The Neurochemistry of Depression: The Good, The Bad and The Ugly

A large constellation of experimental evidence suggests that neuroinflammation is involved in the onset of depression and neurodegenerative disorders. Many studies have shown impairments in tryptophan metabolism, the major pathway for the synthesis of serotonin, the mood regulating neurotransmitter. This article reviews the various metabolites generated in the competing pathways of tryptophan metabolism including the kynurenine pathway. Increased synthesis of the neurotoxic compound quinolinic acid occurs at the expense of the synthesis of the neuroprotective metabolite kynurenic acid. This shift in equilibrium plays a critical role in the induction of oxidative stress, neuroinflammation, and neurotoxicity. Sufficient protein intake with adequate amounts of tryptophan along with dietary antioxidants and flavonoids may offer protection against major depressive and neurodegenerative disorders.