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The intestinal microbiota as a predictor for antidepressant treatment outcome in geriatric depression: a prospective pilot study

Published online by Cambridge University Press:  24 March 2021

S. Melanie Lee ,
Tien S. Dong ,
Beatrix Krause-Sorio Open the ORCID record for Beatrix Krause-Sorio [Opens in a new window] ,
Prabha Siddarth ,
Michaela M. Milillo Open the ORCID record for Michaela M. Milillo [Opens in a new window] ,
Venu Lagishetty ,
Tanya Datta ,
Yesenia Aguilar-Faustino ,
Jonathan P. Jacobs  and
Helen Lavretsky
S. Melanie Lee
Affiliation:
Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA
Tien S. Dong
Affiliation:
The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA UCLA Microbiome Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Beatrix Krause-Sorio
Affiliation:
Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA
Prabha Siddarth
Affiliation:
Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA
Michaela M. Milillo
Affiliation:
Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA
Venu Lagishetty
Affiliation:
The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA UCLA Microbiome Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Tanya Datta
Affiliation:
Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA
Yesenia Aguilar-Faustino
Affiliation:
Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA
Jonathan P. Jacobs
Affiliation:
The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA UCLA Microbiome Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System and Department of Medicine and Human Genetics, Los Angeles, CA, USA
Helen Lavretsky*
Affiliation:
Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA
*
Correspondence should be addressed to: Helen Lavretsky, Professor of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 760 Westwood Plaza, 37-456, Los Angeles, CA, 90095, USA. Phone: 310-794-4619. Email: [email protected].
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Abstract

Objectives:

(1) To investigate if gut microbiota can be a predictor of remission in geriatric depression and to identify features of the gut microbiota that is associated with remission. (2) To determine if changes in gut microbiota occur with remission in geriatric depression.

Design:

Secondary analysis of a parent randomized placebo-controlled trial (NCT02466958).

Setting:

Los Angeles, CA, USA (2016-2018)

Participants:

Seventeen subjects with major depressive disorder, over 60 years of age, 41.2% female.

Intervention:

Levomilacipran (LVM) or placebo.

Measurements:

Remission was defined by Hamilton Depression Rating Scale score of 6 or less at 12 weeks. 16S-ribosomal RNA sequencing based fecal microbiota composition and diversity were measured at baseline and 12 weeks. Differences in fecal microbiota were evaluated between remitters and non-remitters as well as between baseline and post-treatment samples. LVM and placebo groups were combined in all the analyses.

Results:

Baseline microbiota showed no community level α-diversity or β-diversity differences between remitters and non-remitters. At the individual taxa level, a random forest classifier created with nine genera from the baseline microbiota was highly accurate in predicting remission (AUC = .857). Of these, baseline enrichment of Faecalibacterium, Agathobacter and Roseburia relative to a reference frame was associated with treatment outcome of remission. Differential abundance analysis revealed significant genus level changes from baseline to post-treatment in remitters, but not in non-remitters.

Conclusions:

This is the first study demonstrating fecal microbiota as a potential predictor of treatment response in geriatric depression. Our findings need to be confirmed in larger prospective studies.

Keywords

antidepressantgut microbiotageriatric depressionMDDpredictor of treatment responseprecision medicinelevomilnacipran
Type
Original Research Article
Information
International Psychogeriatrics , Volume 34 , Special Issue 1: Issue Theme: Varied Angles of Geriatric Depression , January 2022 , pp. 33 - 45
Copyright
© International Psychogeriatric Association 2021

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