RT Journal Article
SR Electronic
T1 Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.08.388942
DO 10.1101/2020.12.08.388942
A1 Christopher R Brydges
A1 Oliver Fiehn
A1 Helen S Mayberg
A1 Henry Schreiber
A1 Siamak Mahmoudian Dehkordi
A1 Sudeepa Bhattacharyya
A1 Jungho Cha
A1 Ki Sueng Choi
A1 W Edward Craighead
A1 Ranga R Krishnan
A1 A John Rush
A1 Boadie W Dunlop
A1 Rima Kaddurah-Daouk
A1 for the Mood Disorders Precision Medicine Consortium
YR 2020
UL http://biorxiv.org/content/early/2020/12/09/2020.12.08.388942.abstract
AB Background 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.Methods 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.Results 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, which suggests that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to gut microbiota.Conclusions 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.Competing Interest StatementDr. Dunlop has received research support from Acadia, Compass, Aptinyx, NIMH, Sage, and Takeda, and has served as a consultant to Greenwich Biosciences, Myriad Neuroscience, Otsuka, Sage, and Sophren Therapeutics. Dr. Rush has received consulting fees from Compass Inc., Curbstone Consultant LLC, Emmes Corp., Holmusk, Johnson and Johnson (Janssen), Liva-Nova, Neurocrine Biosciences Inc., Otsuka-US, Sunovion; speaking fees from Liva-Nova, Johnson and Johnson (Janssen); and royalties from Guilford Press and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named co-inventor on two patents: U.S. Patent No. 7,795,033: Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS; and U.S. Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S. Dr. Kaddurah-Daouk in an inventor on a series of patents on use of metabolomics for the diagnosis and treatment of CNS diseases and holds equity in Metabolon Inc.