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

NCT04565834 | Completed

• 1 other identifier: NIMAO/2019-2/JLC-01
• Study Type: observational
• Target: 849
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Tryptophan Metabolism Alterations; Polymorphism; Suicidal Behavior

Keywords

sucidal behavior; Inflammation; Kynurenines

Outcome Measures

Primary Outcomes (5)

• 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

Other Outcomes (7)

• Age of subjects

  24 months

• Gender of subjects

  24 months

• Marital status of subjects

  24 months

Study Arms (3)

: Suicide attempters

325 patients who have made at least one attempt to commit suicide.

Genetic: SNP (single nucleotide polymorphism) genotyping

Depressed non-attempters

99 patients suffering from depression but have never attempted to commit suicide.

Genetic: SNP (single nucleotide polymorphism) genotyping

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

Interventions

SNP (single nucleotide polymorphism) genotyping GENETIC

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.

Also known as: Determination of allelic and genotypic frequencies of IDO1 rs7820268, IDO2 rs10109853, KMO rs1053230, KAT1 rs10988134 and ACMSD rs2121337 SNPs in each group

: Suicide attempters; Depressed non-attempters; Healthy controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead
• Universidad Autonoma de Madrid: collaborator

Study Sites (2)

Department of Psychiatry, Nimes University Hospital

Nîmes, Gard, 30029, France

Location

José-Fernandez-Piqueras

Madrid, 28049, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

These are biological samples collected from previous registered studies (SUI-PREDICT, SMART CRISIS, SPAD) as well as samples from the Human Molecular Genetics Laboratory A-209 from the Faculty of Biology at the Independent University of Madrid, Spain.

MeSH Terms

Conditions

Inflammation

Interventions

Polymorphism, Single Nucleotide; Genotype

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polymorphism, Genetic; Genetic Variation; Genetic Phenomena

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 25, 2020
• Study Start: December 1, 2019
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: February 13, 2025

Record last verified: 2023-06

Locations

FR (1); ES (1)