title: Branched-Chain Amino Acids as New Biomarkers of Major Depression - A Novel Neurobiology of Mood Disorder.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.|Institute for International Management Practice, ARU Cambridge, Cambridge, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baranyi
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.
authors.forename: Omid
authors.initials: O
authors.lastname: Amouzadeh-Ghadikolai
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Dirk
authors.initials: D
authors.lastname: von Lewinski
authors.affiliation: Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Hans-Bernd
authors.initials: HB
authors.lastname: Rothenhäusler
authors.affiliation: Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Simon
authors.initials: S
authors.lastname: Theokas
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.|Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Robier
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Mangge
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Reicht
authors.affiliation: Hospital of the Brothers of St. John of God, Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Hlade
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
mesh_terms: D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000737:chemistry / Q000378:metabolism; D007930:Leucine / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000378:metabolism / Q000473:pathology; D009420:Nervous System / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014633:Valine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D015415:Biomarkers; D007532:Isoleucine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D014633:Valine