Peripheral serotonin-kynurenine pathway alterations and their associations with symptom severity in post-traumatic stress disorder: An exploratory case-control study.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been associated with alterations in peripheral tryptophan metabolism and disturbances in serotonin-kynurenine pathways. However, findings regarding peripheral kynurenine-related measures in PTSD remain inconsistent, and their relationships with symptom severity are incompletely understood. This study investigated peripheral serotonin-tryptophan-kynurenine pathway alterations in PTSD and explored their relationships with clinical symptom burden.

METHODS: In this exploratory cross-sectional case-control study, 60 adults with DSM-5 PTSD and 41 age- and sex-matched healthy controls were enrolled. PTSD diagnosis was confirmed using the Structured Clinical Interview for DSM-5 (SCID-5), and symptom severity was assessed using the Impact of Event Scale-Revised (IES-R). Fasting morning serum samples were analyzed using commercially available ELISA kits to quantify peripheral serotonin-kynurenine pathway measures. Group comparisons, correlation analyses, and logistic regression analyses were performed.

RESULTS: Compared with healthy controls, patients with PTSD demonstrated lower peripheral serotonin concentrations together with higher kynurenine levels, kynurenine/tryptophan (Kyn/Trp) ratios, and elevations in several downstream kynurenine-related measures (all p < 0.05). Among all measured biochemical variables, serum kynurenine demonstrated the strongest positive associations with IES-R total scores and multiple symptom dimensions within the PTSD group. Kyn/Trp ratio, 3-hydroxykynurenine, and quinolinic acid were also positively associated with symptom severity measures. In multivariable analyses, lower serotonin levels remained independently associated with PTSD status.

CONCLUSIONS: PTSD was associated with broad peripheral alterations in serotonin-tryptophan-kynurenine pathway measures, and several kynurenine-related indices were linked to dimensional symptom burden. In particular, serum kynurenine concentrations demonstrated strong associations with PTSD symptom severity, suggesting that altered peripheral tryptophan metabolism may accompany clinically relevant symptom heterogeneity in PTSD. Given the exploratory cross-sectional design and peripheral nature of the measurements, replication using longitudinal cohorts and analytically validated metabolomic approaches is warranted.