Abstract
A recent study--comparing those with depression, somatization, comorbid depression+somatization, and controls--showed specific changes in the tryptophan catabolite (TRYCAT) pathway in somatization, specifically lowered tryptophan and kynurenic acid, and increased kynurenine/kynurenic acid (KY/KA) and kynurenine/tryptophan ratios. These findings suggest that somatization and depression with somatization are characterized by increased activity of indoleamine 2,3-dioxygenase and disorders in kynurenine aminotransferase activity, which carry a neurotoxic potential. This chapter reviews the evidence that the TRYCAT pathway may play a pathophysiological role in the onset of somatization and depression with somatization and, furthermore, suggests treatment options based on identified pathophysiological processes. Lowered plasma tryptophan may be associated with enhanced pain, autonomic nervous system responses, gut motility, peripheral nerve function, ventilation, and cardiac dysfunctions. The imbalance in the KY/KA ratio may increase pain, intestinal hypermotility, and peripheral neuropathy through effects of KY and KA acid, both centrally and peripherally, at the N-methyl-d-aspartate receptor (NMDAR), G-protein-coupled receptor-35 (GPR35), and aryl hydrocarbon receptor (AHr). These alterations in the TRYCAT pathway in somatization and depression may interface with the role of the mu-opioid, serotonin, and oxytocin systems in the regulation of stress reactions and early attachment. It is hypothesized that irregular parenting and insecure attachment paralleled by chronic stress play a key role in the expression of variations in the TRYCAT pathway-both centrally and peripherally-driving the etiology of somatization through interactions with the mu-opioid receptors. Therefore, the TRYCAT pathway, NMDARs, GPR35, and AHrs may be new drug targets in somatization and depression with somatizing. We lastly review new pathophysiologically driven drug candidates for somatization, including St. John's wort, resveratrol, melatonin, agomelatine, Garcinia mangostana (γ-mangostin), N-acetyl cysteine, and pamoic acid.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Advances in Protein Chemistry and Structural Biology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
