Identification of Gender-Specific Metabolic Markers in Blood for Suicidal Thoughts in Treatment-Resistant Depression: A UC San Diego Study

It has been a long-standing goal to develop a blood detection test for suicidal thoughts or ideation. This team of biologists and psychiatrists from the University of California in San Diego is nearing this goal by identifying reliable metabolic markers of suicidal thoughts. Some of these biomarkers also reveal the presence of mitochondrial dysfunction.

Mitochondria

Mitochondria

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Major depressive disorder affects 280 million people worldwide. Although its main symptoms are psychological, depression is a complex disease that also causes physical effects throughout the body. Thus, measuring certain markers of cellular metabolism emerges as a promising new approach to studying mental illnesses and developing new ways to diagnose, treat, and prevent them.

A link between cellular metabolism and depression.

The research reveals that people suffering from depression and suicidal thoughts have specific compounds detectable in their blood that could identify this suicide risk. Gender differences are observed in the impact of depression on cellular metabolism. This new diagnostic method, therefore, involves the mitochondria. The disruption of mitochondrial networks or cellular metabolism seems associated with suicidal thoughts.

“Mental illnesses like depression have impacts and factors far beyond the brain,” explains one of the main authors, Dr. Robert Naviaux, professor of medicine, pediatrics, and pathology at UC San Diego. “About ten years ago, it was difficult to study how the chemistry of the entire body influences our behavior and mood, metabolomics helps us understand these processes at the cellular level today.”

Depression has its complications, with about a third of patients resistant to available treatments, including psychotherapy and antidepressants, and some of them experiencing suicidal thoughts. Among these patients suffering from treatment-resistant depression, up to 30% will make at least one suicide attempt in their lifetime.

With the increasing prevalence of depression worldwide, the incidence of suicide also increases. Therefore, it is urgent to have tools that allow grouping patients with depression according to their risk of suicidal ideation.

The study analyzed the blood of 99 participants suffering from treatment-resistant depression and diagnosed with suicidal tendencies, as well as an equal number of healthy people.

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Gender Differences in Depression’s Metabolic Impact

5 compounds found in the blood of depressed patients were identified as markers of suicidal thoughts. However, these 5 markers do not have the same meaning for men and women. In general, 5 metabolites would correctly identify 85-90% of the most at-risk people, in men, and 5 other metabolites in women. These results are explained by differences in blood metabolism between men and women, with some metabolic markers of suicidal ideas being consistent across both sexes. Among these metabolites are markers of mitochondrial dysfunction. Mitochondrial dysfunctions are observed in a multitude of human diseases, point out the authors.

Mitochondrial Dysfunction and Treatment Possibilities

Mitochondria produce ATP, the main energy source of cells. ATP is also an important molecule for cell-to-cell communication, and researchers hypothesize that this function is the most deregulated in people with suicidal ideas. When ATP is inside the cell, it acts as an energy source, but outside the cell, it is a danger signal that activates dozens of protective pathways in response to a stress factor. The researchers hypothesize that suicide attempts could be part of a broader physiological impulse aimed at ending a stress response that has become unbearable at the cellular level. Given that some of the metabolic deficiencies identified in the study were compounds available in supplement form, such as folate and carnitine, researchers want to explore the possibility of individualizing the treatment of depression with these compounds to help recalibrate metabolism. And if these supplements could not completely reverse depression, could they help the metabolism get back on the right track and thus reduce the risk of suicide?

A New Approach to Treating Depression

This discovery, therefore, encourages testing drugs capable of targeting mitochondrial dysfunction, with vast implications for human health in general. “If we can find ways to treat depression and suicidal thoughts at the metabolic level, we will also be able to improve the management of many diseases that lead to depression. If metabolomics proves effective in identifying the most at-risk patients, it will also help us personalize treatments and many mental health care services.”

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Final Thoughts

It’s important to maintain a balanced perspective on these findings. Mental health complexities and individual differences mean that this approach while promising, is not a one-size-fits-all solution. The study’s emphasis on treatment-resistant depression also raises questions about its applicability to all depression cases. Looking ahead, the potential of personalized treatments based on metabolic dysfunctions offers a hopeful avenue, yet it’s crucial to proceed with careful, ongoing research to fully understand its implications and effectiveness.

References

Pan, L.A., Naviaux, J.C., Wang, L. et al. Metabolic features of treatment-refractory major depressive disorder with suicidal ideation. Transl Psychiatry 13, 393 (2023). https://doi.org/10.1038/s41398-023-02696-9

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