A metabolomic study of cervical dystonia

Liu, Chang; Scorr, Laura; Kilic‐Berkmen, Gamze; Cotton, Adam; Factor, Stewart A.; Freeman, Alan; Tran, ViLinh; Liu, Ken; Uppal, Karan; Jones, Dean P.; Jinnah, Hyder A.; Sun, Yan V.

doi:10.1016/j.parkreldis.2020.11.020

Cited by 8 publications

(6 citation statements)

References 30 publications

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“…Another recent metabolomic study by Liu et al shows interesting differences in specific metabolites between controls and CD patients [34]. However, monoamines and amino acids were not reported and therefore it is difficult to compare the results observed in our study and theirs.…”

Section: This Figure Shows the Correlations Between The Non-motor Symptoms And Concentrations Of Metabolites In The Dystonia Group (Excl contrasting

confidence: 78%

Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

Timmers

Faassen

Smit

et al. 2021

Parkinsonism & Related Disorders

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In dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations. Methods: Concentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites. Results: A significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (r s = − 0.3, p < 0.01), depression (r s = − 0.3, p < 0.01) and fatigue (r s = − 0.2, p = 0.04). Conclusion:This study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.

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Section: This Figure Shows the Correlations Between The Non-motor Symptoms And Concentrations Of Metabolites In The Dystonia Group (Excl contrasting

confidence: 78%

Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

Timmers

Faassen

Smit

et al. 2021

Parkinsonism & Related Disorders

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“…In addition, metabolomics has a particular advantage over other technologies including genomics, transcriptomics, and proteomics in that it could provide a global phenotype of metabolic changes. This approach is now being utilized to find evidence of major changes in metabolites such as amino acids, lipids, and neurotransmitters in dystonia-related diseases [ 11 – 13 ]. There have been no reports of using metabolomics to uncover pathogenic aspects or diagnostic biomarkers in BEB patients, suggesting that this novel technology must be employed to identify probable biomarkers of BEB as well as explore the disease's pathogenesis and treatment approaches.…”

Section: Introductionmentioning

confidence: 99%

Serum Metabolomics of Benign Essential Blepharospasm Using Liquid Chromatography and Orbitrap Mass Spectrometry

Zhao

Wang

Lin

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Benign essential blepharospasm (BEB) is a form of focal dystonia that causes excessive involuntary spasms of the eyelids. Currently, the pathogenesis of BEB remains unclear. This study is aimed at investigating the serum metabolites profiles in patients with BEB and healthy control and to identify the mechanism and biomarkers of this disease. Methods. 30 patients with BEB and 33 healthy controls were recruited for this study. We conducted the quantitative and nontargeted metabolomics analysis of the serum samples from 63 subjects by using liquid chromatography and Orbitrap mass spectrometry (LC-Orbitrap MS). Multivariate statistical analysis was performed to detect and identify different metabolites between the two groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and receiver operating characteristic (ROC) curve analysis of the altered metabolites were performed. Results. A total of 134 metabolites were found and identified. The metabolites belonged to several metabolic pathways including phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, linoleic acid metabolism, tryptophan metabolism, aminoacyl-tRNA biosynthesis, sphingolipid metabolism, glycosphingolipid biosynthesis, leucine and isoleucine biosynthesis, and vitamin B6 metabolism. Eight metabolites were identified as the potential biomarkers. Conclusions. These results demonstrated that serum metabolic profiling of BEB patients was significantly different from healthy controls based on LC-Orbitrap MS. Besides, metabolomics might provide useful information for a better understanding of BEB.

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“…In 2020, the Biobank added collection of RNA and plasma that will allow for additional studies including transcriptomics, proteomics or lipidomics, epigenomics, and others. A pilot study of metabolomics has provided hints that this approach may be successful (64). The goal is to create a resource for biomarker discovery and validation.…”

Section: Biobank Projectmentioning

confidence: 99%

The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies

et al. 2021

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Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia.

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A metabolomic study of cervical dystonia

Cited by 8 publications

References 30 publications

Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

Serum Metabolomics of Benign Essential Blepharospasm Using Liquid Chromatography and Orbitrap Mass Spectrometry

The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies

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