Tryptophan-Based Imaging Agents for Major Depressive Disorders

Major depressive disorder (MDD) is one of the most prevalent mental diseases; early intervention and treatment are crucial. Unfortunately, the complexity of this disorder makes timely intervention challenging. A clear understanding of the biochemical mechanisms in depression will benefit the diagnosis, stratification, and treatment of prevalent mental disorders. One chemical pathway that has attracted interest is the kynurenine (KYN) pathway, which plays several complex roles in the human body, including regulating immune and inflammatory responses. Dysregulated tryptophan metabolism is widely involved in neuropsychiatric disorders, including depression. Decreased tryptophan and its metabolites and the imbalance between the neuroprotective and neurotoxic arms of the KYN pathway are consistently found in patients with major depression. Tryptophan-based radiotracers provide valuable information in studying whole-body tryptophan depletion-related depression and antidepressant mechanisms. Understanding the relationship between the peripheral and central KYN pathway and the biological mechanisms underlying the heterogeneous symptoms with functional imaging in depression is a pivotal part of enhancing potential patient stratification, developing effective diagnostic tools for subtypes, guiding personalized drug development, and improving treatment strategies. We review tryptophan-based radiopharmaceuticals in the study of depression. We summarize the key findings, noting both broad consensus and inconsistencies, as well as limitations. Finally, we offer our perspective on the future development of tryptophan radiopharmaceuticals in guiding depression diagnosis, targeted interventions, treatment evaluation, and drug development in these prevalent mental disorders.