PMID- 27490818
OWN - NLM
STAT- MEDLINE
DCOM- 20170823
LR  - 20220321
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 8
DP  - 2016
TI  - Branched-Chain Amino Acids as New Biomarkers of Major Depression - A Novel 
      Neurobiology of Mood Disorder.
PG  - e0160542
LID - 10.1371/journal.pone.0160542 [doi]
LID - e0160542
AB  - 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.
FAU - Baranyi, Andreas
AU  - Baranyi A
AD  - Department of Psychiatry and Psychotherapeutic Medicine, Medical University of 
      Graz, Graz, Austria.
AD  - Institute for International Management Practice, ARU Cambridge, Cambridge, UK.
FAU - Amouzadeh-Ghadikolai, Omid
AU  - Amouzadeh-Ghadikolai O
AD  - Hospital of the Brothers of St. John of God, Graz, Austria.
FAU - von Lewinski, Dirk
AU  - von Lewinski D
AD  - Division of Cardiology, Department of Internal Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Rothenhausler, Hans-Bernd
AU  - Rothenhausler HB
AD  - Department of Psychiatry and Psychotherapeutic Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Theokas, Simon
AU  - Theokas S
AD  - Department of Psychiatry and Psychotherapeutic Medicine, Medical University of 
      Graz, Graz, Austria.
FAU - Robier, Christoph
AU  - Robier C
AD  - Hospital of the Brothers of St. John of God, Graz, Austria.
AD  - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical 
      University of Graz, Graz, Austria.
FAU - Mangge, Harald
AU  - Mangge H
AD  - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical 
      University of Graz, Graz, Austria.
FAU - Reicht, Gerhard
AU  - Reicht G
AD  - Hospital of the Brothers of St. John of God, Graz, Austria.
FAU - Hlade, Peter
AU  - Hlade P
AD  - Hospital of the Brothers of St. John of God, Graz, Austria.
FAU - Meinitzer, Andreas
AU  - Meinitzer A
AD  - Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical 
      University of Graz, Graz, Austria.
LA  - eng
PT  - Journal Article
DEP - 20160804
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Biomarkers)
RN  - 04Y7590D77 (Isoleucine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GMW67QNF9C (Leucine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Adult
MH  - Amino Acids, Branched-Chain/*analysis
MH  - Biomarkers/*analysis
MH  - Case-Control Studies
MH  - Chromatography, High Pressure Liquid
MH  - Depressive Disorder, Major/*diagnosis/metabolism/pathology
MH  - Down-Regulation
MH  - Energy Metabolism
MH  - Female
MH  - Humans
MH  - Isoleucine/chemistry/metabolism
MH  - Leucine/chemistry/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mood Disorders/metabolism/pathology
MH  - Nervous System/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Valine/chemistry/metabolism
PMC - PMC4973973
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/08/05 06:00
MHDA- 2017/08/24 06:00
PMCR- 2016/08/04
CRDT- 2016/08/05 06:00
PHST- 2016/04/27 00:00 [received]
PHST- 2016/07/21 00:00 [accepted]
PHST- 2016/08/05 06:00 [entrez]
PHST- 2016/08/05 06:00 [pubmed]
PHST- 2017/08/24 06:00 [medline]
PHST- 2016/08/04 00:00 [pmc-release]
AID - PONE-D-16-15750 [pii]
AID - 10.1371/journal.pone.0160542 [doi]
PST - epublish
SO  - PLoS One. 2016 Aug 4;11(8):e0160542. doi: 10.1371/journal.pone.0160542. 
      eCollection 2016.