Cited by 243Tryptophan and brain disordersSchizophrenia research and treatmentGut microbiota and health

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Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia

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Severance, Emily G., Gressitt, Kristin L., Stallings, Cassie R., Origoni, Andrea E., Khushalani, Sunil, Leweke, F. Markus, Dickerson, Faith B., Yolken, Robert H.·2013·Schizophrenia Research

DOI 10.1016/j.schres.2013.05.018PMC PMC3732507

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Abstract

The origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies. The two cohorts were composed of the following: (1) n=141 schizophrenia, n=75 bipolar disorder, n=78 controls; (2) n=78 antipsychotic-naïve first-episode schizophrenia, n=38 medicated first-episode schizophrenia. sCD14 seropositivity conferred a 3.1-fold increased odds of association with schizophrenia (multivariate regressions, OR=3.09, p<0.0001) compared to controls. Case-control differences in sCD14 were not matched by LBP. Quantitative levels of LBP, but not sCD14, correlated with BMI in schizophrenia (R(2)=0.21, p<0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R(2)=0.26-0.27, p<0.0001) and elevated in females compared to males (p<0.01). Antipsychotic treatment generally did not impact sCD14 or LBP levels except for significant correlations, especially sCD14, with gluten antibodies in antipsychotic-naïve schizophrenia (R(2)=0.27, p<0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R(2)=0.37, p<0.001). In conclusion, these bacterial translocation markers produced discordant and complex patterns of activity, a finding that may reflect an imbalanced, activated innate immune state. Whereas both markers may upregulate following systemic exposure to Gram-negative bacteria, non-lipopolysaccharide-based monocyte activation, autoimmunity and metabolic dysfunction may also contribute to the observed marker profiles.

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Authors: Severance, E. G., Gressitt, K. L., Stallings, C. R., Origoni, A. E., Khushalani, S., Leweke, F. M., Dickerson, F. B., & Yolken, R. H.
Affiliations: Johns Hopkins University (US)
Sheppard and Enoch Pratt Hospital (US)
University of Cologne (DE)
Corresponding author: Severance, Emily G.
ORCID: Severance, Emily G.
Stallings, Cassie R.
Origoni, Andrea E.
Khushalani, Sunil
Leweke, F. Markus
Dickerson, Faith B.
Yolken, Robert H.
Venue: Schizophrenia Research
Publisher: Elsevier BV
Published: 2013-08
Volume: 148
Issue: 1-3
Pages: 130-137
ISSN: 0920-9964 (ISSN-L)
DOI: 10.1016/j.schres.2013.05.018
PMC: PMC3732507
OpenAlex: W2106172174
Cited by: 243
References: 74
Citations by year: 2026: 7 · 2025: 16 · 2024: 18 · 2023: 22 · 2022: 13 · 2021: 23 · 2020: 23 · 2019: 23 · 2018: 22 · 2017: 17 · 2016: 24 · 2015: 19 · 2014: 13 · 2013: 3
FWCI: 6.65
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Schizophrenia Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (MH‑94268, P50MH094268)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (K08HD073315)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: bacterial translocation, soluble CD14
MeSH terms: Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Adult, Analysis of Variance, Autoantibodies, Bipolar Disorder, C-Reactive Protein, Carrier Proteins, Female, Humans, Male, Membrane Glycoproteins, Regression Analysis, Schizophrenia, Cohort Studies, Body Mass Index, Lipopolysaccharide Receptors

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Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia

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