ArticleAmerican journal of physiology. Endocrinology and metabolism2019
Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity.
Article in American journal of physiology. Endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.Psychopharmacology · 2025Pooled it
- Prelimbic cortex-associated stress sensitisation and region-specific mitochondrial adaptations across preclinical approaches relevant to PTSD and depression.Neurobiology of stress · 2026Article
- Towards scalable biomarker discovery in posttraumatic stress disorder: triangulating genomic and phenotypic evidence from a health system biobank.Molecular psychiatry · 2026Article
- Sex-dependent neurobiological and metabolic dysfunction in an aged rat model of post-traumatic stress disorder.Communications biology · 2026Article
- Cortical morphological changes and associated transcriptional signatures in post-traumatic stress disorder and psychological resilience.BMC medicine · 2024Article
- Identifying genetic loci that are associated with changes in gene expression in PTSD in a South African cohort.Journal of neurochemistry · 2023Article
- 360-Degree Perspectives on Obesity.Medicina (Kaunas, Lithuania) · 2023Review
- Molecular signatures of post-traumatic stress disorder in war-zone-exposed veteran and active-duty soldiers.Cell reports. Medicine · 2023Article
- Molecular Toxicology and Pathophysiology of Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder Associated with Traumatic Brain Injury.International journal of molecular sciences · 2023Review
- Overnight Corticosterone and Gene Expression in Mouse Hippocampus: Time Course during Resting Period.International journal of molecular sciences · 2023Article
- Risk Factors and Mechanisms of Cardiovascular Diseases in Posttraumatic Stress Disorder Model in Wistar Rats as Dependent on Stress Resistance and Age.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2022Article
- Inflammation-driven brain and gut barrier dysfunction in stress and mood disorders.The European journal of neuroscience · 2022Review
- Chemical set enrichment analysis: Novel insights into sex-specific alterations in primary metabolites in posttraumatic stress and disturbed sleep.Clinical and translational medicine · 2021Article
- Cross-Platform Evaluation of Commercially Targeted and Untargeted Metabolomics Approaches to Optimize the Investigation of Psychiatric Disease.Metabolites · 2021Article
- Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders.Metabolites · 2021Article
- [A Review of Research Progress in the Pathophysiological Mechanism of Stress-related Mental Disorders].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Review
- Diazepam ameliorates altered proinflammatory and cardiac markers in stress exposed rats.Saudi journal of biological sciences · 2021Article
- Neurophysiology and Psychopathology Underlying PTSD and Recent Insights into the PTSD Therapies-A Comprehensive Review.Journal of clinical medicine · 2020Review
- Novel Pharmacological Targets for Combat PTSD-Metabolism, Inflammation, The Gut Microbiome, and Mitochondrial Dysfunction.Military medicine · 2020Article
- Translating Molecular and Neuroendocrine Findings in Posttraumatic Stress Disorder and Resilience to Novel Therapies.Biological psychiatry · 2019Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Posttraumatic stress disorder (PTSD) is associated with neuroendocrine alterations and metabolic abnormalities; however, how metabolism is affected by neuroendocrine disturbances is unclear. The data from combat-exposed veterans with PTSD show increased glycolysis to lactate flux, reduced TCA cycle flux, impaired amino acid and lipid metabolism, insulin resistance, inflammation, and hypersensitive hypothalamic-pituitary-adrenal (HPA) axis. To analyze whether the co-occurrence of multiple metabolic abnormalities is independent or arises from an underlying regulatory defect, we employed a systems biological approach using an integrated mathematical model and multiomic analysis. The models for hepatic metabolism, HPA axis, inflammation, and regulatory signaling were integrated to perform metabolic control analysis (MCA) with respect to the observations from our clinical data. We combined the metabolomics, neuroendocrine, clinical laboratory, and cytokine data from combat-exposed veterans with and without PTSD to characterize the differences in regulatory effects. MCA revealed mechanistic association of the HPA axis and inflammation with metabolic dysfunction consistent with PTSD. This was supported by the data using correlational and causal analysis that revealed significant associations between cortisol suppression, high-sensitivity C-reactive protein, homeostatic model assessment of insulin resistance, γ-glutamyltransferase, hypoxanthine, and several metabolites. Causal mediation analysis indicates that the effects of enhanced glucocorticoid receptor sensitivity (GRS) on glycolytic pathway, gluconeogenic and branched-chain amino acids, triglycerides, and hepatic function are jointly mediated by inflammation, insulin resistance, oxidative stress, and energy deficit. Our analysis suggests that the interventions to normalize GRS and inflammation may help to manage features of metabolic dysfunction in PTSD.
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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.