Abstract
Immune-mediated inflammatory processes and oxidative stress are involved in the aetiopathogenesis of bipolar disorder (BD) and weight-associated comorbidities. Tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) along the kynurenine axis concomitant with a pro-inflammatory state was found to be more active in BD, and associated with overweight/obesity. This study aimed to investigate tryptophan metabolism in BD compared to controls (C), stratified by weight classes, in a longitudinal setting, dependent on the incidence of BD episodes. Peripheral tryptophan, kynurenine, and neopterin were assessed in the serum of 226 BD individuals and 142 C. Three samples in a longitudinal assessment were used for 75 BD individuals. Results showed a higher kynurenine/tryptophan in both BD compared to C and overweight compared to normal weight persons. Levels remained stable over time. In the longitudinal course, no differences were found between individuals who were constantly euthymic or not, or who had an illness episode or had none. Findings indicate that tryptophan, kynurenine, and IDO-1 activity may play a role in pathophysiology in BD but are not necessarily associated with clinical manifestations. Accelerated tryptophan breakdown along the kynurenine axis may be facilitated by being overweight. This may increase the risk of accumulation of neurotoxic metabolites, impacting BD symptomatology, cognition, and somatic comorbidities.
Highlights
In the MANCOVA, using both group and weight as between subject factors, we found a significant difference in kynurenine with higher levels of overweight individuals than normal weights
Summarizing, this study proved the presence of increased tryptophan catabolism along the kynurenine axis in bipolar disorder (BD), most likely due to immune-mediated activation of IDO1 as the increased kynurenine to tryptophan ratio correlated with elevated neopterin concentrations
The present study investigated the tryptophan metabolism in BD, displaying higher kynurenine and kynurenine/tryptophan as a proxy for IDO-1 activity than in C and higher levels in overweight persons than in normal weight individuals
Summary
Bipolar disorder (BD) is a chronic and lifelong psychiatric illness characterized by recurrent depressive and manic or hypomanic episodes. Diagnosis and treatment considerations are solely based on clinical phenomenology while objective biomarkers are insignificant. Identifying biomarkers that provide evidence about the current stage of illness and predict the further course of the disease is an essential endeavor in BD research. Neurotransmitter imbalances, epigenetics, chronic and acute psychosocial stressors as well as oxidative stress, inflammatory and immune processes are vital
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