Metabolomic biomarkers for (R, S)‐ketamine and (S)‐ketamine in treatment‐resistant depression and healthy controls: A systematic review

Bipolar Disorders, Journal Year: 2024, Volume and Issue: 26(4), P. 321 - 330

Published: Feb. 7, 2024

Abstract Background Ketamine is increasingly used for treatment‐resistant depression (TRD) while its mechanism of action still being investigated. In this systematic review, we appraise the current evidence metabolomic biomarkers racemic ketamine and esketamine in patients with TRD healthy controls (HCs). Methods A comprehensive search several databases (Ovid MEDLINE®, Embase, Epub Ahead Print) was performed from each database's inception to June 29, 2022, any language, conducted. We included studies wherein or were investigated HCs. Our main outcomes examine changes metabolites among treated ketamine/esketamine explore association response ketamine/esketamine. Results total 1859 abstracts screened which 11 full‐text review. Of these, a five articles ( N = 147), including three RCTs n 129) two open‐label trials 18). All ketamine; one study additionally esketamine. The evaluated bipolar 22), unipolar 91), HCs 34). reported alteration acylcarnitines, lipids, kynurenine (KYN), arginine TRD. Studies suggest involvement energy metabolism, KYN, pathways. HCs, acetylcarnitine decreased post‐infusion, whereas inconsistent findings observed after infusion patients. Conclusions This review provides preliminary that may cause important pathways involved metabolism inflammation. Larger more rigorous are needed.

Language: Английский

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An exploratory metabolomic comparison of participants with fast or absent functional progression from 2CARE, a randomized, double-blind clinical trial in Huntington’s disease

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 11, 2024

Huntington's disease (HD) is increasingly recognized for diverse pathology outside of the nervous system. To describe biology HD in relation to functional progression, we previously analyzed plasma and CSF metabolome a cross-sectional study participants who had various degrees impairment. Here, carried out an exploratory from individuals over 3-year time frame assess whether differences exist between those with fast or absent clinical progression. There were more circulating metabolite levels progressors compared (111 vs 20, nominal p < 0.05). All changes faster decreases, whereas some concentrations increased progressors. Many that decreased higher at Screening but ended up lower by Year 3. Changes progression suggest greater oxidative stress inflammation (kynurenine, diacylglycerides, cysteine), disturbances nitric oxide urea metabolism (arginine, citrulline, ornithine, GABR), polyamines (putrescine spermine), elevated glucose, deficient AMPK signaling. Metabolomic possibility predicting decline HD, possibly delaying it interventions augment arginine, polyamines, glucose regulation.

Language: Английский

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Evidence from preclinical and clinical metabolomics studies on the antidepressant effects of ketamine and esketamine

Neuroscience Letters, Journal Year: 2024, Volume and Issue: 831, P. 137791 - 137791

Published: April 24, 2024

The antidepressant effects of ketamine and esketamine are well-documented. Nonetheless, most the underlying molecular mechanisms have to be uncovered yet. In last decade, metabolomics has emerged as a useful means investigate metabolic phenotype associated with depression well changes induced by treatments. This mini-review aims at summarizing main findings from preclinical clinical studies that used subanesthetic, doses their relationship response. Both animal human report alterations in several pathways – including tricarboxylic acid cycle, glycolysis, pentose phosphate pathway, lipid metabolism, amino kynurenine urea cycle following administration or its enantiomers. Although more research is needed clarify commonalities differences action between racemic compound enantiomers, these comprehensively support an influence on mitochondrial cellular energy production, membrane homeostasis, neurotransmission, signaling. Metabolomics may thus represent promising strategy treatment-resistant related markers response esketamine. body evidence, if further substantiated, potential guide clinicians towards personalized approaches, contributing new paradigms management depression.

Language: Английский

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Cross‐sectional analysis of healthy individuals across decades: Aging signatures across multiple physiological compartments

Aging Cell, Journal Year: 2023, Volume and Issue: 23(1)

Published: June 23, 2023

Abstract The study of age‐related biomarkers from different biofluids and tissues within the same individual might provide a more comprehensive understanding changes between compartments as these are likely highly interconnected. Understanding differences by may shed light on mechanism their reciprocal interactions, which contribute to phenotypic manifestations aging. To such possible we carried out targeted metabolomic analysis plasma, skeletal muscle, urine collected healthy participants, age 22–92 years, identified 92, 34, 35 age‐associated metabolites, respectively. metabolic pathways that were across included inflammation cellular senescence, microbial metabolism, mitochondrial health, sphingolipid lysosomal membrane permeabilization, vascular aging, kidney function.

Language: Английский

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Cerebrospinal fluid metabolomes of treatment-resistant depression subtypes and ketamine response: a pilot study

Discover Mental Health, Journal Year: 2024, Volume and Issue: 4(1)

Published: April 17, 2024

Abstract Depression is a disorder with variable presentation. Selecting treatments and dose-finding is, therefore, challenging time-consuming. In addition, novel antidepressants such as ketamine have sparse optimization evidence. Insights obtained from metabolomics may improve the management of patients. The objective this study was to determine whether compounds in cerebrospinal fluid (CSF) metabolome correlate scores on questionnaires response medication. We performed retrospective pilot evaluate phenotypic metabolomic variability patients treatment-resistant depression using multivariate data compression algorithms. Twenty-nine provided fasting CSF samples. Over 300 metabolites were analyzed these samples liquid chromatography-mass spectrometry. Chart review basic demographic information, clinical status self-reported questionnaires, Of analyzed, 151 present all used analyses. Hypothesis-free analysis compressed resultant set into two dimensions Principal Component (PC) analysis, accounting for ~ 32% variance. PC1 accounted 16.9% variance strongly correlated age one direction 5-methyltetrahydrofolate, homocarnosine, anxiety opposite direction. PC2 15.4% variance, end autism scores, male gender, cognitive fatigue other bipolar diagnosis, lithium use, ethylmalonate disturbance. This small suggests that complex can be mapped onto 2-dimensional pathophysiological domain. results implications treatment selection subtypes.

