Researchers have found that certain metabolites — small molecules produced by the process of metabolism — may be the predictive indicators for persons at risk of recurrent major depressive disorder (RMMD). The findings, published in the journal Translational Psychiatry, indicated that the accuracy of this prediction was more than 90 per cent. “This is evidence for a mitochondrial nexus at the heart of depression,” said the researcher, Robert K. Naviaux, a professor at University of California in San Diego. “It’s a small study, but it is the first to show the potential of using metabolic markers as predictive clinical indicators of patients at greatest risk — and lower risk — for recurring bouts of major depressive symptoms,” Naviaux added.

rMMD is a mood disorder characterised by multiple symptoms in combination — feelings of sadness or hopelessness, anger or frustration, loss of interest, sleep disturbances, anxiety, slowed or difficulty thinking, suicidal thoughts and unexplained physical problems, such as back pain or headaches.

For the study, the team 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.

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 rMMD, changes in specific metabolites in six identified metabolic pathways resulted in fundamental alterations of important cellular activities.