ArticleThe international journal of neuropsychopharmacology2014
Hypothalamic-pituitary-adrenal axis dysfunction and illness progression in bipolar disorder.
Erratum issuedOpen access · hybridAbstract read
In one paragraph
Article in The international journal of neuropsychopharmacology, 2014. 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 42 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
12.2field-weighted citation impact, top 1% of its field
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
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Biomarkers of neuroprogression and late staging in bipolar disorder: A systematic review.The Australian and New Zealand journal of psychiatry · 2023Pooled it
- Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development.EBioMedicine · 2017Pooled it
- Elevated heat shock proteins in bipolar disorder patients with hypothalamic pituitary adrenal axis dysfunction.Medicine · 2018Trial
- Allostatic and Circadian Drives in Patients with Bipolar Disorder in Depressive Episodes or with Post-Traumatic Stress Disorder Versus Healthy Controls: Neuroendocrine Comparison Through Cortisol and 6-Sulfatoxymelatonin Overnight Urine Excretion.International journal of molecular sciences · 2026Article
- Functional Genomics Studies of Psychiatric Disorders in Individuals of Latin American Populations: A Scoping Review.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2026Article
- Associations of TNF-α, MIF, and cortisol with cognitive function in patients with bipolar disorder during acute manic episodes: a short-term follow-up study.Frontiers in psychiatry · 2026Article
- The kynurenine pathway in depression and schizophrenia: convergent signals, divergent states, and clinical signatures.EXCLI journal · 2026Review
- Reconceptualizing bipolar disorder through an integrative biological lens: synthesis, convergence, and emerging directions.Frontiers in integrative neuroscience · 2026Review
- The Role of the Gut Microbiome Dysbiosis in Metabolic Dysfunction: A Mini Review.Healthcare (Basel, Switzerland) · 2025Review
- Epigenetics, Resilience, Protective Factors and Factors Promoting Positive Outcomes: A Scoping Review.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2025Article
- Ferroptosis as a potential molecular mechanism of bipolar disorder.Translational psychiatry · 2025Review
- Immune-neuroendocrine crosstalk in mood and psychotic disorders: A meta-analysis and systematic review.Brain, behavior, & immunity - health · 2025Review
- SKA2 enhances stress-related glucocorticoid receptor signaling through FKBP4-FKBP5 interactions in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Neural functional connectivity changes to psychosocial stress in young adults with bipolar disorder and preliminary associations with clinical trajectories.Bipolar disorders · 2022Article
- Sleep disturbances in the context of neurohormonal dysregulation in patients with bipolar disorder.International journal of bipolar disorders · 2022Article
- Chronic Stress in Bipolar Disorders Across the Different Clinical States: Roles of HPA Axis and Personality.Neuropsychiatric disease and treatment · 2022Article
- Associations between the cortisol awakening response and patient-evaluated stress and mood instability in patients with bipolar disorder: an exploratory study.International journal of bipolar disorders · 2021Article
- Circadian Rhythms of the Hypothalamus: From Function to Physiology.Clocks & sleep · 2021Review
- The Greater Houston Area Bipolar Registry-Clinical and Neurobiological Trajectories of Children and Adolescents With Bipolar Disorders and High-Risk Unaffected Offspring.Frontiers in psychiatry · 2021Article
- Pre- and Post-treatment Levels of Plasma Metabolites in Patients With Bipolar Depression.Frontiers in psychiatry · 2021Article
Corrections and comments
- Erratum issuedErratum.2016
Authors and funding
13 authors at 3 institutions in 2 countries.
Gabriel Rodrigo FriesINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg). gabrielrfries@gmail.com.
Mirela Paiva Vasconcelos-MorenoINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Carolina GubertINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Bárbara Tietböhl Martins Quadros dos SantosINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Juliana SartoriINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Bárbara EiseleINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Pamela FerrariINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Adam FijtmanINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Joëlle RüeggINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Nils Christian GassenINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Flávio KapczinskiINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Theo ReinINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Márcia Kauer-Sant'AnnaINCT for Translational Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (Drs Fries, Vasconcelos-Moreno, Gubert, dos Santos, Sartori, Eisele, Ferrari, Fijtman, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, Brazil (Drs Fries, Gubert, Kapczinski, and Kauer-Sant'Anna); Programa de Pós-Graduação em Ciências Médicas: Psiquiatria, UFRGS, Porto Alegre, Brazil (Drs Vasconcelos-Moreno, Ferrari, Kapczinski, and Kauer-Sant'Anna); Max Planck Institute of Psychiatry, Munich, Germany (Drs Gassen and Rein); Karolinska Institute, Stockholm, Sweden (Dr Rüegg).
Universidade Federal do Rio Grande do Sul · BRHospital de Clínicas de Porto Alegre · BRMax Planck Institute of Psychiatry · DE
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImpaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients.
methodsTwenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR).
resultsPatients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels.
conclusionsOur data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness.
Indexed as
Adrenocorticotropic HormoneAdultBipolar DisorderDexamethasoneDisease ProgressionEpigenesis, GeneticFemaleGlucocorticoidsHumansHydrocortisoneHypothalamo-Hypophyseal SystemLeukocytes, MononuclearMaleMethylationMiddle AgedPituitary-Adrenal SystemAdrenocorticotropic HormoneDexamethasoneGlucocorticoidsHydrocortisoneReceptors, GlucocorticoidRNA, MessengerTacrolimus Binding Protein 5Tacrolimus Binding Proteinsbipolar disordercortisolFKBP51glucocorticoid receptorHPA axis.
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