Telltales of depression in our blood
Depression is a major cause of disability worldwide. Due to its complex nature, it is difficult to explain the molecular pathways associated with depression by examining the genetic factors. e:Med junior research alliance CKDNapp chose a metabolomics approach to tackle this problem. The results of their population-wide screen for metabolites revealed laurylcarnitine to be associated with depression. This metabolite is involved in the fatty acid oxidation pathway and may provide new therapy options against depression.
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The scientists of CKDNapp, led by Professor Helena Zacharias (UKSH, Kiel) focussed on examination of metabolites, i.e., small molecules, in blood samples in order to trace back to the relevant pathways. They analyzed 353 metabolites in blood samples of a cohort of 1411 people (KORA cohort—Cooperative Health Research in the Augsburg Region). Incorporated was information about their sex, age, body mass index (BMI), and intake of relevant drugs (antidiabetics, antihypertensive drugs, thyroid gland hormone drugs, anti-inflammatory and anti-rheumatic drugs, as well as anti-depressants). Depressed mood was determined by a patient questionnaire. The researchers comprehensively examined the blood of the subjects for metabolites, such as amino acids, carbohydrates, vitamins and cofactors, lipids, peptides, as well as metabolites involved in energy metabolism. Surprisingly, it was only laurylcarnitine that showed a consistent and moreover negative association with depressed mood. The lower the levels, the more depressed people were. This suggests that laurylcarnitine levels affect depression and moreover the severity of this disorder. The statistical analysis showed the same relationship between lauryl-carnitine levels and depression, even when the population was stratified for sex, antidepressant use, and suicidal thoughts. To critically examine this result, the scientists measured the lauryl-carnitine levels in an independent replication cohort, and received consistent results here, too. Laurylcarnitine, which belongs to the chemical class of acylcarnitines, is involved in the fatty acid oxidation pathway. Acylcarnitines facilitate the transport of fatty acids from the cytosol into the mitochondria to create energy for the cells. Previous studies had shown that some antidepressants positively affect the energy metabolism of neurons in depressed people. This work suggests to exploit laurylcarnitine and the fatty acid oxidation pathway as novel therapeutic targets to fight depression disorders.
Original publication:
Zacharias, H. U., J. Hertel, H. Johar, M. Pietzner, K. Lukaschek, S. Atasoy, S. Kunze, H. Volzke, M. Nauck, N. Friedrich, G. Kastenmuller, H. J. Grabe, C. Gieger, J. Krumsiek and K. H. Ladwig (2021). "A metabolome-wide association study in the general population reveals decreased levels of serum laurylcarnitine in people with depression." Mol Psychiatry. https://doi.org/10.1038/s41380-021-01176-0.
Junior research alliance and contact person:
Prof. Dr. Helena Zacharias, (IKMB, Uni Kiel), h.zacharias@ikmb.uni-kiel.de
https://www.ikmb.uni-kiel.de/people/scientists/helena-zacharias