An Untargeted Metabolomics Analysis of Antipsychotic Use in Bipolar Disorder.
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ABSTRACT:
SUBMITTER: Burghardt KJ
PROVIDER: S-EPMC4626284 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionObsessive-compulsive disorder (OCD), characterized by the presence of obsessions and/or compulsions, is often difficult to diagnose and treat in routine clinical practice. The candidate circulating biomarkers and primary metabolic pathway alteration of plasma in OCD remain poorly understood.MethodsWe recruited 32 drug-naïve patients with severe OCD and 32 compared healthy controls and applied the untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to assess their circulating metabolic profiles. Both univariate and multivariate analyses were then utilized to filtrate differential metabolites between patients and healthy controls, and weighted Correlation Network Analysis (WGCNA) was utilized to screen out hub metabolites.ResultsA total of 929 metabolites were identified, including 34 differential metabolites and 51 hub metabolites, with an overlap of 13 metabolites. Notably, the following enrichment analyses underlined the importance of unsaturated fatty acids and tryptophan metabolism alterations in OCD. Metabolites of these pathways in plasma appeared to be promising biomarkers, such as Docosapentaenoic acid and 5-Hydroxytryptophan, which may be biomarkers for OCD identification and prediction of sertraline treatment outcome, respectively.ConclusionOur findings revealed alterations in the circulating metabolome and the potential utility of plasma metabolites as promising biomarkers in OCD.
| S-EPMC10272357 | biostudies-literature
Project description:BackgroundNon-adherence is a significant problem in bipolar disorder. Second-generation antipsychotics (SGA) long-acting injections (LAIs) may improve adherence in bipolar disorder and may prevent relapses. However, the evidence is limited and conflicting.ObjectiveThe objective of this study was to evaluate efficacy and safety of SGA LAIs in bipolar disorder.MethodSystematic review and meta-analysis of randomised controlled trials (RCTs) (≥6 months duration) investigating safety and efficacy of SGA LAIs for bipolar disorder. We searched Pubmed, Embase, CINAHL, Cochrane, PsycINFO, LiLACS, www.clinicaltrials.gov up to October 2016. We also contacted the manufacturers of SGA LAIs. Primary efficacy and safety outcomes were relapse rate and all-cause discontinuation respectively.ResultsTotal of seven RCTs (n = 1192) were included. SGA LAIs show superiority over placebo for study-defined relapse rate (RR = 0.58, 95% CI = 0.49-0.68, P < 0.00001) and all-cause discontinuation (RR = 0.72, 95% CI = 0.64-0.82, P < 0.00001). However, no significant difference was found between SGA LAIs and oral active control for relapse rate (RR = 0.92, P = 0.79) and all-cause discontinuation (RR = 1.2, P = 0.31). In terms of secondary outcomes, SGA LAIs performed better than placebo in relapse to mania/hypomania, young mania rating scales (YMRS), clinical global impression-severity (CGI-S), montgomery-asberg depression rating scale (MADRS). There was no significant difference between SGA LAIs and oral active control regarding relapse to mania/hypomania, YMRS, CGI-S, extra-pyramidal side effects (EPSEs), weight gain. However, the active control performed better than SGA LAIs in relapse to depression, MADRS, and prolactin-related AEs.ConclusionsCurrent evidence is very limited to support the use of SGA LAIs (compared to oral medication) in bipolar disorder. Further high-quality studies, particularly comparing SGA LAIs with active control, are warranted.
