What Have Mass Spectrometry-Based Proteomics and Metabolomics (Not) Taught Us about Psychiatric Disorders?

Turck, Christoph W.; Filiou,

doi:10.1159/000381902

Cited by 15 publications

(11 citation statements)

References 79 publications

(92 reference statements)

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“…Multi-omics approaches have the potential to shed light on molecular mechanisms of psychiatric disorders in a high-throughput and data-driven manner (Filiou, 2015). Metabolomic analyses provide valuable information for dissecting neuropsychiatric conditions, as the metabolome correlates directly with the phenotype and is very sensitive to environmental stressors and changes (Quinones and Kaddurah-Daouk, 2009; Turck and Filiou, 2015). Metabolomic approaches have been used to study depression both in patient cohorts and animal models (Pan et al, 2018; Zhang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Serum Metabolomic Profile of Post-partum Depression

et al. 2019

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Post-partum depression (PPD) is a severe psychiatric disorder affecting ∼15% of young mothers. Early life stressful conditions in periconceptual, fetal and early infant periods or exposure to maternal psychiatric disorders, have been linked to adverse childhood outcomes interfering with physiological, cognitive and emotional development. The molecular mechanisms of PPD are not yet fully understood. Unraveling the molecular underpinnings of PPD will allow timely detection and establishment of effective therapeutic approaches. To investigate the underlying molecular correlates of PPD in peripheral material, we compared the serum metabolomes of an in detail characterized group of mothers suffering from PPD and a control group of mothers, all from Heraklion, Crete in Greece. Serum samples were analyzed by a mass spectrometry platform for targeted metabolomics, based on selected reaction monitoring (SRM), which measures the levels of up to 300 metabolites. In the PPD group, we observed increased levels of glutathione-disulfide, adenylosuccinate, and ATP, which associate with oxidative stress, nucleotide biosynthesis and energy production pathways. We also followed up the metabolomic findings in a validation cohort of PPD mothers and controls. To the very best of our knowledge, this is the first metabolomic serum analysis in PPD. Our data show that molecular changes related to PPD are detectable in peripheral material, thus paving the way for additional studies in order to shed light on the molecular correlates of PPD.

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Section: Discussionmentioning

confidence: 99%

Unraveling the Serum Metabolomic Profile of Post-partum Depression

et al. 2019

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“…Studies applying metabolomic profiling of patient serum are also starting to be used to explore the biology of psychiatric disorders [41,42,43,44,45,46]. Such studies have suggested the possibility of identifying biomarkers for schizophrenia [47,48,49,50,51,52], major depressive disorder [53,54] and posttraumatic stress disorder [55], and have also been used to study medication-induced metabolic changes [56,57].…”

Section: Discussionmentioning

confidence: 99%

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

et al. 2016

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Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder.

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“…In this review, neuropsychiatric disorders are restricted to anxiety, depression, bipolar disorder and schizophrenia which encompass most of the known symptoms in this group of diseases. Accurate diagnosis and treatment of these disorders is hindered by their etiological and clinical heterogeneity [116], hence the need for more reliable biomarkers as well as therapeutic interventions. Genomic studies have dominated neuropsychiatric research in the last decade and improved our understanding of mental diseases [117][118][119][120][121][122].…”

Section: Dynamics Of Processes In Neuropsychiatric Disordersmentioning

confidence: 99%

Recent advances in applying mass spectrometry and systems biology to determine brain dynamics

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Calza

Fuhrmann

et al. 2017

Expert Review of Proteomics

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Neurological disorders encompass various pathologies which disrupt normal brain physiology and function. Poor understanding of their underlying molecular mechanisms and their societal burden argues for the necessity of novel prevention strategies, early diagnostic techniques and alternative treatment options to reduce the scale of their expected increase. Areas covered: This review scrutinizes mass spectrometry based approaches used to investigate brain dynamics in various conditions, including neurodegenerative and neuropsychiatric disorders. Different proteomics workflows for isolation/enrichment of specific cell populations or brain regions, sample processing; mass spectrometry technologies, for differential proteome quantitation, analysis of post-translational modifications and imaging approaches in the brain are critically deliberated. Future directions, including analysis of cellular sub-compartments, targeted MS platforms (selected/parallel reaction monitoring) and use of mass cytometry are also discussed. Expert commentary: Here, we summarize and evaluate current mass spectrometry based approaches for determining brain dynamics in health and diseases states, with a focus on neurological disorders. Furthermore, we provide insight on current trends and new MS technologies with potential to improve this analysis.

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What Have Mass Spectrometry-Based Proteomics and Metabolomics (Not) Taught Us about Psychiatric Disorders?

Cited by 15 publications

References 79 publications

Unraveling the Serum Metabolomic Profile of Post-partum Depression

Unraveling the Serum Metabolomic Profile of Post-partum Depression

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

Recent advances in applying mass spectrometry and systems biology to determine brain dynamics

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