Effect of Genetic Alterations Affecting the Genes Encoding the Major Enzymes of the Kynurenine Pathway on Suicidal Behavior (SuiKYN)

Étude Des Altérations Génétiques (polymorphismes) Des Gènes-clés De La Voie Kynurénine Sur Le Comportement Suicidaire

Current research has shown that an imbalance in the Kynurenine 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 1/2, KAT (1-4), KMO and ACMSD 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 the link between these enzymes and suicidal behavior is not yet clear. The investigators hypothesize that people with history of suicide attempt would have a genetic alterations of the kynurenine pathway specific for suicidal behavior.

Study Overview

• Status: Completed
• Conditions: Suicidal Behavior; Polymorphism; Tryptophan Metabolism Alterations
• Intervention / Treatment: Genetic: SNP (single nucleotide polymorphism) genotyping

• Study Type: Observational
• Enrollment (Actual): 849

Contacts and Locations

Study Locations

• France
  • Gard
    • Nîmes, Gard, France, 30029
      • Department of Psychiatry, Nimes University Hospital
• Spain
  • Madrid, Spain, 28049
    • José-Fernandez-Piqueras

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All patients for whom biological samples have been collected and registered in the hospital's databank for the purpose of previously registered studies : SPAD (RCB no. 2016-A01375-46), SMART-CRISIS (RCB no.: 2017-A02634-49) and SUI-PREDICT (RCB no.: 2016-A00845-46) and several studies conducted at the university hospitals of Puerta de Hierro, Ramon y Cajal et Fundacion Jiminez Diaz in Madrid, Spain, since 2004.

Description

Inclusion Criteria:

• For the "Sucide attempters" group: Any patient aged 18 or over who has made at least one suicide attempt.
• For the two control groups: Any patient aged 18 or over, suffering from depression but has never attempted to commit suicide and any healthy subject who has never had any mental disorders.

Exclusion Criteria:

• Any patient who has expressed opposition to the use of his/her data.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
: Suicide attempters; 325 patients who have made at least one attempt to commit suicide.	Genetic: SNP (single nucleotide polymorphism) genotyping; We use TaqMan technique to perform SNP genotyping. The PCR reactions are carried out using the Roche "Light Cycler 480" thermal cycler following the protocol recommended by Thermo Fisher Scientific. Then, replication of 10% of the samples is carried out.; Other Names: Determination of allelic and genotypic frequencies of IDO1 rs7820268, IDO2 rs10109853, KMO rs1053230, KAT1 rs10988134 and ACMSD rs2121337 SNPs in each group
Depressed non-attempters; 99 patients suffering from depression but have never attempted to commit suicide.	Genetic: SNP (single nucleotide polymorphism) genotyping; We use TaqMan technique to perform SNP genotyping. The PCR reactions are carried out using the Roche "Light Cycler 480" thermal cycler following the protocol recommended by Thermo Fisher Scientific. Then, replication of 10% of the samples is carried out.; Other Names: Determination of allelic and genotypic frequencies of IDO1 rs7820268, IDO2 rs10109853, KMO rs1053230, KAT1 rs10988134 and ACMSD rs2121337 SNPs in each group
Healthy controls; 425 healthy subjects (i.e. those who have no mental disorders and have never attempted to commit suicide)	Genetic: SNP (single nucleotide polymorphism) genotyping; We use TaqMan technique to perform SNP genotyping. The PCR reactions are carried out using the Roche "Light Cycler 480" thermal cycler following the protocol recommended by Thermo Fisher Scientific. Then, replication of 10% of the samples is carried out.; Other Names: Determination of allelic and genotypic frequencies of IDO1 rs7820268, IDO2 rs10109853, KMO rs1053230, KAT1 rs10988134 and ACMSD rs2121337 SNPs in each group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The genotypic and allelelic frequencies of IDO1 rs7820268 SNP in each studied group	The frequencies of this SNP will be measured as a percentage	24 months
The genotypic and allelelic frequencies of IDO2 rs10109853 SNP in each studied group	The frequencies of this SNP will be measured as a percentage	24 months
The genotypic and allelelic frequencies of KMO rs1053230 SNP in each studied group	The frequencies of this SNP will be measured as a percentage	24 months
The genotypic and allelelic frequencies of KAT1 rs10988134 SNP in each studied group	The frequencies of this SNP will be measured as a percentage	24 months
The genotypic and allelelic frequencies of ACMSD rs2121337 SNP in each studied group	The frequencies of this SNP 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age of subjects	The age will be recorded for statistical purposes	24 months
Gender of subjects	The gender will be recorded for statistical purposes	24 months
Marital status of subjects	The marital status will be recorded as a number and a percentage	24 months
Education level of subjects	the education level will be recorded as a number and a percentage	24 months
Diagnosis	The diagnosis will be recorded as a number and a percentage	24 months
Number of suicide attempts	The number of suicide attempts will be recorded as a number	24 months
Age of first suicide attempt	Age of first suicide attempt will be recorded as a number	24 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: Universidad Autonoma de Madrid

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; sucidal behavior; Kynurenines
• Other Study ID Numbers: NIMAO/2019-2/JLC-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No