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Recent demonstrations that ketamine, an N-methyl-D-aspartate [NMDA] receptor antagonist, can counteract suicidal ideation have increased researchers' interest in related pathways and mechanisms that might signal suicide risk. The current study concerns quinolinic acid (QUIN), an NMDA receptor agonist that is also a potent excitotoxin with proinflammatory qualities, and picolinic acid (PIC), a neuroprotective compound that antagonizes the effects of QUIN.
Both substances are formed in an enzymatic kynurenine pathway that degrades >90% of dietary tryptophan. The enzyme ACMSD (amino-β-carboxymuconate-semialdehyde-decarboxylase) determines how much kynurenine metabolism is shifted to form PIC vs. QUIN.
In two cohorts of patients who made explicit…