Systemic inflammation and increased tryptophan catabolism underpin depression, anxiety, and chronic fatigue symptoms after myocardial infarction: effects of revascularization

BackgroundPatients with myocardial infarction (MI) often exhibit neuropsychiatric symptoms, but the underlying pathophysiological mechanisms remain elusive. This study examines the roles of the tryptophan catabolite (TRYCAT) pathway, systemic inflammation, and adverse metabolic remodeling in this comorbidity, both before and after percutaneous coronary intervention (PCI). MethodsWe assessed depression, anxiety, and chronic-fatigue syndrome (CFS)-like rating scales, blood levels of TRYCATs, inflammatory markers, and human fatty acid binding protein (h-FABP)4 in MI patients both before and after PCI and in healthy controls. ResultsMI patients exhibited significantly higher neuropsychiatric symptoms, a pro-inflammatory shift, TRYCAT pathway changes, and increased h-FABP4. The TRYCAT profile exhibited a bias towards neurotoxicity, characterized by elevated levels of 3-hydroxykynurenine and quinolinic acid and decreased kynurenic acid. Binary logistic regression revealed that a model using TRYCATs, immune data (e.g., neutrophil/lymphocyte ratio), and h-FABP4 distinguished post-MI patients from healthy controls with 92% cross-validated accuracy. A large part of the variance (around 60%) in the neuropsychiatric scores was explained by immune-metabolic data, higher neurotoxic and lower neuroprotective TRYCATs. PCI significantly improved neuropsychiatric symptoms, TRYCAT pathway-associated neuroprotection, the immune-inflammatory response, and h-FABP4. ConclusionMI is linked to increased TRYCAT-associated neurotoxicity and adverse inflammatory-metabolic remodeling in association with heightened depression, anxiety, and CFS-like symptoms. The reduction in immune activation, the normalization of neurotoxic TRYCAT synthesis, and reversal of adverse metabolic-inflammatory signaling following PCI may explain the observed improvement in neuropsychiatric symptoms following coronary revascularization.