summary: Researchers have found an important link between cellular metabolism and major depressive disorder, particularly in treatment-resistant cases and suicidal ideation. This study found specific blood metabolites that are different in depressed patients, providing new biomarkers for risk assessment.
The study also highlights gender differences in the metabolic effects of depression and suggests that mitochondrial dysfunction is involved in suicidal ideation. These insights provide new avenues for personalized treatment and prevention strategies, with the potential to leverage supplements such as folic acid and carnitine to address metabolic gaps.
Important facts:
- Researchers have identified certain metabolites in the blood as biomarkers for depression and suicide risk.
- This study reveals gender differences in metabolic effects and focuses on mitochondrial dysfunction in suicidal ideation.
- The findings suggest the potential for personalized treatment using metabolic supplements for depression.
sauce: UCSD
Major depressive disorder affects 16.1 million adults in the United States and costs $210 billion annually. Although the main symptoms of depression are psychological, scientists and doctors have come to understand that depression is a complex disease that physically affects the entire body.
For example, measuring markers of cellular metabolism has become an important approach to studying mental illnesses and developing new ways to diagnose, treat, and prevent them.
Researchers at the University of California, San Diego School of Medicine have now advanced this field in a new study, uncovering a link between cellular metabolism and depression.
Researchers have found that depressed and suicidal people have detectable compounds in their blood that can help identify those at high risk of suicide. The researchers also found that there are gender-based differences in how depression affects cellular metabolism.
The findings were published on December 15, 2023. translational psychiatrycould help personalize mental health care and identify new targets for future medicines.
“Mental illnesses such as depression have impacts and drivers far beyond the brain,” said Robert Navio, MD, professor in the Department of Medicine, Pediatrics, and Pathology at the University of California, San Diego School of Medicine.
“Until about 10 years ago, it was difficult to study how systemic chemical reactions affected our behavior and mental state. But thanks to modern techniques such as metabolomics, we are now able to I can now listen to conversations in my native language, biochemistry.”
Although many people with depression experience improvement with psychotherapy and drug therapy, some people with depression are treatment resistant and have little or no effect on treatment. Suicidal ideation is experienced by a large proportion of people with treatment-resistant depression, and up to 30% of people will attempt suicide at least once in their lifetime.
“Mid-life mortality rates are increasing significantly in the United States, and increasing suicide rates are one of many factors driving that trend,” Navio said. “A tool that helps stratify people based on suicide risk could help save lives.”
Researchers analyzed the blood of 99 study participants with treatment-resistant depression and suicidal ideation, as well as an equal number of healthy controls.
They found that of the hundreds of different biochemicals circulating in the blood of these people, five could be used as biomarkers to classify patients with treatment-resistant depression and suicidal ideation. discovered. However, which five can be used differs between men and women.
“If you have 100 people who don't have depression, or who have depression and suicidal thoughts, who is most at risk based on five metabolites in men and another five in women? We will be able to pinpoint 85 to 90 of them,” Navio said.
“While this may be important from a diagnostic perspective, it also opens up a broader discussion in the field about what is actually causing these metabolic changes.”
Although there were clear differences in blood metabolism between men and women, some metabolic markers of suicidal ideation were consistent between men and women. This included biomarkers for mitochondrial dysfunction, which occurs when a cell's energy-producing structures malfunction.
“Mitochondria are some of the most important structures in our cells, and alterations in mitochondrial function occur in many human diseases,” Naviaux added.
Mitochondria produce ATP, the main energy currency for all cells. ATP is also an important molecule for communication between cells, and researchers hypothesize that it is this function that is most dysregulated in people with suicidal thoughts.
“When inside the cell, ATP 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,” Naviaux said.
“We hypothesize that suicide attempts may actually be part of a larger physiological drive to shut down a stress response that has become intolerable at the cellular level.”
Some of the metabolic deficiencies identified in this study were found in compounds available as supplements, such as folic acid and carnitine, so the researchers used these compounds to treat depression in order to fill in the metabolic deficiencies. I am interested in exploring the possibility of personalizing disease treatment. Necessary for recovery. Naviaux adds that these supplements are not a cure.
“None of these metabolites are magic bullets that will completely reverse depression,” Navio says.
“However, our results show that there may be things that can be done to steer metabolism in the right direction to make patients more responsive to treatment, and in the context of suicide, it may be possible for people to do that. This may be enough to prevent the threshold from being exceeded.”
In addition to suggesting new approaches to personalizing treatments for depression, this study could help scientists discover new drugs that can target mitochondrial dysfunction, which could have implications for overall human health. could have far-reaching effects.
“Many chronic illnesses co-exist with depression because dealing with an illness for years at a time can be extremely stressful,” Navio says.
“If we can find ways to treat depression and suicidal ideation at a metabolic level, we may also be able to help improve outcomes for many of the diseases that lead to depression.
“Many chronic diseases, such as post-traumatic stress disorder and chronic fatigue syndrome, are not fatal in themselves unless they lead to suicidal thoughts or behavior. We can use metabolomics to identify those most at risk. If we can identify that, we could ultimately save more lives.”
Co-authors include Jane C. Naviaux, Lin Wang, Kefeng Li, Jonathan M. Monk and Sai Sachin Lingampelly of the University of California, San Diego, Lisa A. Pan, Anna Maria Segreti, Kaitlyn Bloom, Jerry Vockley, David N. Finegold; Includes David. G. Peters of the University of Pittsburgh School of Medicine and Mark A. Tarnopolsky of McMaster University.
About this depression research news
author: Miles Martin
sauce: UCSD
contact: Miles Martin – UCSD
image: Image credited to Neuroscience News
Original research: Open access.
“Metabolic features of treatment-resistant major depressive disorder with suicidal ideation” by Robert Navio et al. translational psychiatry
abstract
Metabolic features of treatment-resistant major depressive disorder with suicidal ideation
Peripheral blood metabolomics has been used to gain chemical insight into the biology of treatment-resistant major depressive disorder with suicidal ideation and to identify individual differences for personalized care. Ta.
The study cohort consisted of 99 patients with treatment-resistant major depressive disorder and suicidal ideation (trMDD-SI). n= 52 women, 47 men) and 94 age- and sex-matched healthy controls (n= 48 women, 46 men). Median age was 29 years (IQR 22-42). Targeted broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction.
The diagnostic accuracy of plasma metabolomics was >90% (95%CI: 0.80 to 1.0) by area under receiver operating characteristic (AUROC) curve analysis. More than 55% of the metabolic effects in men and 75% in women were due to lipid abnormalities.
Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both men and women. Increases in lactate, glutamate, and saccharopine and decreases in cystine provided evidence of stress reduction. Seventy-five percent of the metabolic abnormalities found were individual.
Personal deficiencies of CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folic acid were found. Pathways regulated by mitochondrial function dominated the metabolic signature.
Peripheral blood metabolomics identifies mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-resistant major depressive disorder.
Differences in individual metabolism have been discovered, which may help in individual management.
