Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature

Autor: Brydges, C.R., Fiehn, O., Mayberg, H.S., Schreiber, H., Dehkordi, S.M., Bhattacharyya, S., Cha, J., Choi, K.S., Craighead, W.E., Krishnan, R.R., Rush, A.J., Dunlop, B.W., Kaddurah-Daouk, R., Mood Disorders Precision Medicine Consortium (Kastenmüller, G.), Mood Disorders Precision Medicine Consortium (Arnold, M.)
Přispěvatelé: Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Cingulate cortex
medicine.medical_treatment
Anxiety
Bioinformatics
chemistry.chemical_compound
Medicine
Uremic Toxins
Multidisciplinary
Depression
Brain
Middle Aged
Anxiety Disorders
Magnetic Resonance Imaging
Cognitive behavioral therapy
Mental Health
Metabolome
Antidepressant
Major depressive disorder
Female
Disease Susceptibility
Symptom Assessment
medicine.symptom
Metabolic Networks and Pathways
medicine.drug
Adult
medicine.medical_specialty
Science
Article
Young Adult
Clinical Research
Internal medicine
Complementary and Integrative Health
Behavioral and Social Science
Metabolomics
Humans
Duloxetine
Escitalopram
Aged
Mood Disorders Precision Medicine Consortium
Resting state fMRI
business.industry
Functional Neuroimaging
Neurosciences
medicine.disease
Gastrointestinal Microbiome
Endocrinology
chemistry
business
Indican
Biomarkers
Neuroscience
Zdroj: the Mood Disorders Precision Medicine Consortium 2021, ' Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature ', Scientific Reports, vol. 11, no. 1, 21011 . https://doi.org/10.1038/s41598-021-99845-1
Sci. Rep. 11:21011 (2021)
Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
Scientific Reports, 11(1):21011. Nature Publishing Group
Scientific Reports
Scientific reports, vol 11, iss 1
ISSN: 2045-2322
DOI: 10.1038/s41598-021-99845-1
Popis: It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). The relation between indoxyl sulfate and psychic anxiety was mediated only through the metabolite’s effect on the SCC-FC with the premotor area. Baseline indole abundances were unrelated to post-treatment outcome measures, and changes in symptoms were not correlated with changes in indole concentrations. These results suggest that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to modulation of indoles derived from gut microbiota; it remains possible that treatment-related improvement stems from their impact on other aspects of the gut microbiome. A peripheral gut microbiome-derived metabolite was associated with altered neural processing and with psychiatric symptom (anxiety) in humans, which provides further evidence that gut microbiome disruption can contribute to neuropsychiatric disorders that may require different therapeutic approaches. Given the exploratory nature of this study, findings should be replicated in confirmatory studies.Clinical trial NCT00360399 “Predictors of Antidepressant Treatment Response: The Emory CIDAR” https://clinicaltrials.gov/ct2/show/NCT00360399.
Databáze: OpenAIRE
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