Relationship between cortisol and tryptophan 2,3-dioxygenase in health and depression.

Sorgdrager, F. (Freek) (2014) Relationship between cortisol and tryptophan 2,3-dioxygenase in health and depression. thesis, Medicine.

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Abstract

The amino acid tryptophan precedes several physiological relevant metabolites. Proper regulation of tryptophan degradation is therefore crucial. Tryptophan 2,3-dioxygenase (TDO), regulates systemic levels of tryptophan by converting it into kynurenine. Synthetic glucocorticoids activate TDO by enhancing its transcription. Cortisol is the most important glucocorticoid in humans. This study aims to determine whether enhanced cortisol levels are associated with an increased TDO activity. Moreover, since in depression this association is possibly altered, we will compare the association in none depressed and depressed patients. 1627 participants from the Netherlands Study for Depression and Anxiety (NESDA) were included in this study and divided based on depression diagnosis. Salivary cortisol was measured by a self-test at 11:00 p.m. and serum kynurenine and tryptophan levels were used as an indicator of TDO activity. Linear regression analyses were performed adjusted for age, education, life style factors, liver function, haemoglobin and inflammation. Our analysis indicates that high cortisol levels are associated with a low kynurenine to tryptophan ratio in none depressed (β=-0.082, p < 0.05). In first episode depression a similar association is found (β=-0.096, p < 0.05), although here the association seems to be driven by tryptophan. In recurrent depression the association is strongest (β=-0.155, p < 0.05). In this association, kynurenine plays an important role. The direction of the association seems to disprove our hypothesis. We propose that, in a minor time interval, cortisol is associated with increased TDO activity. Chronically enhanced cortisol levels might however cause glucocorticoid resistance resulting in decreased TDO activity and thus a negative association. We found evidence that this phenomenon of glucocorticoid resistance might also occur in depression. We speculate that in depression, glucocorticoid resistance might also lead to low serotonin synthesis by reduced activity of the enzyme TPH, which converts tryptophan into serotonin. This might play a role in disease persistence and progression.

Item Type:	Thesis (Thesis)
Supervisor name:	Doornbos, Bennard and Kema, Ido
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:05
Last Modified:	25 Jun 2020 11:05
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2526

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