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

Baranyi, Andreas; Amouzadeh-Ghadikolai, Omid; Lewinski, Dirk von; Rothenhäusler, Hans-Bernd; Theokas, Simon; Robier, Christoph; Mangge, Harald; Reicht, G; Hlade, Peter; Meinitzer, Andreas

doi:10.1371/journal.pone.0160542

Cited by 89 publications

(79 citation statements)

References 35 publications

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“…Three main metabolite clusters are indicated colored in dark blue, light blue, and pink (see right side of the heatmap) chain amino acids (BCAAs) leucine, and isoleucine) and myo-inositol. BCAAs were recently proposed as biomarkers of depression and their observed profile in our study is in agreement with these reports 56 .…”

Section: Discussionsupporting

confidence: 94%

Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms

et al. 2019

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Antenatal depression affects~9-19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography-mass spectrometry (GC-MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts.

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Section: Discussionsupporting

confidence: 94%

Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms

et al. 2019

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“…have been previously implicated in MDD (Baranyi et al 2016) The lipid perturbations, especially those of the phosphatidylcholines (consisting of either 3 3 6 diacyl or alkyl-acyl moieties) showed positive correlations to the changes in HAM-D 17 scores. 3 3 7…”

mentioning

confidence: 84%

Pilot Study of Metabolomic Clusters as State Markers of Major Depression and Outcomes to CBT Treatment

Bhattacharyya

Dunlop²,

MahmoudianDehkordi

et al. 2019

Preprint

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1 Major depressive disorder (MDD) is a common and disabling syndrome with multiple 2 etiologies that is defined by clinically elicited signs and symptoms. In hopes of developing a list 3 of candidate biological measures that reflect and relate closely to the severity of depressive 4 symptoms, so-called "state-dependent" biomarkers of depression, this pilot study explored the 5 biochemical underpinnings of treatment response to cognitive behavior therapy (CBT) in 6 medication-freeMDD outpatients. Plasma samples were collected at baseline and week 12 from a 7 subset of MDD patients (N=26) who completed a course of CBT treatment as part of the 8Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) 9 study. Targeted metabolomic profiling using the the AbsoluteIDQ® p180 Kit and LC-MS 1 0identified eight "co-expressed" metabolomic modules. Of these eight, three were significantly 1 1 associated with change in depressive symptoms over the course of the 12-weeks. Metabolites 1 2found to be most strongly correlated with change in depressive symptoms were branched chain 1 3 amino acids, acylcarnitines, methionine sulfoxide, and α -aminoadipic acid (negative correlations 1 4with symptom change) as well as several lipids, particularly the phosphatidlylcholines (positive 1 5 correlation). These results implicate disturbed bioenergetics as an important state marker in the 1 6 pathobiology of MDD. Exploratory analyses contrasting remitters to CBT versus those who 1 7failed the treatment further suggest these metabolites may serve as mediators of recovery during 1 8CBT treatment. Larger studies examining metabolomic change patterns in patients treated with 1 9pharmacotherapy or psychotherapy will be necessary to elucidate the biological underpinnings of 2 0MDD and the -specific biologies of treatment response. 2 1

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“…This study is part of our research project on the ethiopathogenesis and health consequences of major depression. In former published studies ( Baranyi et al, 2015a ; Baranyi et al, 2016 ; Baranyi et al, 2017 ) of this research project we have investigated primarily the impact of beta-trace protein (BTP) as a new non-invasive immunological marker for QA-induced impaired blood-brain barrier integrity ( Baranyi et al, 2017 ). Later we have described the nitric oxide-related biological pathways ( Baranyi et al, 2015a ), and finally we have explored the impact of branched-chain amino acids (BCAAs) as new biomarkers of major depression ( Baranyi et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

“…In former published studies ( Baranyi et al, 2015a ; Baranyi et al, 2016 ; Baranyi et al, 2017 ) of this research project we have investigated primarily the impact of beta-trace protein (BTP) as a new non-invasive immunological marker for QA-induced impaired blood-brain barrier integrity ( Baranyi et al, 2017 ). Later we have described the nitric oxide-related biological pathways ( Baranyi et al, 2015a ), and finally we have explored the impact of branched-chain amino acids (BCAAs) as new biomarkers of major depression ( Baranyi et al, 2016 ). A total of 122 subjects (74 patients with major depression at the time of in-patient admittance to the Department of Psychiatry, Hospital of the Brothers of St. John of God, Graz, Austria, and 48 somatically healthy controls without current or former depression and without any former history of psychiatric disorders) were initially recruited for this ongoing research project.…”

Section: Methodsmentioning

confidence: 99%

Revisiting the tryptophan-serotonin deficiency and the inflammatory hypotheses of major depression in a biopsychosocial approach

Baranyi

Amouzadeh-Ghadikolai

Lewinski

et al. 2017

PeerJ

Self Cite

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BackgroundThe aim of this cross-sectional study was to identify important biopsychosocial correlates of major depression. Biological mechanisms, including the inflammatory and the tryptophan-serotonin deficiency hypotheses of major depression, were investigated alongside health-related quality of life, life satisfaction, and social support.MethodsThe concentrations of plasma tryptophan, plasma kynurenine, plasma kynurenic acid, serum quinolinic acid, and the tryptophan breakdown to kynurenine were determined alongside health-related quality of life (Medical Outcome Study Form, SF-36), life satisfaction (Life Satisfaction Questionnaire, FLZ), and social support (Social Support Survey, SSS) in 71 depressive patients at the time of their in-patient admittance and 48 healthy controls.ResultsCorresponding with the inflammatory hypothesis of major depression, our study results suggest a tryptophan breakdown to kynurenine in patients with major depression, and depressive patients had a lower concentration of neuroprotective kynurenic acid in comparison to the healthy controls (Mann–Whitney-U: 1315.0; p = 0.046). Contradicting the inflammatory theory, the concentrations of kynurenine (t: −0.945; df = 116; p = 0.347) and quinolinic acid (Mann-Whitney-U: 1376.5; p = 0.076) in depressive patients were not significantly different between depressed and healthy controls. Our findings tend to support the tryptophan-serotonin deficiency hypothesis of major depression, as the deficiency of the serotonin precursor tryptophan in depressive patients (t: −3.931; df = 116; p < 0.001) suggests dysfunction of serotonin neurotransmission. A two-step hierarchical linear regression model showed that low tryptophan concentrations, low social support (SSS), occupational requirements (FLZ), personality traits (FLZ), impaired physical role (SF-36), and impaired vitality (SF-36) predict higher Beck Depression Inventory (BDI-II) scores.DiscussionOur study results argue for the validity of a biopsychosocial model of major depression with multiple pathophysiological mechanisms involved.

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

Cited by 89 publications

References 35 publications

Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms

Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms

Pilot Study of Metabolomic Clusters as State Markers of Major Depression and Outcomes to CBT Treatment

Revisiting the tryptophan-serotonin deficiency and the inflammatory hypotheses of major depression in a biopsychosocial approach

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