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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Depression

Intervention / Treatment
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* Biological: Biological analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psychiatry, Blood Brain Barrie, Suicide attempt, Inflammation