State Policy Environment and Geographic Practice Preference Among Sexual and Gender Minority Medical Students.

Major depressive disorder (MDD) is increasingly recognized as an inflammatory disorder, with accumulating evidence linking immune activation to its pathogenesis. One of the principal mechanisms connecting inflammation to neuropsychiatric dysfunction is the kynurenine pathway of tryptophan metabolism, which regulates both neuroinflammatory responses and neurotransmitter homeostasis. Under physiological conditions, tryptophan serves as the precursor of serotonin, whereas inflammatory mediators, particularly interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), activate indoleamine 2,3-dioxygenase (IDO), diverting tryptophan metabolism toward kynurenine formation and consequently reducing serotonin biosynthesis. This metabolic shift has been implicated in the development and progression of depressive symptoms. Chemically, tryptophan is an aromatic amino acid possessing an indole chromophore that exhibits strong native fluorescence, whereas kynurenine, the primary product of the kynurenine pathway, displays considerably weaker fluorescence and partially overlapping emission spectra. These distinct photophysical properties make their simultaneous spectrofluorimetric determination particularly challenging, especially in complex biological matrices where endogenous constituents further compromise selectivity and sensitivity. Following its formation, kynurenine readily crosses the blood-brain barrier and undergoes further metabolism through two competing pathways. Kynurenine monooxygenase (KMO) generates quinolinic acid, a neurotoxic N-methyl-D-aspartate (NMDA) receptor agonist associated with excitotoxicity and oxidative stress, whereas kynurenine aminotransferases (KATs) produce kynurenic acid, an endogenous NMDA receptor antagonist with neuroprotective properties. Consequently, alterations in circulating tryptophan and kynurenine concentrations provide valuable biochemical indicators of kynurenine pathway dysregulation and have attracted considerable interest as potential biomarkers of MDD. Peripheral immune activation further influences central nervous system function through increased circulating kynurenine, which is transported into the brain via large neutral amino acid transporter-1 (LAT1), thereby regulating downstream neuroactive metabolite production. In addition, genetic and epigenetic alterations affecting enzymes of the kynurenine pathway, together with neuroimaging and postmortem studies, further support the involvement of this metabolic pathway in MDD pathophysiology. Accordingly, reliable simultaneous determination of tryptophan and kynurenine in biological samples is essential for investigating alterations in the kynurenine pathway and their relationship to neuroinflammation and depressive disorders.