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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.)

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

Sci. Rep. 11:21011 (2021)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: 21011 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Förderungen National Institute of Health
Fuqua Family Foundations
Office of Research Infrastructure Programs, National Institutes of Health