Exercising control over runaway kynurenine pathway metabolism: Towards improved treatment outcomes in major depression

We all know someone who suffers from depression, the difficulties they experience before being diagnosed and the hardship endured before an effective medication that improves their symptoms is finally found. Often, despite multiple trials of different medications, the symptoms of depression persist. In addition to the personal and societal consequences of depression, this is also a costly process for the Irish healthcare system.

Exercise has shown some potential to improve treatment outcomes in depression but uptake of this option is low due to a poor understanding of how these beneficial effects are produced. Increased metabolism of tryptophan along the kynurenine pathway is a feature of depression linked to mood and cognition. Recent preclinical studies suggest that exercise limits the adverse impact of this altered profile of tryptophan metabolism. In this proposal, we will evaluate the ability of exercise to produce similar effects in human subjects and establish whether this is the mechanism underlying its beneficial effects in major depression.

Healthy controls subjects will be used to define the optimal level of exercise required to beneficially alter kynurenine pathway metabolism by measuring a complete profile of circulating tryptophan degradation products before and after a supervised exercise schedule. Standardised rating scales and computer-based cognitive testing will be employed to monitor associated exercise-induced improvements in symptom severity in a depressed cohort. A statistical approach will then be taken to examine the interaction between these parameters. This will help improve patient care by increasing the uptake and prescription of exercise for the management of depression and will also help identify new targets for the development of faster acting more effective drugs. The outcomes of this research offer economic and societal benefits in addition to the essential improvements in patient care which are so urgently required.

Award Date: 29 June 2017
Award Value: €369573
Principal Investigator: Dr Gerard Clarke
Host Institution: University College Cork
Scheme: Investigator Led Projects