Language: Английский

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The N -methyl- d -aspartate receptor hypothesis of ketamine’s antidepressant action: evidence and controversies

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1906)

Published: June 10, 2024

Substantial clinical evidence has unravelled the superior antidepressant efficacy of ketamine: in comparison to traditional antidepressants targeting monoamine systems, ketamine, as an

Language: Английский

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Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Physical function declines with aging, yet there is considerable heterogeneity, some individuals declining very slowly while others experience accelerated functional decline. To gain insight into mechanisms promoting high physical we performed proteomics, targeted metabolomics, and kynurenine-focused metabolomic analyses on serum specimens from three groups of octogenarians: High-functioning master athletes (HF, n = 16), healthy normal-functioning non-athletes (NF, 12), lower functioning (LF, 11). Higher performance status was associated evidence consistent with: Lower levels circulating proinflammatory markers, as well unperturbed tryptophan metabolism, the normal kynurenic pathway; higher lysophosphatidylcholines that have been previously better mitochondrial oxidative capacity; activity integrated stress response; SASP protein members; proteins reflect neurodegeneration/denervation. Extending observations previous studies focused biomarkers aging predict poor function, our findings show many same exhibit attenuated changes in those who maintain a function. Because cross-sectional nature this study, results should be interpreted caution, bidirectional causality, where behavior both cause outcome differences biomarker changes, remains possible interpretation.

Language: Английский

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High-performance liquid chromatography–tandem mass spectrometry for simultaneous determination of 23 antidepressants and active metabolites in human serum and its application in therapeutic drug monitoring

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 27, 2025

Introduction The incidence and mortality rate from depression are increasing year by year, has become the main cause of global health loss disability. Currently, treatment mainly relies on drug intervention. However, vast majority antidepressants exhibit significant pharmacological variability, resulting in individual differences steady-state blood concentrations even with same dosing regimen among patients. Therefore, using therapeutic monitoring (TDM) to guide precise use important clinical significance. Methods In this paper, we developed a high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method study simultaneously TDM pharmacokinetics 23 active metabolites: sertraline, escitalopram, fluvoxamine, paroxetine, duloxetine, milnacipran, fluoxetine, venlafaxine, O-desmethylvenlafaxine, mirtazapine, trazodone, bupropion, hydroxybupropione, norfluoxetine, vortioxetine, agomelatine, mianserin, doxepine, desmethyldoxepin, clomipramine, desmethylclomipramine, amitriptyline nortriptyline hydrochloride. After protein precipitation serum samples acetonitrile, isotope internal standards (ISs), metabolites were separated ZORBAX Eclipse Plus C18 column (50.0 mm × 2.1 mm, 1.7 µm) water containing 0.1% formic acid 10 mmol/L ammonium acetate methanol acid. Validation was carried out based Chinese Pharmacopoeia guidelines for bioanalytical validation, including assessment specificity, calibration curves, carryover, accuracy, crosstalk, precision, stability, recovery, dilution integrity matrix effect. Results results showed that simple, fast, reliable specific HPLC'MS/MS validated, all performance characteristics met requirements, which could be used above metabolites.

Language: Английский

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Alterations of serum metabolic profile in major depressive disorder: A case-control study in the Chinese population

World Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 15(5)

Published: April 30, 2025

BACKGROUND Major depressive disorder (MDD) is characterized by persistent depressed mood and cognitive symptoms. This study aimed to discover biomarkers for MDD, explore its pathological mechanisms, examine the associations of identified with clinical psychological variables. AIM To candidate MDD identification provide insight into mechanism MDD. METHODS The current adopted a single-center cross-sectional case-control design. Serum samples were obtained from 100 individuals diagnosed 97 healthy controls (HCs) aged between 18 60 years. Metabolomics was performed on an Ultimate 3000 UHPLC system coupled Q-Exactive MS (Thermo Scientific). online software Metaboanalyst 6.0 used process analyze acquired raw data peak intensities instrument. RESULTS included patients HCs. Metabolomic profiling 35 significantly different metabolites (e.g. , cortisol, sebacic acid, L-glutamic acid). Receiver operating characteristic curve analysis highlighted 8-HETE, 10-HDoHE, 12-HHTrE, 10-hydroxydecanoic acid as top diagnostic Significant correlations found some lipids, steroids, amino acids) CONCLUSION Our reported (some acids, carnitines, alkaloids) responsible discriminating metabolite profile may enable development laboratory-based test mechanisms underlying association or variables differential deserve further exploration.

Language: Английский

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Prefrontal Cortex Molecular Signatures of Chronically Socially Isolated Rats and Their Response to Fluoxetine Treatment

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Language: Английский

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