Cited by 108Tryptophan and brain disordersTreatment of Major DepressionMetabolomics and Mass Spectrometry Studies

Metabolomic and inflammatory signatures of symptom dimensions in major depression

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Brydges, Christopher R., Bhattacharyya, Sudeepa, Dehkordi, Siamak Mahmoudian, Milaneschi, Yuri, Penninx, Brenda, Jansen, Rick, Kristal, Bruce S., Han, Xianlin +9 more·2022·Brain, Behavior, and Immunity

Published version of a preprint

Abstract

Background Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions.Methods Using three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism.Results The IMD clinical dimension and the inflammatory index were positively correlated (r = 0.19, p = 0.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids.Conclusion The IMD dimension of depression appears reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function.

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Crossref · 10.1016/j.bbi.2022.02.003

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Authors
Brydges, C. R., Bhattacharyya, S., Dehkordi, S. M., Milaneschi, Y., Penninx, B., Jansen, R., Kristal, B. S., Han, X., Arnold, M., Kastenmüller, G., Bekhbat, M., Mayberg, H. S., Craighead, W. E., Rush, A. J., Fiehn, O., Dunlop, B. W., & Kaddurah-Daouk, R.
Affiliations
  • University of California, Davis (US)
  • Arkansas State University (US)
  • Duke University (US)
  • GGZ inGeest (NL)
  • Amsterdam University Medical Centers (NL)
  • Amsterdam Neuroscience (NL)
  • Brigham and Women's Hospital (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • Helmholtz Munich (DE)
  • Emory University (US)
  • Texas Tech University (US)
Corresponding author
Kaddurah-Daouk, Rima
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2022-05
Volume
102
Pages
42-52
ISSN
0889-1591 (ISSN-L)
OpenAlex
W4225983076
Cited by
108
References
107
Citations by year
2026: 27 · 2025: 33 · 2024: 25 · 2023: 15 · 2022: 8
FWCI
7.04
Type
journal article
Language
en
Open access
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Site cant be reached (submittedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • National Institutes of Health (M01-RR0039, 5r01mh080880-05, RR0039, MH077083, RR025008, R01-MH080880, MH080880, RO1 MH080880)
  • National Institute on Aging (RF1AG059093, RF1AG058942, U19AG063744, U01AG061359, R01AG046171)
  • National Institute of Mental Health (R01MH108348, R01-MH080880, P50MH077083)
  • National Center for Research Resources (UL1RR025008, M01RR000039)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
major depressive disorder, symptom dimensions, inflammation, metabolomics, endogenous depression, anxious distress, NESDA, interleukin-6, C-reactive protein, gut microbiota metabolites, free fatty acids, phosphatidylcholine, sphingomyelin, bile acids, amino acids, acylcarnitines, depression heterogeneity
MeSH terms
Amino Acids, Depression, Major Depressive Disorder, Fatty Acids, Nonesterified, Humans, Metabolomics

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