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.