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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div

Additional file 1 of Alterations in trimethylamine-N-oxide in response to Empagliflozin therapy: a secondary analysis of the EMMY trial

Additional file 1: Fig. S1. Distribution of untransformed TMAO concentration (μmol/L) by treatment groups at A—baseline, B—6 weeks, and C—26 weeks. Table S1. LDL-C levels over visits by treatment groups

Spearman's rank correlation coefficients between branched-chain amino acids and Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI-II) scores.

<p>Spearman's rank correlation coefficients between branched-chain amino acids and Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI-II) scores.</p

Biological assessments for the patients with major depression at the time of in-patient admittance to the Department of Psychiatry and healthy controls.

<p>Biological assessments for the patients with major depression at the time of in-patient admittance to the Department of Psychiatry and healthy controls.</p

HAMD-17 and BDI-II scores for the patients with major depression and healthy controls [14].

<p>HAMD-17 and BDI-II scores for the patients with major depression and healthy controls [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160542#pone.0160542.ref014" target="_blank">14</a>].</p

Sociodemographic and clinical characteristics of the participants [14].

<p>Sociodemographic and clinical characteristics of the participants [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0160542#pone.0160542.ref014" target="_blank">14</a>].</p

MOESM2 of Impaired aspirin-mediated platelet function inhibition in resuscitated patients with acute myocardial infarction treated with therapeutic hypothermia: a prospective, observational, non-randomized single-centre study

Additional file 2. Demographic data within the group of resuscitated patients divided by the P2Y12 inhibitor used

MOESM1 of Impaired aspirin-mediated platelet function inhibition in resuscitated patients with acute myocardial infarction treated with therapeutic hypothermia: a prospective, observational, non-randomized single-centre study

Additional file 1. Association of platelet function and SOFA score

Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity

BackgroundHeart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction.MethodsWe randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level.ResultsThe mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; PConclusionsIn patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. (Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.)