TY - JOUR
T1 - Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia
AU - Severance, Emily G.
AU - Gressitt, Kristin L.
AU - Stallings, Cassie R.
AU - Origoni, Andrea E.
AU - Khushalani, Sunil
AU - Leweke, F. Markus
AU - Dickerson, Faith B.
AU - Yolken, Robert H.
N1 - Funding Information:
This work was supported by the Brain and Behavior Research Foundation (formerly NARSAD) where Dr. Severance is a Scott-Gentle Foundation Young Investigator; by a NIMH P50 Silvio O. Conte Center at Johns Hopkins (grant# MH-94268 ); and by the Stanley Medical Research Institute . These funding sources had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
PY - 2013/8
Y1 - 2013/8
N2 - 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 (R2=0.21, p<0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R2=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 (R2=0.27, p<0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R2=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.
AB - 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 (R2=0.21, p<0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R2=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 (R2=0.27, p<0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R2=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.
KW - Diet
KW - Gut
KW - Macrophage
KW - Mental illness
KW - Metabolic syndrome
KW - Microbiome
KW - Psychosis
UR - http://www.scopus.com/inward/record.url?scp=84881023923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881023923&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2013.05.018
DO - 10.1016/j.schres.2013.05.018
M3 - Article
C2 - 23746484
AN - SCOPUS:84881023923
SN - 0920-9964
VL - 148
SP - 130
EP - 137
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -