In a finding that could have a significant impact on personalized medicine and treatment, scientists have identified blood compounds linked to suicidal ideation.
University of California (UC) San Diego researchers have found biomarkers linked to mitochondrial dysfunction, which interrupts how cells ‘talk’ to each other and could be a factor in suicidal ideation. While suicide is complex and includes broad factors such as trauma and stress, being able to identify those most at risk could be a crucial diagnostic tool.
“Mental illnesses like depression have impacts and drivers well beyond the brain,” said Robert Naviaux, a professor at UC San Diego. “Prior to about 10 years ago it was difficult to study how the chemistry of the whole body influences our behavior and state of mind, but modern technologies like metabolomics are helping us listen in on cells’ conversations in their native tongue, which is biochemistry.”
Earlier this year, scientists discovered molecular links to suicidal ideation, showing that some people who suffer from depression could be more at risk. And research into blood markers has been under way since 2019.
In this study, the researchers analyzed the blood of 99 adults with depression and suicidal ideation that traditional treatments had not helped, as well as 99 ‘healthy’ participants with no history of mental illness. While hundreds of different biochemicals were found in the blood of the focus cohort, five specific ones were identified as key factors to treatment-resistant depression and suicidal ideation.
The metabolomics identified, which contribute to a breakdown in intercellular communication, stem from the mitochondria. Known as the powerhouses of cells, mitochondria facilitate production of ATP energy, which is essential for fueling the body. The five biochemicals, which were consistent among men and women, appear to change this process in a cohort of those with depression.
“Mitochondria are some of the most important structures of our cells and changed mitochondrial functions occur in a host of human diseases,” said Naviaux. “When ATP is inside the cell it acts like an energy source, but outside the cell it is a danger signal that activates dozens of protective pathways in response to some environmental stressor. We hypothesize that suicide attempts may actually be part of a larger physiological impulse to stop a stress response that has become unbearable at the cellular level.”
Now, the researchers hope that these findings can lead to more personalized mental health treatment and a target for drugs that may help those who have not responded to current clinical care.
“If we have 100 people who either don’t have depression or who have depression and suicidal ideation, we would be able to correctly identify 85-90 of those at greatest risk based on five metabolites in males and another five metabolites in females,” said Naviaux. “This could be important in terms of diagnostics, but it also opens up a broader conversation in the field about what’s actually leading to these metabolic changes.”
Among the metabolites identified, some currently exist in supplements such as folate and carnitine. This has also provided the researchers with an exciting new avenue of study.
“None of these metabolites are a magic bullet that will completely reverse somebody’s depression,” said Naviaux. “However, our results tell us that there may be things we can do to nudge the metabolism in the right direction to help patients respond better to treatment, and in the context of suicide, this could be just enough to prevent people from crossing that threshold.”
The study was published in the journal Translational Medicine.
