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

NCT04565834 — Completed, 849 participants, Centre Hospitalier Universitaire de Nīmes

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

Registry	NCT04565834, acronym SuiKYN
Status	Completed
Study type	Observational
Enrollment	849 (Actual)
Sponsor	Centre Hospitalier Universitaire de Nīmes (Other); collaborators: Universidad Autonoma de Madrid
Conditions	Tryptophan Metabolism Alterations, Polymorphism, Suicidal Behavior
Interventions	SNP (single nucleotide polymorphism) genotyping (Genetic)
Dates	start 2019-12-01, primary completion 2023-03-01, completion 2023-03-01, first posted 2020-09-25, last updated 2025-02-13
Locations	2 sites in France, Spain

-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.

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+Arms and interventions

Arm	Interventions	Description
: Suicide attempters	Genetic: SNP (single nucleotide polymorphism) genotyping	325 patients who have made at least one attempt to commit suicide.
Depressed non-attempters	Genetic: SNP (single nucleotide polymorphism) genotyping	99 patients suffering from depression but have never attempted to commit suicide.
Healthy controls	Genetic: SNP (single nucleotide polymorphism) genotyping	425 healthy subjects (i.e. those who have no mental disorders and have never attempted to commit suicide)

SNP (single nucleotide polymorphism) genotyping (Genetic), 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: 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.

+Outcome measures

Primary outcomes

The genotypic and allelelic frequencies of IDO1 rs7820268 SNP in each studied group [24 months]: The frequencies of this SNP will be measured as a percentage
The genotypic and allelelic frequencies of IDO2 rs10109853 SNP in each studied group [24 months]: The frequencies of this SNP will be measured as a percentage
The genotypic and allelelic frequencies of KMO rs1053230 SNP in each studied group [24 months]: The frequencies of this SNP will be measured as a percentage
The genotypic and allelelic frequencies of KAT1 rs10988134 SNP in each studied group [24 months]: The frequencies of this SNP will be measured as a percentage
The genotypic and allelelic frequencies of ACMSD rs2121337 SNP in each studied group [24 months]: The frequencies of this SNP will be measured as a percentage

Other outcomes

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

+Eligibility

Sex: All, ages: 18 Years to any, accepts healthy volunteers

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.

+Locations (2)

Facility	City	Country	Status
Department of Psychiatry, Nimes University Hospital	Nîmes, Gard	France
José-Fernandez-Piqueras	Madrid	Spain