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Abstract
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.
Kami Pearson, MS, is a Research Associate, Kimberley Beier, BS,
Thornton Mardis, MA, and Bryan Munoz, MS, are medical students, and Asma Zaidi, PhD, (pictured), is a Professor of Biochemistry. All are at Kansas City University, Kansas City, Missouri.
This article reviews the various metabolites generated in the competing pathways of tryptophan metabolism including the kynurenine pathway.
Depression
Depression, aka major depressive disorder (MDD), is recognized as a leading cause of disability worldwide, with 350 million people affected as of 2019,an increase of 18% over the last decade.1 Approximately one in five individuals will experience a major depressive episode during their lifetime. Women are affected by depression at rates nearly twice that of men.2 The economic burden of MDD, estimated at $236 billion in 2010, showed a steep 40% increase to $326 billion in 2018.3 Depression occurs on a spectrum and is a complex disorder with a wide array of symptoms and clinical features that may require unique treatments. Clinical presentations include depressed mood, anhedonia, insomnia, appetite or weight changes, anergia, psychomotor or neurocognitive dysfunction, and most notably, suicidal ideation.2 Over the last decade, major advancements have been made in elucidating the etiology of depression. The role of serotonin continues to be studied, and inflammation is now understood as a major player in the development of depression. It is clear that depression is a heterogeneous disease, with distinct biochemical features underlying each subtype. Emerging new evidence challenges existing assumptions of the key players that contribute to the development of depression and the severity of symptoms.