Metabolites can be predictive markers of patients at risk for recurrent depression

Researchers at the University of California San Diego School of Medicine, in collaboration with Dutch scientists, have discovered that specific metabolites -; small molecules produced by the metabolism process -; they can be predictive markers for people at risk for major recurrent depression.

The findings were published in the online journal January 11, 2021 Psychology of translation.

This is evidence for a mitochondrial nexus at the heart of depression. It is a small study, but the first to demonstrate the ability to use metabolic markers as predictive clinical indicators of the patients at greatest risk -; and lower risk -; for recurrent strokes of major depressive symptoms. “

Robert K. Naviaux, MD, PhD, Lead Author of the Study, Professor of Medicine, Pediatrics and Pathology, UC San Diego School of Medicine

Recurrent depression (in non-clerical terms, clinical depression) is a mood disorder characterized by a combination of several symptoms: feelings of sadness or despair, anger or frustration, loss of interest, sleep disturbances, anxiety, delay or difficulty thinking, suicidal thoughts and unexplained physical problems, such as back pain or headaches.

Major depressive disorder (MDD) is among the most common mental illnesses in the United States, with an estimated life frequency of 20.6 percent, with one in five Americans suffering from at least one event during their lifetime. For patients with recurrent MDD (rMDD), the risk of five-year recurrence is up to 80 percent.

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

Results showed that a metabolic signature found when patients were well predicted which patients were most likely to go up to two and a half years in the future. The accuracy of this forecast was more than 90 percent. An analysis of the most predictable chemicals found that they belonged to specific types of lipids (fats that contained eicosanoids and sphingolipids) and purines.

Purines are made from molecules, such as ATP and ADP -; the main chemicals used for energy storage in cells, but which also play a role in communication that cells use under stress, called purinergic signals.

The researchers found that, in subjects with rMDD, changes in specific metabolites in six metabolic pathways reversed fundamental changes in important cell functions.

“The basic biochemical signature findings in rMDD revealed a retrospective submitted by confirmed patients in addition to healthy controls,” Naviaux said. “These differences are not visible through routine clinical evaluation, but they do suggest that the use of metabolomics – a biological study of metabolites – may be a new tool for predicting which patients most vulnerable to recurrence of depressive symptoms. “

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