid receptor (GR) and FK506 binding protein 51 (FKBP51) form a protein complex that is elevated in PTSD patients compared with unaffected control subjects, subjects exposed to trauma without PTSD, and patients with major depressive disorder (MDD). The GR-FKBP51 complex is also elevated in fear-conditioned mice, an aversive learning paradigm that models some aspects of PTSD. Both PTSD patients and fear-conditioned mice had decreased GR phosphorylation, decreased nuclear GR, and lower expression of 14-3-3ε, a gene regulated by GR. We created a peptide that disrupts GR-FKBP51 binding and reverses behavioral and molecular changes induced by fear conditioning. This peptide reduces freezing time and increases GR phosphorylation, GR-FKBP52 binding, GR nuclear translocation, and 14-3-3ε expression in fear-conditioned mice. These experiments demonstrate a molecular mechanism contributing to PTSD and suggest that the GR-FKBP51 complex may be a diagnostic biomarker and a potential therapeutic target for preventing or treating PTSD.
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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.