Clinical trial NCT02855918: Blood Biomarkers in Suicidal Behaviour
Official title: Modification of the Expression of ADARs and PDE8A Editing in Suicidal Behavior
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depression
Keywords: Psychiatry
Depressive disorder
Suicidal behavior
Genetics
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: Sys2Diag, Mixt laboratory CNRS/Alcediag, Montpellier
First posted: 2016-08-04
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Suicidal behavior (SB) is a major public health problem in France, with more than 10,000 suicides and 220,000 suicide attempts per year.

According to the commonly accepted model for understanding suicidal behavior, individuals who carry a suicidal act when subjected to stress factors (environmental stress, depression, substance ...) are those which have a specific vulnerability.

These vulnerabilities can be considered as clinical parameters (propensity to despair, aggressive and/or impulsive traits), neurobiological parameters (dysfunction of the serotonergic system, ...) and cognitive parameters (taking disadvantageous decision ...). Suicidal vulnerability is partly underpinned by genetic factors. The interest of current researches is to identify biomarkers that will improve the opportunities for early identification of subject with a risk for SB. Numerous scientific studies, including post-mortem studies of the brains of suicide completers, have established a link between dysregulation of the ribonucleic acids editing (RNA) of certain genes, the enzymatic activity of Adenosine deaminases acting on RNA (ADARS) responsible for this edition and suicidal behavior. A prospective study is needed to quantify and qualify in the blood of depressed patients (with or without a history of suicide) and healthy controls, the editing changes and the expression and alteration of the activity of ADARS.

Detailed description: Over two years, 600 participants will be recruited:

* 225 subjects with current major depressive episode and an history of suicide attempt (depressed suicide attempters)
* 225 subjects with current major depressive episode but with no personal history of suicide attempt (affective controls)
* 150 subjects with no history of psychopathology whole life (healthy controls)

Each patient will attend a total of 3visits during a follow-up period of 6 months +/- 15 days (inclusion, visit at 3 and 6 months).

Eligibility criteria: No specific inclusion criteria :

* 18 to 65 years
* Subject who signed the informed consent
* Able to understand the nature, purpose and methodology of the study
* Able to understand and perform the clinical and neuropsychological evaluations.

Specific inclusion criteria depressed suicide attempters:

* Subject whose primary psychiatric diagnosis is a major depressive episode according to Diagnostic and Statistical Manual of Mental Disorders -5 (DSM-5) criteria
* Personal history of suicide attempt

affective controls:

* Subject whose primary psychiatric diagnosis is a major depressive episode according to DSM-5 criteria
* No personal history of suicide attempt

healthy controls:

* No personal history of psychiatric disorders (Axis I ) defined by the Mini International Neuropsychiatric Interview (MINI) according to the DSM-5 criteria
* No history of suicide attempt

Exclusion criteria

* Refusal of participation
* Deprived of liberty Subject (by judicial or administrative decision)
* Subject protected by law (guardianship)
* Subject exclusion period in relation to another protocol
* Subject is not affiliated to a social security scheme, beneficiary or not such a plan
* Subject for which the maximum annual amount of allowances of € 4,500 has been reached
* Pregnant women
* Breastfeeding Women

Primary outcomes:
measure: Evolution of the modification of the expression of Adenosine deaminases acting on RNA (ADARs) and of the editing profile of phospho-diesterase 8A (PDE8A)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
Secondary outcomes:
measure: Modification of the expression of ADAR1a enzymes
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Spindle And Kinetochore Associated protein 2 (SKA2)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression of ADAR1b enzymes
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression of ADAR2 enzymes
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Interleukins (ILs)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Chemokines (CXCLs)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Brain derived Neurotrphic factor (BDNF)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Cluster of differentiation 24 (CD24)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Three prime repair exonuclease 1 (TREX1)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Interferon stimulated gene 15 (ISG15)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Tumor necrosis factor alpha (TNF alpha)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Vascular endothelial growth factor (VEGF)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of Hydroxytryptamine receptor 2A (HTR2A)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
measure: Modification of the expression and RNA editing of insulin-like growth factor protein 7 (IGFB7)
timeFrame: At the inclusion visit, 3 months and 6 months after the inclusion
Other outcomes:
Locations:
city: Montpêllier
country: France
facility: University Hospital
Study officials:
References: