Branched-Chain Amino Acids as New Biomarkers of Major Depression - A Novel Neurobiology of Mood Disorder

The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are...

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Vydáno v:	PloS one Ročník 11; číslo 8; s. e0160542
Hlavní autoři:	Baranyi, Andreas, Amouzadeh-Ghadikolai, Omid, von Lewinski, Dirk, Rothenhäusler, Hans-Bernd, Theokas, Simon, Robier, Christoph, Mangge, Harald, Reicht, Gerhard, Hlade, Peter, Meinitzer, Andreas
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 04.08.2016 Public Library of Science (PLoS)
Témata:	Activation Adult Amino acids Amino Acids, Branched-Chain - analysis Antidepressants Biology and Life Sciences Biomarkers Biomarkers - analysis Branched chain amino acids Case-Control Studies Cell growth Chain branching Chains Chromatography Chromatography, High Pressure Liquid Correlation Correlation coefficient Correlation coefficients Depressive Disorder, Major - diagnosis Depressive Disorder, Major - metabolism Depressive Disorder, Major - pathology Diagnosis Disease Down-Regulation Electrical impedance Energy Metabolism Etiology Female Gene expression Health aspects High-performance liquid chromatography Hospitals Humans Identification and classification Isoleucine Isoleucine - chemistry Isoleucine - metabolism Kinases Laboratories Leucine Leucine - chemistry Leucine - metabolism Liquid chromatography Major depressive disorder Male Mammals Medicine Medicine and Health Sciences Mental depression Metabolism Metabolites Middle Aged Mood Mood Disorders - metabolism Mood Disorders - pathology Mortality Nervous system Nervous System - metabolism Neurosciences Patients Phosphorylation Physical Sciences Physiological aspects Protein synthesis Proteins Psychiatry Psychotherapy Rapamycin Research projects Signal transduction Signaling Stroke TOR protein TOR Serine-Threonine Kinases - metabolism Valine Valine - chemistry Valine - metabolism Austria
ISSN:	1932-6203, 1932-6203
On-line přístup:	Získat plný text
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Popis
Shrnutí:	The proteinogenic branched-chain amino acids (BCAAs) valine, leucine and isoleucine might play an unrecognised crucial role in the development of depression through their activation of the mammalian target of rapamycin (mTor) pathway. The aim of this research project is to evaluate whether BCAAs are altered in patients with major depression and might thus be appropriate biomarkers for major depression. The concentrations of valine, leucine and isoleucine were determined in 71 in-patients with major depression and 48 healthy controls by high-pressure liquid chromatography. Psychiatric and laboratory assessments were obtained at the time of in-patient admittance. The BCAAs are significantly decreased in patients with major depression in comparison with healthy subjects (valine: Mann-Whitney-U: 968.0; p <0.0001, leucine: Mann-Whitney-U: 1246.5; p = 0.013, isoleucine: Mann-Whitney-U: 1252.5; p = 0.014). Furthermore, as shown by Spearman's rank correlation coefficients, there is a significant negative correlation between valine, leucine and isoleucine concentrations and the Hamilton Depression Rating Scale (HAMD-17) as well as Beck Depression Inventory (BDI-II) scores. Our study results are strong evidence that in patients with major depression, BCAAs might be appropriate biomarkers for depression. Reduced activation of the mammalian target of rapamycin (mTor) due to a reduction of BCAAs might play a crucial unrecognised factor in the etiology of depression and may evoke depressive symptomatology and lower energy metabolism in patients with major depression. In the future, mTor and its up- and downstream signalling partners might be important targets for the development of novel antidepressants.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: AB OAG AM DvL.Performed the experiments: AB OAG DvL HBR ST CR GH PH HM AM.Analyzed the data: AB OAG DvL HBR ST CR GH PH HM AM.Contributed reagents/materials/analysis tools: AM AB CR HM GR PH.Wrote the paper: AB OAG DvL HBR ST CR GH PH HM AM. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0160542