| S-EPMC6587954 | biostudies-literature
Project description:ObjectivesNursing home quality measures include the proportion of residents who receive antipsychotics. Residents with bipolar disorder are included even though antipsychotics are FDA-approved for this indication. We evaluated how including residents with bipolar disorder impacted the antipsychotic use quality measure for long-stay residents. We evaluated the agreement of minimum data set (MDS) bipolar disorder diagnoses with Medicare data, whether dementia was diagnosed before bipolar disorder, and how less-specific bipolar disorder diagnoses impacted findings.DesignCross-sectional study.SettingNursing homes in Iowa.Participants21,955 long-stay nursing home residents in the first quarter of 2014.MeasurementsWe identified antipsychotic use and bipolar disorder using MDS data. We compared MDS bipolar disorder diagnoses with Chronic Conditions Warehouse (CCW) "ever" bipolar disorder indicators, and prior year claims. We compared CCW condition onset dates to identify bipolar disorder diagnosed after dementia.ResultsThe mean (SD) proportion receiving antipsychotics was 19.6% (11.1%) with bipolar disorder and 18.3% (10.8%) without. The positive predictive value (PPV) of MDS bipolar disorder diagnoses was 80.2% versus CCW lifetime indicators, and 74.6% versus claims. PPV decreased by 27.1% when "bipolar disorder, unspecified" and "other bipolar disorders" diagnoses were excluded. Nearly three-quarters of residents with bipolar disorder had dementia. Over half of those with dementia had dementia first per CCW records. This proportion was lower among those with more specific bipolar disorder diagnoses or MDS bipolar disorder indicators.ConclusionsBipolar disorder in nursing home residents is often first diagnosed after dementia using nonspecific diagnoses. This practice deserves further evaluation.
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Project description:Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men.
| S-EPMC10051496 | biostudies-literature
Project description:The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic treatment and genetic regulation. Pharmacoepigenetics may some day assist in identifying treatment response mechanisms or become one of the components in the implementation of precision medicine. To understand the current evidence regarding the effects of antipsychotics on DNA methylation a systematic review with qualitative synthesis was performed through Pubmed, Embase and Psychinfo from earliest data to June 2019. Studies were included if they analyzed DNA methylation in an antipsychotic-treated population of patients with schizophrenia or bipolar disorder. Data extraction occurred via a standardized format and study quality was assessed. Twenty-nine studies were identified for inclusion. Study design, antipsychotic type, sample source, and methods of DNA methylation measurement varied across all studies. Eighteen studies analyzed methylation in patients with schizophrenia, four studies in patients with bipolar disorder, and seven studies in a combined sample of schizophrenia and bipolar disorder. Twenty-two studies used observational samples whereas the remainder used prospectively treated samples. Six studies assessed global methylation, five assessed epigenome-wide, and 15 performed a candidate epigenetic study. Two studies analyzed both global and gene-specific methylation, whereas one study performed a simultaneous epigenome-wide and gene-specific study. Only three genes were analyzed in more than one gene-specific study and the findings were discordant. The state of the pharmacoepigenetic literature on antipsychotic use is still in its early stages and uniform reporting of methylation site information is needed. Future work should concentrate on using prospective sampling with appropriate control groups and begin to replicate many of the novel associations that have been reported.
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Project description:The rapidly increasing number of engineered nanoparticles (NPs), and products containing NPs, raises concerns for human exposure and safety. With this increasing, and ever changing, catalogue of NPs it is becoming more difficult to adequately assess the toxic potential of new materials in a timely fashion. It is therefore important to develop methods which can provide high-throughput screening of biological responses. The use of omics technologies, including metabolomics, can play a vital role in this process by providing relatively fast, comprehensive, and cost-effective assessment of cellular responses. These techniques thus provide the opportunity to identify specific toxicity pathways and to generate hypotheses on how to reduce or abolish toxicity.We have used untargeted metabolome analysis to determine differentially expressed metabolites in human lung epithelial cells (A549) exposed to copper oxide nanoparticles (CuO NPs). Toxicity hypotheses were then generated based on the affected pathways, and critically tested using more conventional biochemical and cellular assays. CuO NPs induced regulation of metabolites involved in oxidative stress, hypertonic stress, and apoptosis. The involvement of oxidative stress was clarified more easily than apoptosis, which involved control experiments to confirm specific metabolites that could be used as standard markers for apoptosis; based on this we tentatively propose methylnicotinamide as a generic metabolic marker for apoptosis.Our findings are well aligned with the current literature on CuO NP toxicity. We thus believe that untargeted metabolomics profiling is a suitable tool for NP toxicity screening and hypothesis generation.
