Indoleamine-2,3-dioxygenase and physical activity in bipolar disorder

Alterations in the tryptophan (TRP)-kynurenine (KYN) metabolism play an important role in the aetiopathogenesis of bipolar disorder (BD) and its obesity-related comorbidities. Physical activity has been suggested as a potential modulator of the indoleamine-2,3-dioxygenase, which regulates the metabolism of TRP towards KYN. This cross-sectional study explored differences in the KYN/TRP ratio, a proxy for indoleamine-2,3-dioxygenase, between patients with BD and healthy controls, stratified by level of physical activity. A total of 139 patients with BD and 76 controls were included. Physical activity was assessed using the International Physical Activity Questionnaire, and serum TRP and KYN levels were measured. Group differences in the KYN/TRP ratio depending on the level of physical activity (low-moderate, high) were examined using ANCOVA, controlling for age, sex, and body mass index (BMI). Results showed a significantly higher KYN/TRP ratio in patients with BD than in controls in the unadjusted comparison. After adjusting for sex, age and BMI, no statistically significant difference was observed in the KYN/TRP ratio for either group or for level of physical activity. In contrast, the interaction between age and group was significant, indicating that the age-related increase of the KYN/TRP ratio was stronger in patients with BD than in controls. However, this finding should be interpreted with caution and be considered as hypothesis-generating. The findings of the unadjusted data support previous results of altered TRP metabolism in BD but indicate that physical activity alone may not sufficiently modulate the KYN/TRP ratio. Future studies should consider longitudinal study designs, objective measures of physical activity and KYN downstream metabolites. Despite these findings, physical activity should remain a key component in the multimodal treatment of BD due to its benefits for physical and mental health.