Effect of Genetic Alterations in Key Genes in the Kynurenine Pathway on Suicidal Behavior

Study Overview
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Brief Summary
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Current research has shown that an imbalance in the Kinurenine pathway plays a role in the physiopathology of neurogenerative and mental disorders (with a decrease in neuroprotective metabolites and an increase in neurotoxic products). So far the research has concentrated on the enzymes IDO, KAT, KMO, 3HAO and QPRT which are the key players in this pathway. Several polymorphisms affecting these enzymes have been associated with certain disorders characterized by a deregulation of the inflammation and immune response (McCauley et al 2009,Tardito et al 2013, Lee et al 2014), but no studies have ever tried to find a link between these enzymes and suicidal behavior. The investigators hypothesize that people who have attempted to commit suicide will have pro-inflammatory genetic variations affecting the kynurenine pathway.

Official Title
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A Study on Genetic Alterations (Polymorphism) in Key Genes in the Kynurenine Pathway on Suicidal Behavior

Conditions
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Kynureninase, Polymorphism, Suicidal Behavior

Intervention / Treatment
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* Genetic: Analysis of Single nucleotide polymorphisms in each group.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For the Suicide group: Any patient aged 18 or over who has made at least one suicide attempt. For the control group: Any patient aged 18 or over, suffering from depression but has never attempted to commit suicide and any healthy patient who has never had any mental disorders. Exclusion Criteria: Any patient who has expressed opposition to the use of his/her data.

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Suicidal patients<br>Patients who have made at least one attempt to commit suicide. | Genetic: Analysis of Single nucleotide polymorphisms in each group.<br>* The 6 single nucleotide polymorphisms (SNPs) determined will then be genotyped according to the Thermofisher Taqman technique ona 480 LightCycler (Roche Applied Science). 10% of the genotypes will be confirmed via Sanger sequencing on a 3500xl Thermofisher sequencer according to the manufacturer's recommendations.<br>* Other names: Determination of frequency of IDO1 rs 9657182, IDO1 rs35059413, IDO2 rs2929115, IDO2 rs2929116, KMO rs1053230, KMO rs2275163 for each group of patients.;|
| Control group<br>This group will consist of two types of people: 75 healthy subjects (i.e. those who have no mental disorders and have never attempted to commit suicide) and 150 patients suffering from depression but have never attempted to commit suicide. | Genetic: Analysis of Single nucleotide polymorphisms in each group.<br>* The 6 single nucleotide polymorphisms (SNPs) determined will then be genotyped according to the Thermofisher Taqman technique ona 480 LightCycler (Roche Applied Science). 10% of the genotypes will be confirmed via Sanger sequencing on a 3500xl Thermofisher sequencer according to the manufacturer's recommendations.<br>* Other names: Determination of frequency of IDO1 rs 9657182, IDO1 rs35059413, IDO2 rs2929115, IDO2 rs2929116, KMO rs1053230, KMO rs2275163 for each group of patients.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of single nucleotide polymorphism rs9657182 of Enzyme IDO1 in the Suicide group | The presence of this genetic variation will be measured as a percentage | 24 months | 
| Presence of single nucleotide polymorphism rs9657182 of Enzyme IDO1 in the Emotion Control group | The presence of this genetic variation will be measured as a percentage | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A. Frequency of single nucleotide polymorphism rs35059413 of Enzyme IDO1 in the Suicide group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs35059413 of Enzyme IDO1 in the Emotion Control group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs2929115 of Enzyme IDO2 in the Suicide group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs2929115 of Enzyme IDO2 in the Emotion Control group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs2929116 of Enzyme IDO2 in the Suicide group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs2929116 of Enzyme IDO2 in the Emotion Control group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs1053230 of KMO in the Suicide group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs1053230 of KMO in the Emotion Control group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs2275163 of KMO in the Suicide group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| A. Frequency of single nucleotide polymorphism rs2275163 of KMO in the Emotion Control group | The frequency of this genetic variation will be measured as a percentage | 24 months | 
| B. Simultaneous influence of the various single nucleotide polymorphisms on the functioning of the kynurenine pathway and suicidal behavior. | The numerical value of the polygenic risk score will be used to measure this criterion. | 24 months | 
| C. Percentage frequency of single nucleotide polymorphisms among patients in the Suicide group. | The frequency of single nucleotide polymorphisms, measured as a percentage, will be compared with the number of suicide attempts, the lethality, the method used and the intensity of suicidal ideation in the Suicide group. The polygenic risk score is calculated as a weighted sum of the risk alleles resulting from the study using GWAS (genome-wide association study) summary statistics data. This score is not calculated on a scale but as a relative risk compared to the unaffected population. | 24 months | 
| D. Correlation between negative life events triggering suicide attempts and the level of inflammation in the Suicide group. | Inflammation will be measured according to the level of the main pro-inflammatory cytokines in the various samples : TGF-beta. The rate of anti-inflammatory cytokines IL-2 and IL-4 will also be measured in pg/ml and mg/ml | 24 months | 
| D. Correlation between negative life events triggering suicide attempts and the level of inflammation in the Affective Controls group. | Inflammation will be measured according to the level of the main pro-inflammatory cytokines in the various samples : TGF-beta. The rate of anti-inflammatory cytokines IL-2 and IL-4 will also be measured in pg/ml and mg/ml | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Suicide, Inflammation, Kynurenine