Genetic association of the kynurenine pathway to suicidal behavior
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Bibliographic record
Abstract
Suicidal behavior has been associated with dysfunctions in the kynurenine pathway, including alterations in the levels of neuroprotective and neurotoxic metabolites. Changes in the catalytic activity of enzymes within the pathway may contribute significantly. Variations in the genes encoding enzymes within the pathway can significantly affect their catalytic activity, playing a crucial role in the process. To explore this possibility, we hypothesized that these genetic variations would occur more frequently in patients with a history of suicidal behavior compared to non-suicidal individuals. Thus, we investigated the relationship between a history of suicide attempts and five single nucleotide polymorphisms (SNPs) within genes involved in the kynurenine pathway: IDO1 (rs7820268), IDO2 (rs10109853), KMO (rs1053230), KAT1 (rs10988134), and ACSMD (rs2121337). Our sample comprised 849 subjects: 325 individuals who had attempted suicide in their lifetime (SAs), 99 individuals with a history of major depression disorder but no previous suicide attempts (non-SAs), and 425 non-psychiatric controls (CTRL). We performed SNP association analyses using codominant, dominant, and recessive models. Adjustment for sex and multiple comparisons was applied. After adjustment, the analysis revealed that SAs showed a significantly higher frequency of T alleles and TT genotypes of the rs1053230 SNP compared to CTRL across nearly all models. Furthermore, in the recessive model, non-SAs displayed a higher prevalence of the TT genotype of the rs10109853 SNP compared to CTRL. The rs1053230 and rs10109853 SNPs could play a role in the previously observed metabolic dysregulation among SAs and non-SAs, respectively. To validate our findings, it is crucial to conduct functional analyses to investigate the impact of rs10109853 and rs1053230 SNPs on the expression and/or catalytic activity of the corresponding enzymes. • Kynurenine pathway genetics may impact mood and suicidal risk. • Suicide attempters had more T alleles in a critical enzyme SNP than controls. • Another SNP was associated with a history of major depression. • Functional analyses on genetic variants of the KYN pathway are warranted.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it