People with suicidal ideation found markers of mitochondrial dysfunction in blood
American doctors analyzed the blood metabolomics of 99 patients with major depressive disorder and suicidal ideation and found that they had elevated levels of fibroblast growth factor 21 and growth differentiation factor 15 - markers of mitochondrial dysfunction. As reported in the journal Translational Psychiatry, overall, most patients showed individual changes in metabolomics, which can be used for personalized treatment.
There is a trend of increasing mortality in middle-aged people around the world. In the US in particular, this trend has been attributed to an increase in suicides and drug overdoses - "deaths of despair". However, suicides among adolescents and young adults are also on the rise. Although psychopharmacotherapy can effectively manage the symptoms of major depressive disorder, in which patients often have suicidal thoughts and intentions, there are cases of treatment-resistant depressive disorder.
The growing understanding that the brain modulates metabolism through neuroendocrine, autonomic, immune, and microbiome circuits provides scientific rationale for using peripheral blood metabolomics to discover novel biomarkers of various diseases, including psychiatric diseases. Previous studies have shown that plasma metabolomics can be used as a diagnostic tool in the study of chronic fatigue syndrome and schizophrenia.
Robert Naviaux of UCLA assembled a team of scientists to characterize the plasma metabolome of blood from patients with treatment-resistant severe depression and suicidal ideation. To do so, they analyzed the metabolome of 99 men and women with this disorder and 93 healthy controls. The average age of the patients was 29 years. Most patients had a history of major depressive disorder, and additional psychiatric diagnoses were often made. Generalized anxiety disorder occurred in 70-75 percent of patients, and bipolar disorder in 30-35 percent.
Multivariate analysis showed that patients with treatment-refractory major depressive disorder differed significantly from healthy control participants. Men had a greater decrease in plasmalogens associated with peroxisomal metabolism, while women had a greater increase in signaling eicosanoids such as 5-hydroxeicosatetraenoic acid.
Researchers identified fibroblast growth factor 21 and growth differentiation factor 15 as biomarkers of mitochondrial dysfunction and mitochondrial integrated stress response. Fibroblast growth factor 21 levels were elevated in both men and women in the study group; women also had elevated levels of growth differentiation factor 15. Additional analysis showed that the levels of these factors were positively correlated with the lipid metabolites 7-dehydrocholesterol and several phospholipids.
In addition, participants in the study group were found to have increased levels of lactate, glutamate, saccharopin, gamma-glutamylalanine, and decreased levels of cystine. Such changes are indicative of impaired mitochondrial oxidation. Elevated levels of modified purines - 1-methyladenosine and 7-methylguanine - were also observed in patients.
In addition, almost every patient had individualized changes in metabolomics. According to the authors of the paper, this suggests the potential for a personalized approach in the diagnosis and treatment of major depressive disorder. However, it is first necessary to determine to what extent mitochondrial dysfunction affects the severity of the disease.