Dataset Information

Metabolomic differences in heart failure patients with and without major depression.

ABSTRACT: Metabolomics is an emerging technology that allows researchers to characterize hundreds of small molecules that comprise the metabolome. We sought to determine metabolic differences in depressed and nondepressed participants. The sample consisted of a depressed group of patients with heart failure enrolled in an NIMH-supported clinical trial of sertraline versus placebo in depressed heart failure patients, and a nondepressed comparator group of heart failure patients. Plasma was obtained from blood samples provided by participants at baseline, and samples were profiled on GC-MS and LC-MS metabolomics platforms for biochemical content. A number of biochemicals were significantly different between groups, with depressed participants showing higher concentrations of several amino acids and dicarboxylic fatty acids. These results are consistent with prior findings where changes in neurotransmitter systems and fatty acid metabolism were shown to associate with the depressed state. It is unclear what role heart failure may have played in these differing concentrations.

SUBMITTER: Steffens DC

PROVIDER: S-EPMC3279728 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolomic differences in heart failure patients with and without major depression.

Steffens David C DC Wei Jiang Krishnan K Ranga R KR Karoly Edward D ED Mitchell Matthew W MW O'Connor Christopher M CM Kaddurah-Daouk Rima R

Journal of geriatric psychiatry and neurology 20100125 2

Metabolomics is an emerging technology that allows researchers to characterize hundreds of small molecules that comprise the metabolome. We sought to determine metabolic differences in depressed and nondepressed participants. The sample consisted of a depressed group of patients with heart failure enrolled in an NIMH-supported clinical trial of sertraline versus placebo in depressed heart failure patients, and a nondepressed comparator group of heart failure patients. Plasma was obtained from bl ...[more]

PMID: 20101071

Similar Datasets

Project description:BACKGROUND: In patients with chronic heart failure, depression is common and associated with poor quality of life, more frequent hospitalizations, and higher mortality. Spiritual well-being is an important, modifiable coping resource in patients with terminal cancer and is associated with less depression, but little is known about the role of spiritual well-being in patients with heart failure. OBJECTIVE: To identify the relationship between spiritual well-being and depression in patients with heart failure. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty patients aged 60 years or older with New York Heart Association class II-IV heart failure. MEASUREMENTS: Spiritual well-being was measured using the total scale and 2 subscales (meaning/peace, faith) of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being scale, depression using the Geriatric Depression Scale-Short Form (GDS-SF). RESULTS: The median age of participants was 75 years. Nineteen participants (32%) had clinically significant depression (GDS-SF > 4). Greater spiritual well-being was strongly inversely correlated with depression (Spearman's correlation -0.55, 95% confidence interval -0.70 to -0.35). In particular, greater meaning/peace was strongly associated with less depression (r = -.60, P < .0001), while faith was only modestly associated (r = -.38, P < .01). In a regression analysis accounting for gender, income, and other risk factors for depression (social support, physical symptoms, and health status), greater spiritual well-being continued to be significantly associated with less depression (P = .05). Between the 2 spiritual well-being subscales, only meaning/peace contributed significantly to this effect (P = .02) and accounted for 7% of the variance in depression. CONCLUSIONS: Among outpatients with heart failure, greater spiritual well-being, particularly meaning/peace, was strongly associated with less depression. Enhancement of patients' sense of spiritual well-being might reduce or prevent depression and thus improve quality of life and other outcomes in this population.

Project description:The failing heart is characterized by elevated levels of reactive oxygen species. We have developed an animal model of heart failure induced by chemogenetic production of oxidative stress in the heart using a recombinant adeno-associated virus (AAV9) expressing yeast d-amino acid oxidase (DAAO) targeted to cardiac myocytes. When DAAO-infected animals are fed the DAAO substrate d-alanine, the enzyme generates hydrogen peroxide (H2O2) in the cardiac myocytes, leading to dilated cardiomyopathy. However, the underlying mechanisms of oxidative stress-induced heart failure remain incompletely understood. Therefore, we investigated the effects of chronic oxidative stress on the cardiac transcriptome and metabolome. Rats infected with recombinant cardiotropic AAV9 expressing DAAO or control AAV9 were treated for 7 wk with d-alanine to stimulate chemogenetic H2O2 production by DAAO and generate dilated cardiomyopathy. After hemodynamic assessment, left and right ventricular tissues were processed for RNA sequencing and metabolomic profiling. DAAO-induced dilated cardiomyopathy was characterized by marked changes in the cardiac transcriptome and metabolome both in the left and right ventricle. Downregulated transcripts are related to energy metabolism and mitochondrial function, accompanied by striking alterations in metabolites involved in cardiac energetics, redox homeostasis, and amino acid metabolism. Upregulated transcripts are involved in cytoskeletal organization and extracellular matrix. Finally, we noted increased metabolite levels of antioxidants glutathione and ascorbate. These findings provide evidence that chemogenetic generation of oxidative stress leads to a robust heart failure model with distinct transcriptomic and metabolomic signatures and set the basis for understanding the underlying pathophysiology of chronic oxidative stress in the heart.NEW & NOTEWORTHY We have developed a "chemogenetic" heart failure animal model that recapitulates a central feature of human heart failure: increased cardiac redox stress. We used a recombinant DAAO enzyme to generate H2O2 in cardiomyocytes, leading to cardiomyopathy. Here we report striking changes in the cardiac metabolome and transcriptome following chemogenetic heart failure, similar to changes observed in human heart failure. Our findings help validate chemogenetic approaches for the discovery of novel therapeutic targets in heart failure.

Dataset Information

Metabolomic differences in heart failure patients with and without major depression.

Publications

Metabolomic differences in heart failure patients with and without major depression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets