Profiling of Amino Acids and Their Derivatives Biogenic Amines Before and After Antipsychotic Treatment in First-Episode Psychosis

Leppik, Liisa; Kriisa, Kärt; Koido, Kati; Koch, Kadri; Kajalaid, Kärolin; Haring, Liina; Vasar, Eero; Zilmer, Mihkel

doi:10.3389/fpsyt.2018.00155

Cited by 49 publications

(37 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have shown that the use of medication such as antidepressants and levodopa can influence Kyn metabolite concentrations (Myint et al ; Ara and Bano ; Kocki et al ; Gibney et al ; Eskelund et al ; Leppik et al ). Because medication data were not available for all patients, we first conducted sensitivity analyses to assess whether availability of medication use was associated with alterations of Kyn pathway metabolites.…”

Section: Resultsmentioning

confidence: 99%

“…Occurrence of LID is thus unlikely to have had a major influence on our results. Furthermore, clinical and preclinical models have demonstrated that antidepressants and anti‐psychotic drugs, which are commonly used by PD and AD patients, can modulate Kyn pathway activity (Myint et al ; Ara and Bano ; Kocki et al ; Gibney et al ; Eskelund et al ; Leppik et al ). Our results demonstrated that that the use of medication was not involved in the reduced KA content observed in CSF of PD and AD patients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Sorgdrager

Vermeiren

Faassen

et al. 2019

Journal of Neurochemistry

106

View full text Add to dashboard Cite

The kynurenine (Kyn) pathway, which regulates neuroinflammation and N‐methyl‐d‐aspartate receptor activation, is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD). Age‐related changes in Kyn metabolism and altered cerebral Kyn uptake along large neutral amino acid transporters, could contribute to these diseases. To gain further insight into the role and prognostic potential of the Kyn pathway in PD and AD, we investigated systemic and cerebral Kyn metabolite production and estimations of their transporter‐mediated uptake in the brain. Kyn metabolites and large neutral amino acids were retrospectively measured in serum and cerebrospinal fluid (CSF) of clinically well‐characterized PD patients (n = 33), AD patients (n = 33), and age‐matched controls (n = 39) using solid‐phase extraction‐liquid chromatographic‐tandem mass spectrometry. Aging was disease independently associated with increased Kyn, kynurenic acid and quinolinic acid in serum and CSF. Concentrations of kynurenic acid were reduced in CSF of PD and AD patients (p = 0.001; p = 0.002) but estimations of Kyn brain uptake did not differ between diseased and controls. Furthermore, serum Kyn and quinolinic acid levels strongly correlated with their respective content in CSF and Kyn in serum negatively correlated with AD disease severity (p = 0.002). Kyn metabolites accumulated with aging in serum and CSF similarly in PD patients, AD patients, and control subjects. In contrast, kynurenic acid was strongly reduced in CSF of PD and AD patients. Differential transporter‐mediated Kyn uptake is unlikely to majorly contribute to these cerebral Kyn pathway disturbances. We hypothesize that the combination of age‐ and disease‐specific changes in cerebral Kyn pathway activity could contribute to reduced neurogenesis and increased excitotoxicity in neurodegenerative disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Sorgdrager

Vermeiren

Faassen

et al. 2019

Journal of Neurochemistry

106

View full text Add to dashboard Cite

show abstract

“…Acetohydroxyacid synthase, ketol acid reductoisomerase (KARI), dihydroxyacid dehydratase (DHAD), and branched chain amino transferase (BCAT) were the four enzymes operating in L-isoleucine and L-valine biosynthesis (Galili et al, 2016). Abnormal changes in L-isoleucine and L-valine levels have been documented in firstepisode psychosis (Leppik et al, 2018). Our study suggested that abnormal changes in L-isoleucine and L-valine levels are also associated with MMD.…”

Section: Discussionmentioning

confidence: 69%

“…Amino acid levels in patients with various diseases often differ from those of healthy individuals. Alterations in plasma concentrations of amino acids have been reported in liver fibrosis, non-small-cell lung cancer, aortic dissection, first-episode psychosis, and type-2 diabetes mellitus in patients with coronary artery disease (Yang et al, 2013;Leppik et al, 2018). We found that levels of a panel of amino acids (L-alanine, L-isoleucine, L-valine, L-serine, L-threonine, L-methionine, Lphenylalanine, and L-tyrosine) were significantly different in MMD patients relative to HCs.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling Revealed Potential Biomarkers in Patients With Moyamoya Disease

