Inflammation and Blood Brain Barrier Integrity as Biomarkers of Suicidal Behavior
- Conditions
- DepressionSuicide
- Interventions
- Biological: Blood samplesOther: Hetero-questionnaires and auto-questionnairesOther: Magnetic Resonance Imaging (MRI)
- Registration Number
- NCT06047613
- 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 the blood brain barrier, which normally acts as a filter to ensure proper neuronal functioning, in suicidal patients.
They propose to investigate peripheral inflammation, neurovascular permeability and miRNAs in suicidal behavior pathophysiology as biomarkers of suicidal behavior in depression
- Detailed Description
150 participants will be enrolled, divided into 3 groups:
* 50 Suicide attempters, i.e. currently depressed patients with a suicide attempt within the 8 last days (with a maximal lifetime number of 3 previous suicide attempts, including the most recent);
* 50 Affective controls, i.e. currently depressed patients without any lifetime history of suicide attempt;
* 50 Healthy controls (age- and gender-matched to patients' groups) with no lifetime history of psychiatric disorders.
The protocol includes two visits for patients (suicide attempters and affective controls) and only one visit (inclusion) for healthy controls.
The first visit is the inclusion visit (Day 0-Day 8). Day 0 is the date of the last suicide attempt for the suicide attempters group and the date of signature of the consent for the affective control and healthy control groups. All the visit exams will be performed within 8 days after Day 0.
The second visit takes place one month +/- one week after inclusion. At each visit, a clinical assessment will be performed to characterise psychopathology and suicidal characteristics. Blood samples will be obtained in order to measure inflammatory markers. An MRI will be performed on order to study white matter microstructure and brain functional connectivity networks.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Healthy controls Blood samples Participants with no lifetime history of psychiatric disorders Healthy controls Magnetic Resonance Imaging (MRI) Participants with no lifetime history of psychiatric disorders Suicide attempters Hetero-questionnaires and auto-questionnaires Currently depressed patients with a suicide attempt within the 8 last days (with a maximal lifetime number of 3 previous suicide attempt including the most recent ); Suicide attempters Magnetic Resonance Imaging (MRI) Currently depressed patients with a suicide attempt within the 8 last days (with a maximal lifetime number of 3 previous suicide attempt including the most recent ); Affective controls Magnetic Resonance Imaging (MRI) Currently depressed patients without any lifetime history of suicide attempt Affective controls Blood samples Currently depressed patients without any lifetime history of suicide attempt Affective controls Hetero-questionnaires and auto-questionnaires Currently depressed patients without any lifetime history of suicide attempt Suicide attempters Blood samples Currently depressed patients with a suicide attempt within the 8 last days (with a maximal lifetime number of 3 previous suicide attempt including the most recent ); Healthy controls Hetero-questionnaires and auto-questionnaires Participants with no lifetime history of psychiatric disorders
- Primary Outcome Measures
Name Time Method Level of blood S100B assayed in the 3 groups, a marker of cerebral and vascular lesions. At 1 month follow-up
- Secondary Outcome Measures
Name Time Method FACS analysis on fresh blood At 1 month follow-up Percentage of cellular inflammatory marker
Extraction of small and long RNA At 1 month follow-up Use of RNA-seq, RT-qPCR and digital PCR to quantify RNA
Cytokines' concentration by multiplex ELISA (pg/ml) At 1 month follow-up C-C motif chemokine ligand (CCL)2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL20, CCL22, CCL26, C-X-C motif chemokine ligand (CXCL)10, Interleukin (IL)-1α, IL 1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23 p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL- 27, IL-31, interferon (IFN)-γ, Tumor Necrosis Factor ðTNFÞ α, TNF ß and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
White matter microstructure analysis At 1 month follow-up Value of fraction of perfusion fD\* ( incoherent blood signal divided by total incoherent signal) from different region based on regional atlases
Cerebral blood analysis At 1 month follow-up Extraction of blood flow values from 3D PCASL acquisition from vascular atlas
Specific proteins measurement (pg/ml) At 1 month follow-up Specific proteins measurement (i.e. GFAP, NFL, UHC-L1, sGPR56, S100B, MBP and related proteins) using digital or classical ELISA or western blot
Test of the capacity of leukocytes isolated from patients to provoke vascular inflammation and BBB permeabilization At 1 month follow-up These experiments will be performed using an in vitro model of vascular cell co-culture. The reactivity of leukocytes to pro-inflammatory challenges and cytokines will be tested.
Brain functional connectivity networks analysis : extraction of resting state functional connectivity metrics from functional atlas or by voxel At 1 month follow-up Graph theory metrics
Cerebral morphometric extraction (3DT1): automatic segmentation At 1 month follow-up Evaluation of the cortical thickness from cerebral anatomical atlas
Trial Locations
- Locations (1)
University hospital
🇫🇷Montpellier, France