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Research Project: Pediatric Clinical Nutrition

Location: Children's Nutrition Research Center

Title: Gut permeability and depressive symptom severity in unmedicated adolescents

item CALARGE, CHADI - Baylor College Of Medicine
item DEVARAJ, SRIDEVI - Baylor College Of Medicine
item SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Affective Disorders
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/24/2018
Publication Date: 3/1/2019
Citation: Calarge, C.A., Devaraj, S., Shulman, R.J. 2019. Gut permeability and depressive symptom severity in unmedicated adolescents. Journal of Affective Disorders. 246:586-594.

Interpretive Summary: Depression affects millions of people worldwide. Recent studies suggest that the gut may play a role in some people in worsening depression symptoms. The lining of the gut acts as a barrier to keep out harmful things that we eat in our diet or are produced by gut bacteria. In some individuals the gut barrier function is impaired. It is thought that dietary substances and/or bacterial products may leak across the gut barrier, get into the bloodstream, and then into the brain to contribute to depressive symptoms. This study examined the gut barrier function in adolescents with depression. We found that the worse the gut barrier function, the worse the depression. Future research is needed to identify dietary approaches to prevent this leakage to avoid potential cases of depression.

Technical Abstract: This study examined gut permeability in unmedicated adolescents with and without major depressive disorder. Medically healthy, non-medicated, 12-17 year-old females in a major depressive episode (MDE) or healthy controls, without any psychiatric condition, were enrolled. They completed the Children's Depression Rating Scale-Revised CDRS-R and underwent a clinical interview. Preejection period PEP and respiratory sinus arrhythmia RSA data were collected to measure autonomic nervous system activity. Following an overnight fast, participants ingested lactulose and mannitol and collected urine for 4 hours while still fasting, to examine gut permeability. Plasma cytokines interleukin 1B, interleukin 6, and tumor necrosis factor a were measured. Correlational analyses were used to examine the associations between relevant variables. 41 female participants age: 14.8+/-1.6 years, n+/-25 with MDE were enrolled. PEP, but not RSA, was inversely associated with neurovegetative symptom severity on the CDRS-R r+/-0.31, p<0.06. In the 30 participants with gut permeability data, the lactulose to mannitol ratio LMR was significantly positively associated with depression severity, particularly neurovegetative symptom severity r=0.37, p<0.05. Notably, the association between neurovegetative symptom severity and PEP was substantially reduced after adjusting for LMR. Additionally, depression severity was significantly associated with circulating cytokines. This is the first study to examine gut permeability in unmedicated adolescents, offering preliminary support for a mechanistic pathway linking sympathetic nervous system activation to increased gut permeability and activation of the innate immune system, likely contributing to the emergence of neurovegetative symptoms of depression.