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

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

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.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Other: Magnetic Resonance Imaging (MRI) and biological samples

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Montpellier Hospital University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Other: Participants; 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; Participants will have to do a MRI and biological samples.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Frédéric COPPOLA, MD, Montpellier Hospital University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): November 29, 2017
• Study Completion (Actual): November 29, 2017

Study Registration Dates

• First Submitted: January 31, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: MRI; Psychiatry; Inflammatory markers; Suicidal behaviour; Cerebral metabolites
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: UF9741; 2016-A01267-44 (Other Identifier: Agence NAtionale de Sécurité du Médicament)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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