Chadi A Calarge1, Sridevi Devaraj2, Robert J Shulman3. 1. Menninger Department of Psychiatry and Behavioral Sciences and Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, 1102 Bates Ave, Suite 790 (C-0790.03) Houston, TX 77030, USA. Electronic address: chadi.calarge@bcm.edu. 2. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA. 3. Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
Abstract
OBJECTIVE: This study examined gut permeability in unmedicated adolescents with and without major depressive disorder. METHOD: 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 1β, interleukin 6, and tumor necrosis factor α) were measured. Correlational analyses were used to examine the associations between relevant variables. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: This study examined gut permeability in unmedicated adolescents with and without major depressive disorder. METHOD: 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 1β, interleukin 6, and tumor necrosis factor α) were measured. Correlational analyses were used to examine the associations between relevant variables. RESULTS: 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. CONCLUSIONS: 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.
Authors: Mark McOmber; Danny Rafati; Kevin Cain; Sridevi Devaraj; Erica M Weidler; Margaret Heitkemper; Robert J Shulman Journal: Clin Gastroenterol Hepatol Date: 2019-05-14 Impact factor: 11.382
Authors: Yara J Toenders; Liliana Laskaris; Christopher G Davey; Michael Berk; Yuri Milaneschi; Femke Lamers; Brenda W J H Penninx; Lianne Schmaal Journal: Mol Psychiatry Date: 2021-10-11 Impact factor: 15.992