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

Not Applicable

• Conditions: Depression
• Interventions: Biological: Biological analysis

• Registration Number: NCT04137458
• Lead Sponsor: University Hospital, Montpellier

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-10-21
• Study First Submitted QC: 2019-10-21
• Study First Posted: 2019-10-24
• Study Start: 2019-11-07
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-22
• Last Update Posted: 2021-10-25
• Primary Completion: 2022-07
• Study Completion: 2022-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 105

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants	Biological analysis	The investigator will withdraw biological samples and a biological and DNA bank will also be realized

Primary Outcome Measures

Name	Time	Method
Blood level of S100B	at inclusion	Blood level of S100B measured in 3 groups (i.e. suicide attempters, affective controls, healthy controls)

Secondary Outcome Measures

Name	Time	Method
Salivary levels of GFAP	at inclusion	Between group comparison of salivary levels of GFAP in the 3 groups
Identification of general peripheral inflammation	at inclusion	Between groups comparison of blood levels of CRP
Determination of leukocyte signature associated with suicidal behavior and depression	at inclusion	Comparison of the number and percentage of leukocytes (lymphocytes, monocytes, neutrophils) in the blood between the 3 patients groups
Profile of salivary interleukins	at inclusion	Profile of salivary interleukins Il-6, Il-13 et Il-17 within and between groups
Serum levels of glial fibrillary actin protein (GFAP)	at inclusion	Between group comparison of serum levels (ng / ml) of glial fibrillary actin protein (GFAP)
Serum levels of ubiquitinar-carboxy-terminal hydrolase L1 (UCH-L1)	at inclusion	Between group comparison of serum levels (ng / ml) of ubiquitinar-carboxy-terminal hydrolase L1 (UCH-L1)
Profile of peripheral inflammation of each group	at inclusion	Characterization of activation state of leukocytes of CD4 / CD8 (T cells), NK cells, CD14 / CD33 (monocytes / macrophages)
Pro-inflammatory profile based on cytokins of each group	at inclusion	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
Serum levels of specific neuronal enolase (NSE)	at inclusion	Between group comparison of serum levels (ng / ml) of specific neuronal enolase (NSE)
Salivary levels of S100B protein	at inclusion	Between group comparison of salivary levels of S100B protein
Salivary levels of specific neuronal enolase (NSE)	at inclusion	Between group comparison of salivary levels of specific neuronal enolase (NSE) in the 3 groups
In vitro fluorescence ratio Dapi / phalloidin	at inclusion	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

Trial Locations

Locations (1)

University hospital; 🇫🇷 Montpellier, France