Geng

Guo

Wang³

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

Metabolomics is increasingly used to observe metabolic patterns and disease-specific metabolic biomarkers. However, serum metabolite analysis of moyamoya disease (MMD) is rarely reported. We investigated serum metabolites in MMD and compared them with those of healthy controls (HCs) using a non-targeted gas chromatographymass spectrometry (GC-MS) approach to identify metabolic biomarkers associated with MMD. Forty-one patients with MMD diagnosed by cerebral angiography and 58 HCs were recruited for our study. Comparative analyses (univariate, multivariate, correlation, heatmaps, receiver operating characteristi curves) were performed between MMD patients and HCs. Twenty-five discriminating serum metabolic biomarkers between MMD patients and HCs were identified. Compared with HCs, MMD patients had higher levels of phenol, 2-hydroxybutyric acid, L-isoleucine, L-serine, glycerol, pelargonic acid, L-methionine, myristic acid, pyroglutamic acid, palmitic acid, palmitoleic acid, stearic acid, octadecanamide, monoglyceride (MG) (16:0/0:0/0:0), and MG (0:0/18:0/0:0), and lower levels of L-alanine, L-valine, urea, succinic acid, L-phenylalanine, L-threonine, L-tyrosine, edetic acid, and oleamide. These metabolic biomarkers are involved in several pathways and are closely associated with the metabolism of amino acids, lipids, carbohydrates, and carbohydrate translation. A GC-MS-based metabolomics approach could be useful in the clinical diagnosis of MMD. The identified biomarkers may be helpful to develop an objective diagnostic method for MMD and improve our understanding of MMD pathogenesis.

show abstract

“…Аминокислоты и ацилкарнитины как потенциальные метаболомные маркеры Обзоры и лекции ÷åñêîé òåðàïèè. Íàïðîòèâ, ñîäåðaeàíèå òàóðèíà è ñïåðìèíà áûëî îòðèöàòåëüíî àññîöèèðîâàíî ñ ïîâûøåíèåì ÈÌÒ â ïðîöåññå ôàðìàêîòåðàïèè [51]. Òàêèì îáðàçîì, èññëåäîâàíèÿ ðîëè àìèíîêèñëîò â ðàçâèòèè íåaeåëàòåëüíûõ òÿaeåëûõ ïîáî÷íûõ ýôôåêòîâ àíòèïñèõîòè÷åñêîé òåðàïèè ïðàêòè÷åñêè îòñóòñòâóþò, çà èñêëþ÷åíèåì èññëåäîâàíèé ãëóòàìàòà, â îòíîøåíèè êîòîðîãî ÿâëÿåòñÿ äîêàçàííûì ôàêò åãî ó÷àñòèÿ â ìåõàíèçìàõ ðàçâèòèÿ òàðäèâíîé äèñêèíåçèè [52].…”

Section: аминокислоты как маркеры терапевтического ответа на антипсихunclassified

Amino acids and acylcarnitines as potential metabolomic markers of schizophrenia: new approaches to diagnostics and therapy

et al. 2020

View full text Add to dashboard Cite

Background. Schizophrenia is a socially significant mental illness with insufficiently studied etiology and pathogenesis. A number of hypotheses of schizophrenia pathogenesis (dopamine, glutamate, kinurenin and serotonin hypotheses) bring together the fact that amino acids are precursors or intermediate metabolic products of these metabolites. Amino acids and their metabolites play an important role as significant substrates and regulators in many metabolic pathways.The aim of this review is to analyze the literature data on the studies of amino acids and acylcarnitines in patients with schizophrenia.Methods. A literature search was conducted using PubMed databases for articles published in English and covering the period from the first articles on this topic, dated 1977 to April 2019. Combinations of the following keywords were used to search for “schizophrenia”, “antipsychotics” and “amino acids”, “acylcarnitines”, “metabolomics”.Results. The review summarizes the data on the content of amino acids and acylcarnitines in the peripheral blood of schizophrenia patients and their dynamics in the course of pharmacotherapy with antipsychotic drugs. The potential of determining amino acids as biomarkers of therapeutic response and side effects, as well as their use in the treatment of patients with schizophrenia, are considered.Conclusion. Further investigation of the spectrum of amino acids and their metabolites with the using of mass spectrometric methods of metabolic analysis can lead to the discovery of new therapeutic targets and strategies, assess their role in the pathophysiology of schizophrenia, identify mechanisms that ensure the development of antipsychotic antipsychotics, and drug-induced side effects antipsychotics, in particular, metabolic syndrome.

show abstract

Profiling of Amino Acids and Their Derivatives Biogenic Amines Before and After Antipsychotic Treatment in First-Episode Psychosis

Cited by 49 publications

References 69 publications

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Metabolomic Profiling Revealed Potential Biomarkers in Patients With Moyamoya Disease

Amino acids and acylcarnitines as potential metabolomic markers of schizophrenia: new approaches to diagnostics and therapy

Contact Info

Product

Resources

About