The role and mechanism of tryptophan – kynurenine metabolic pathway in depression

Abstract

Major depressive disorder (MDD) is a common mental illness characterized by persistent low mood and anhedonia, normally accompanied with cognitive impairment. Due to its rising incidence and high rate of recurrence and disability, MDD poses a substantial threat to patients’ physical and mental health, as well as a significant economic cost to society. However, the etiology and pathogenesis of MDD are still unclear. Chronic inflammation may cause indoleamine-2,3-dioxygenase (IDO) to become overactive throughout the body and brain, resulting in excess quinolinic acid (QUIN) and less kynuric acid (KYNA) in the brain. QUIN’s neurotoxicity damages glial cells and neurons, accelerates neuronal apoptosis, hinders neuroplasticity, and causes depression due to inflammation. Therefore, abnormal TRP-KYN metabolic pathway and its metabolites have been closely related to MDD, suggesting changes in the TRP-KYN metabolic pathway might contribute to MDD. In addition, targeting TRP-KYN with traditional Chinese medicine showed promising treatment effects for MDD. This review summarizes the recent studies on the TRP-KYN metabolic pathway and its metabolites in depression, which would provide a theoretical basis for exploring the etiology and pathogenesis of depression.

SCFAs Supplementation Rescues Anxiety- and Depression-like Phenotypes Generated by Fecal Engraftment of Treatment-Resistant Depression Rats

“…Elevated plasma kynurenine and quinolinic acid levels positively correlate with depression. 72,73 Our results suggest that the SCFAs can modulate the plasma levels of tryptophan metabolites, which may be ascribed to the anxiolytic-and antidepressant-like effects in rats. Healthy intestinal microbiota and their metabolites play an important role in maintaining the gut ecosystem in the host.…”

Copper(ii) phthalocyanine as an electrocatalytic electrode for cathodic detection of urinary tryptophan

“…3 Given the human body's inability to independently synthesize tryptophan, its levels are intricately regulated through external sources, including diet and medications. Recent studies reveal that abnormal tryptophan levels in biological fluids may serve as potential biomarkers for conditions such as depression, [4][5][6] multiple sclerosis, 7,8 schizophrenia, 9,10 autism spectrum disorder, [11][12][13] epilepsy, 14 bipolar disorder, 1,2 and cancer. 3,[15][16][17] Consequently, there has been a notable surge in the demand for tryptophan analysis, highlighting its growing importance in diagnosing and understanding various medical conditions.…”

Polypyrimidine tract binding protein knockdown reverses depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons

“…Multiple types of neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease (AD), and major depressive disorder (MDD), afflict the elderly, leading to a huge burden on public health ( Rauf and Rahman, 2022 ; Suzuki et al, 2022 ). MDD has become the most common mental disease ( Clevenger et al, 2018 ), manifests typically as a persistently low mood and lack of pleasure, often accompanied by cognitive impairment ( Gong et al, 2023 ). At present, various antidepressants have been developed to improve a patient’s condition ( Cipriani et al, 2009 ), and cognitive behavioral therapy has also been used ( Wang et al, 2022 ).…”