Clinical trial NCT06203015: The Relations Among Endotoxin, Inflammatory Cytokines, Cognitive Markers and Brain MRI Changes in Subjects With Depressive Disorder
Official title: The Relations Among Endotoxin, Inflammatory Cytokines, Cognitive Markers and Brain MRI Changes in Subjects With Depressive Disorder
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Major Depressive Disorder
Inflammation
Cognitive Dysfunction
Endotoxemia
Genetic Predisposition to Disease
Blood Brain Barrier Defect
Keywords: Major depressive disorder
Inflammation
Endotoxin
Cognitive dysfunction
Genetic polymorphisms
Multiparametric Magnetic Resonance Imaging
Blood Brain Barrier
Lead sponsor: Lithuanian University of Health Sciences
Sponsor class: OTHER
First posted: 2024-01-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: The study is being conducted at the hospital of the Lithuanian University of Health Sciences Kaunas Clinics Psychiatry Clinic (inpatient department), and the Nervous System Diseases Outpatient Department.

Brief summary: Major depressive disorder (MDD) is a chronic mental illness, with 60% lifetime risk of recurrence after the first MDD episode. Despite available treatment options for MDD, only about half to two-thirds of patients respond to first-line antidepressant treatment, and only 30% to 45% of patients achieve remission. Scholars assume that this low remission rate and high rate of treatment resistance are due to the polyetiological nature of the disease, the heterogeneity of the clinical picture of depression, and the lack of biomarkers to stratify MDD subtypes. The aetiology of MDD, although researched extensively, remains unclear. None of the known mechanisms alone explains the pathogenesis of depression, meaning that the interplay of several factors contributes to the development of MDD. Accumulated scientific evidence has supported the importance of the immune system in the etiopathogenesis of MDD. Until now, the cause of the low-grade inflammation observed in this subgroup of MDD patients has been unclear. In the proposed study, the investigators will test a new hypothesis of the immune theory of the development of MDD: the endotoxin hypothesis of neurodegeneration. This hypothesis states that endotoxin, causes or contributes to neurodegeneration. Blood plasma levels of LPS are normally low but are elevated during infections, gut inflammation, gum disease, and neurodegenerative diseases. Dysbiosis may promote increased intestinal permeability ("leaky gut"), which leads to bacterial translocation across the intestinal barrier and into the circulation, thus forming of LPS and LPS-binding protein complex, which triggers the secretion of cytokines. Data suggest that LPS-induced peripheral inflammation can activate neuroinflammation. However, it is not known whether a low-level persistent presence of LPS in the circulatory system can cause low-grade chronic neuroinflammation leading to neurodegeneration and/or symptoms of MDD. Based on existing preclinical and clinical research data, the investigators hypothesise that an increase in blood plasma endotoxin and peripheral cytokines induce BBB dysfunction, neuroinflammation and neurodegenerative processes in specific etiologically relevant structures of the brain and cause clinical manifestation of depressive symptoms and cognitive damage. In this study the investigators are also going to investigate the effects of single nucleotide polymorphisms of four genes in relation to blood plasma endotoxin and peripheral cytokines concentrations and clinical manifestation of MDD.


Eligibility criteria: Inclusion Criteria:

* ≥18 years old
* signed informed consent
* patients diagnosed with MDD (according to the WHO's \[2019\] International Classification of Diseases and related health problems categorization of mental disorders) for MDD group.

Exclusion Criteria:

* diagnosis of other mental disorders during the past one-year period (for MDD group).
* diagnosis of any mental disorders within the past one-year period, previous suicide attempt, or current suicide risk identified in the study (for control group).
* diagnosis of somatic diseases that may affect changes in inflammatory factors in the body (for both groups)

Primary outcomes:
measure: Levels of blood plasma endotoxin and inflammatory cytokines between groups.
timeFrame: Day 1
measure: Severity and manifestation of depressive symptoms.
timeFrame: Day 1
Secondary outcomes:
measure: Brain MRI
timeFrame: Day 1
measure: Cognitive dysfunction
timeFrame: Day 1
measure: Covariates
timeFrame: Day 1
measure: Genetic markers
timeFrame: Day 1
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Psychiatry Department, Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Kaunas
country: Lithuania
facility: Psychiatry Department, Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Study officials:
affiliation: Proffesor, Lithuanian University of Health Sciences
name: Vesta Steibliene, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: