Exploration of the Relationship Between Inflammation and Integrity of the Blood-Brain Barrier in Suicidal Behaviour (IBIS)

Exploration of the the Relationship Between Inflammation and Integrity of the Blood-brain Barrier in Suicidal Behaviour

Recent studies have revealed an association between history of suicide attempt and inflammatory markers in both the cerebrospinal fluid and the plasma. Post mortem studies have shown an increase in microglial activation in the brain tissue of suicide victims. However the relationship between peripheral and central inflammation in suicide is probably mediated by complex biological processes that are yet elucidated. An increase of blood S100B levels (biomarker of neurovascular damage; PMID 14530574) has been reported in adolescents with suicidal ideation vs. controls and independently of psychiatric disorder. The investigators hypothesize that peripheral inflammation may alter BBB which normally acts as a filter to ensure proper neuronal functioning in suicidal vs. non suicidal patients.

Study Overview

• Status: Recruiting
• Conditions: Depression
• Intervention / Treatment: Biological: Biological analysis

Detailed Description

105 participants will be recruited :

• 35 depressed patients having attempted suicide (maximum 3 attempts in life)
• 35 depressed patients without history of suicide attempt (affective controls)
• 35 healhy controls with no lifetime psychiatric history.

Only one visit is planned. A clinical assessment (2 hours) will be performed to characterise pschopathology and suicidal characteristics. Blood and salivary samples will be obtained in order to measure inflammatory markers.

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philippe COURTET, MD PhD; Phone Number: +33 4 67 33 85 81; Email: p-courtet@chu-montpellier.fr
• Study Contact Backup: Name: Emilie OLIE, MD PhD; Phone Number: +33 4 67 33 85 81; Email: e-olie@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • University Hospital
    • Contact: Catherine GENTY, MD; Phone Number: +33 4 67 99 61 45 75; Email: c-genty@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-55 years old
• Able to understand nature, aims, and methodology of the study

Depending on the population :

• Current depressive episode (according to DSM-5 criteria) with a recent suicide attempt (within the 8 days before inclusion) and no more than 3 attempts in life
• Current depressive episode (according to DSM-5 criteria) without suicide attempt
• No psychiatric history (according to DSM-5 criteria)

Exclusion Criteria:

• Inflammatory diseases or intercurrent infections, or chronic diseases such as hepatitis C or B, HIV, Alzheimer's, cancer or autoimmune disease
• Current antibiotic or anti-inflammatory treatments
• Refusal to participate
• Lifetime Schizoaffective disorder or schizophrenia
• On protective measures (guardianship or trusteeship)
• Deprived of liberty subject (administrative decision)
• In exclusion period for another protocol
• Not affiliated to a social security agency
• Unable to understand and/or answer a questionnaire
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants; The investigator will withdraw biological samples and a biological and DNA bank will also be realized	Biological: Biological analysis; Blood and salivary samples will be taken at inclusion and a psychiatric assessment will be carried out

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood level of S100B	Blood level of S100B measured in 3 groups (i.e. suicide attempters, affective controls, healthy controls)	at inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of leukocyte signature associated with suicidal behavior and depression	Comparison of the number and percentage of leukocytes (lymphocytes, monocytes, neutrophils) in the blood between the 3 patients groups	at inclusion
Profile of peripheral inflammation of each group	Characterization of activation state of leukocytes of CD4 / CD8 (T cells), NK cells, CD14 / CD33 (monocytes / macrophages)	at inclusion
Identification of general peripheral inflammation	Between groups comparison of blood levels of CRP	at inclusion
Pro-inflammatory profile based on cytokins of each group	Serum pro-inflammatory interleukins (IL) -1b, IL2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13 , TGF-b, interferon IFN-g, TNF-a, TNF-b	at inclusion
Profile of salivary interleukins	Profile of salivary interleukins Il-6, Il-13 et Il-17 within and between groups	at inclusion
Serum levels of glial fibrillary actin protein (GFAP)	Between group comparison of serum levels (ng / ml) of glial fibrillary actin protein (GFAP)	at inclusion
Serum levels of specific neuronal enolase (NSE)	Between group comparison of serum levels (ng / ml) of specific neuronal enolase (NSE)	at inclusion
Serum levels of ubiquitinar-carboxy-terminal hydrolase L1 (UCH-L1)	Between group comparison of serum levels (ng / ml) of ubiquitinar-carboxy-terminal hydrolase L1 (UCH-L1)	at inclusion
Salivary levels of S100B protein	Between group comparison of salivary levels of S100B protein	at inclusion
Salivary levels of specific neuronal enolase (NSE)	Between group comparison of salivary levels of specific neuronal enolase (NSE) in the 3 groups	at inclusion
Salivary levels of GFAP	Between group comparison of salivary levels of GFAP in the 3 groups	at inclusion
In vitro fluorescence ratio Dapi / phalloidin	The fluorescence ratio Dapi / phalloidin in a culture of neurovascular cells in the presence of the serum of the subjects (in vitro) in the 3 groups	at inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Philippe Courtet, MD PhD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2019
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 24, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Inflammation; Psychiatry; Suicide attempt; Blood Brain Barrie
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: RECHMPL19_0227; 2019-A01277-50 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No