People with major depressive disorder (MDD) have an altered purine metabolism, which may be a defense mechanism against increased oxidative stress in depression, according to a study published online April 30, 2016 in Psychoneuroendocrinology.
Previous research has linked altered metabolic activity of the purine cycle with systemic responses related to depression, such as increased pro-inflammatory and oxidative processes. Notably, depression is characterized by a compromised state of oxidative stress.
For this study, the researchers hypothesized that people with MDD have distinct purine metabolite profiles compared with patients without depression.
To find out, they collected serum samples from 99 patients with MDD and 253 non-depressed controls, aged 20-71 years. After adjusting for age, gender, smoking, alcohol use, and other factors, the researchers analyzed the samples and looked for differences between patients with MDD and the controls.
“Out of the purine metabolites we analyzed, the concentrations of inosine and guanosine were lower, and the concentrations of xanthine were higher in people with depression than in healthy persons,” said the study’s first author Toni Ali-Sisto, a PhD student at the University of Eastern Finland’s Institute of Clinical Medicine, in Kuopio, Finland.
This suggests that circulating xanthine may accumulate in patients with MDD, which may occur due to increased degradation of inosine and guanosine, which were lower in the MDD group compared to the control group, the researchers noted.
Xanthine helps produce uric acid—the end product of purine metabolism. Uric acid is also an antioxidant that combats the adverse effects of oxidative stress. This falls in line with previous studies that reported low levels of uric acid in people with depression.
“The increased activity of the purine cycle may represent a compensatory mechanism that seeks to supply a sufficient level of uric acid to counteract increased oxidative processes during depression,” the authors wrote.
The levels of several purine metabolites changed significantly during the follow-up period in the MDD group. Interestingly, however, the use of antidepressants or antipsychotics did not affect the concentrations of purine metabolites. Further studies will need to clarify the relationship, if any, between therapeutic intervention and purine metabolism, the researchers wrote.