Abstract
BACKGROUND: Tryptophan, an essential precursor metabolite within the kynurenine pathway, has been implicated in the neurobiological mechanisms underlying both schizophrenia and associated suicidality. Despite this link, the lack of validated biomarkers to identify patients with dysregulated kynurenine pathway activity hinders patient stratification, thereby impeding the clinical development of pathway-targeted interventions. METHODS: This study enrolled 288 individuals diagnosed with schizophrenia (36 with prior suicide attempts, 252 without) and 202 healthy controls. Saliva samples were collected to quantify concentrations of tryptophan and associated kynurenine pathway metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Patients with a history of suicide attempts exhibited significantly elevated salivary tryptophan concentration (p = 0.006) and a reduced kynurenine/tryptophan ratio (p = 0.028) compared to patients without such a history. However, within the schizophrenia cohort, no differences in the level of kynurenine, kynurenic acid, quinolinic acid, the kynurenic-acid-to-kynurenine ratio, or the quinolinic-acid-to-kynurenic-acid ratio were observed between patients with and without a history of suicide attempts. CONCLUSIONS: The findings suggest that a history of suicide attempts is associated with alterations in salivary tryptophan concentration and the metabolic shift from tryptophan to kynurenine. These results contribute to the understanding of the potential biochemical factors involved in suicidal behavior, especially among individuals with schizophrenia. Given its non-invasive nature, monitoring salivary kynurenine metabolic shifts may serve as an early-warning biomarker for suicidal behavior.