Metabolism May Play important Role in Recurrent Major Depression

For their study, Naviaux and colleagues in The Netherlands recruited 68 subjects (45 females, 23 males) with rMDD who were in antidepressant-free remission and 59 age- and gender-matched controls. After collecting blood from patients who were in remission, the patients were followed prospectively for two-and-a-half years.

Results showed that a metabolic signature found when patients were well could predict which patients were most likely to relapse up to two-and-a-half years in the future. The accuracy of this prediction was more than 90 percent. Analysis of the most predictive chemicals found they belong to certain kinds of lipids (fats that included eicosanoids and sphingolipids) and purines.

Purines are made from molecules, such as ATP and ADP — the major chemicals used for energy storage in cells, but which also play a role in communications used by cells under stress, known as purinergic signaling.

The researchers found that in subjects with rMDD, changes in specific metabolites in six identified metabolic pathways resulted in fundamental alterations of important cellular activities.

"The findings revealed an underlying biochemical signature in remitted rMDD that set diagnosed patients apart from healthy controls," said Naviaux. "These differences are not visible through ordinary clinical assessment, but suggest that the use of metabolomics — the biological study of metabolites — could be a new tool for predicting which patients are most vulnerable to a recurrence of depressive symptoms."

The authors noted that their initial findings require validation in a larger study of at least 198 females and 198 males (99 cases and 99 controls each).