Inflammatory Biomarkers and Brain Metabolites, a Study Based on Magnetic Resonance Spectroscopy

Study Overview
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Brief Summary
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Suicidal behaviors (SB) are a major health problem in France : 10 000 suicides and 220 000 suicide attempts every year. SB management is therefore a major public health issue. Evidence associated dysregulation of the serotonergic system and the hypothalamic-pituitary-adrenal axis to vulnerability to SB. Recent data point to linke these abnormalities with neuroinflammatory clues, glutamatergic function and neuronal plasticity. There is a need to better understand the physiopathology and develop diagnostic and therapeutic tools in SB. The investigators hypothesize that increased peripheral biomarkers of inflammation would correlate to a disturbance of the cerebral metabolites, such as glutamate and NAA, especially in suicidal patients. Our aim is to compare rates of cerebral metabolites, in particular the complex glutamine/glutamate, in cerebral areas involved in suicidal vulnerability (the anterior cingulate cortex and the orbito-frontal cortex) between person with unipolar disorder with and without suicidal attempt.

Detailed Description
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69 patients : 23 with suicidal thoughts and attempt, 23 with suicidal thoughts without attempt and 23 healthy volunteers. 2 visits : Inclusion visit (V0) : (Day 1) o Clinical interview : self and hetero assessment questionnaire Visit V1 (as soon as possible, day 1 if available) : MRI (spectroscopy)

Official Title
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Title: Inflammatory Biomarkers and Brain Metabolites, a Study Based on Magnetic Resonance Spectroscopy.

Conditions
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Depression

Intervention / Treatment
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* Other: Magnetic Resonance Imaging (MRI) and biological samples


Participation Criteria
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Eligibility Criteria
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Non-specific inclusion criteria: Having signed informed consent Able to understand nature, aims and methodology of the study Specific inclusion criteria : Suicidal patient with suicide attempt : Persistent depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders - V (DSM-V) criteria, and evaluated by the Mini International Neuropsychiatric Interview (MINI) Hamilton Depression Scale > 7 Suicide attempt < 1 week Suicidal patient without suicide attempt : Persistent depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders - V (DSM-V) criteria, and evaluated by the Mini International Neuropsychiatric Interview (MINI) Hamilton Depression Scale > 7 No history of suicide attempt Healthy volunteers : No psychiatric history No history of suicide attempt Exclusion criteria: Actual somatic, neurological or inflammatory pathology (C-Reactive Protein > 10mg/L) Traumatic brain injury with loss of consciousness Antibiotic treatment or anti-inflammatory treatment Actual toxic abuse according to DSM-V (except tobacco and alcohol) Actual or passed history of psychotic disorder Patient on protective measures (guardianship or trusteeship) Deprived of liberty subject (judicial or administrative decision) Pregnant women or breastfeeding Contraindications to MRI scan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Other: Participants<br>All the participants of the 3 groups (depressed patients with suicide attempt, depressed patients without suicide attempt, healthy volunteers) will have to realize a MRI and biological samples. | Other: Magnetic Resonance Imaging (MRI) and biological samples<br>* Participants will have to do a MRI and biological samples.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glutamine (Glu) and Glutamate (Glx) levels | Levels of Glu/Glx in the anterior cingulate cortex and the orbitofrontal cortex between the depressed patients with and without suicide attempt | At V1 (the day of the MRI) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Link between rate of Interleukin 1, 2, 4, 5, 6, 7, 9, 10, 13 and suicide attempt | Comparison of Interleukin 1, 2, 4, 5, 6, 7, 9, 10, 13 between the 3 groups | At V1 (the day of the MRI) | 
| Level of N-Acetyl-Aspartate (NAA) | Comparison of levels of NAA in the anterior cingulate cortex and the orbito-frontal cortex between the 3 groups | At V1 (the day of the MRI) | 
| Level of Choline (Cho) | Comparison of levels of Cho in the anterior cingulate cortex and the orbito-frontal cortex between the 3 groups | At V1 (the day of the MRI) | 
| Level of Myo-inositol (Myo) | Comparison of levels of Myo in the anterior cingulate cortex and the orbito-frontal cortex between the 3 groups | At V1 (the day of the MRI) | 
| Level of Creatinine (Cr) | Comparison of levels of Creatinine (Cr) in the anterior cingulate cortex and the orbito-frontal cortex between the 3 groups | At V1 (the day of the MRI) | 
| Link between level of suicidal intentionality assessed by the Columbia Suicide Severity Rating Scale (CSS-RS) and metabolites levels | Relationship between level of suicidal intentionality and Glu/Glx levels between the 3 groups | At V1 (the day of the MRI) | 
| Link between level of depression assessed by the clinician with the Hamilton Rating Scale (HAMD) and metabolite levels | Relationship between level of depression and Glu/Glx levels between the 3 groups | At V1 (the day of the MRI) | 
| Link between level of depression self assessed with the Beck Scale and metabolites levels | Relationship between level of depression and Glu/Glx levels between the 3 groups | At V1 (the day of the MRI) | 
| Link between rate of Tumor necrosis factor alpha (TNF α) and suicide attempt | Comparison of biomarkers inflammation (TNF α) between the 3 groups | At V1 (the day of the MRI) | 
| Link between rate of Tumor necrosis factor beta (TNFβ) and suicide attempt | Comparison of biomarkers inflammation (TNFβ) between the 3 groups | At V1 (the day of the MRI) | 
| Link between rate of Interferon gamma (IFNγ) and suicide attempt | Comparison of biomarkers inflammation (IFNγ) between the 3 groups | At V1 (the day of the MRI) | 
| Link between rate of C-Reactive Protein (CRP) and suicide attempt | Comparison of biomarkers inflammation (CRP) between the 3 groups | At V1 (the day of the MRI) | 
| Link between rate of Interferon Gamma Inducing Factors (IGIF)and suicide attempt | Comparison of biomarkers inflammation (IGIF) between the 3 groups | At V1 (the day of the MRI) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psychiatry, Suicidal behaviour, Cerebral metabolites, MRI, Inflammatory markers