Metabolism may play a role in recurrent major depression

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Researchers at the University of California San Diego School of Medicine, working with Dutch scientists, have found that certain metabolites – small molecules produced by the process of metabolism – may be predictive indicators for those at risk. recurrent major depressive disorder.

The results were published in the January 11, 2021 online issue of Translational Psychiatry.

“This is evidence of a mitochondrial link to the heart of depression,” said senior author Robert K. Naviaux, MD, PhD, professor of medicine, pediatrics and pathology at UC San Diego School of Medicine. “It’s a small study, but it’s the first to show the potential to use metabolic markers as clinical predictors of patients at highest risk – and lowest risk – for recurrent episodes of major depressive symptoms. ”

Robert Naviaux, MD, Ph.D.

Recurrent major depressive disorder (in simple terms, clinical depression) is a mood disorder characterized by multiple associated symptoms: feelings of sadness or hopelessness, anger or frustration, loss of interest, sleep disturbances, anxiety, slowing down or difficulty thinking, suicidal thoughts, and unexplained physical problems, such as back pain or headaches.

Major depressive disorder (MDD) is one of the most common mental illnesses in the United States, with an estimated lifetime prevalence of 20.6%, which means that one in five Americans will suffer from at least one episode in his life. For patients with recurrent MDD (rMDD), the risk of recurrence over five years can be as high as 80%.

For their study, Naviaux and colleagues in the Netherlands recruited 68 subjects (45 women, 23 men) with rMDD who were in remission without antidepressants and 59 controls of the same age and sex. After collecting blood from patients in remission, the patients were followed prospectively for two and a half years.

The results showed that a metabolic signature found when patients were healthy could predict which patients were most likely to relapse for up to two and a half years in the future. The accuracy of this prediction was over 90 percent. Analysis of the most predictive chemicals revealed that they belonged to certain types of lipids (fats which included 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 the communications used by cells in situation. 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 in important cellular activities.

“The results revealed an underlying biochemical signature in rMDD in remission that distinguishes diagnosed patients from healthy controls,” Naviaux said. “These differences are not visible on a routine clinical evaluation, but suggest that the use of metabolomics – the biological study of metabolites – may be a new tool to predict which patients are most vulnerable to symptom recurrence. depressive. “

The authors noted that their initial results require validation in a larger study involving at least 198 women and 198 men (99 cases and 99 controls each).

Co-authors include: Roel JT Mocking, Caroline A. Figueroa and Johanna Assies, University of Amsterdam, The Netherlands; Jane C. Naviaux, Kefeng Li, Lin Wang, Jonathan M. Monk and A. Taylor Bright, UC San Diego; Aart H. Schene, Radboud University Medical Center, The Netherlands; and Henricus G. Ruhe, University of Amsterdam and Radboud University Medical Center, The Netherlands.

Funding for this research comes in part from the UCSD Christini Fund, the Wright Family Foundation, the Lennox Foundation and the UCSD Mitochondrial Disease Research Fund.


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