| S-EPMC5017021 | biostudies-other
Project description: Not available
| S-EPMC8705952 | biostudies-literature
Project description:90% of esophageal cancer are esophageal squamous cell carcinoma (ESCC) and ESCC has a very poor prognosis and high mortality. Nevertheless, the key metabolic pathways associated with ESCC progression haven't been revealed yet. Metabolomics has become a new platform for biomarker discovery over recent years. We aim to elucidate dominantly metabolic pathway in all ESCC tumor/node/metastasis (TNM) stages and adjacent cancerous tissues. We collected 60 postoperative esophageal tissues and 15 normal tissues adjacent to the tumor, then performed Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) analyses. The metabolites data was analyzed with metabolites differential and correlational expression heatmap according to stage I vs. con., stage I vs. stage II, stage II vs. stage III, and stage III vs. stage IV respectively. Metabolic pathways were acquired by Kyoto Encyclopedia of Genes and Genomes. (KEGG) pathway database. The metabolic pathway related genes were obtained via Gene Set Enrichment Analysis (GSEA). mRNA expression of ESCC metabolic pathway genes was detected by two public datasets: gene expression data series (GSE)23400 and The Cancer Genome Atlas (TCGA). Receiver operating characteristic curve (ROC) analysis is applied to metabolic pathway genes. 712 metabolites were identified in total. Glycerophospholipid metabolism was significantly distinct in ESCC progression. 16 genes of 77 genes of glycerophospholipid metabolism mRNA expression has differential significance between ESCC and normal controls. Phosphatidylserine synthase 1 (PTDSS1) and Lysophosphatidylcholine Acyltransferase1 (LPCAT1) had a good diagnostic value with Area under the ROC Curve (AUC) > 0.9 using ROC analysis. In this study, we identified glycerophospholipid metabolism was associated with the ESCC tumorigenesis and progression. Glycerophospholipid metabolism could be a potential therapeutic target of ESCC progression.
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Project description:Opioid use disorder (OUD) is diagnosed using the qualitative criteria defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Diagnostic biomarkers for OUD do not currently exist. Our study focused on developing objective biological markers to differentiate chronic opiate users with OUD from chronic opiate users without OUD. Using biospecimens from the Golestan Cohort Study, we compared the metabolomics profiles of high opium users who were diagnosed as OUD positive with high opium users who were diagnosed as OUD negative. High opium use was defined as maximum weekly opium usage greater than or equal to the median usage (2.4 g per week), and OUD was defined as having 2 or more DSM-5 criteria in any 12-month period. Among the 218 high opium users in this study, 80 were diagnosed as OUD negative, while 138 were diagnosed as OUD positive. Seven hundred and twelve peaks differentiated high opium users diagnosed as OUD positive from high opium users diagnosed as OUD negative. Stepwise logistic regression modeling of subject characteristics data together with the 712 differentiating peaks revealed a signature that is 95% predictive of an OUD positive diagnosis, a significant (p < 0.0001) improvement over a 63% accurate prediction based on subject characteristic data for these samples. These results suggest that a metabolic profile can be used to predict an OUD positive diagnosis.
| S-EPMC7862627 | biostudies-literature
Project description:BackgroundOral antipsychotic (AP) medications are frequently prescribed to people with bipolar I disorder (BD-I). A cross-sectional online survey examined the experiences of people living with BD-I with a history of recent AP use.MethodsAdults with self-reported physician-diagnosed BD-I (N = 200) who received oral APs during the prior year completed a survey on AP-related experiences, including side effects and their perceived burden on social functioning, adherence, and work. Items also assessed preferences for trade-offs (balancing symptom management and side effects) when considering a hypothetical new AP. The perceived impact of specific, prevalent side effects on adherence, work, and preferences for a hypothetical AP were also examined. Analyses were descriptive.ResultsThe survey sample had a mean age of 43.2 (SD = 12.4) years, was 60% female, and 31% nonwhite. Almost all participants (98%) had experienced AP side effects. Common self-reported side effects were feeling drowsy or tired (83%), lack of emotion (79%), anxiety (79%), dry mouth (76%), and weight gain (76%). Weight gain was cited as the most bothersome side effect, rated by most participants (68%) as "very" or "extremely bothersome." Nearly half of participants (49%) reported that AP side effects negatively impacted their job performance; almost all (92%) reported that side effects - most commonly anxiety and lack of emotion - negatively impacted social relationships (e.g., family or romantic partners). The most commonly-reported reason for stopping AP use was dislike of side effects (48%). Side effects most likely to lead to stopping or taking less of AP treatment included "feeling like a 'zombie'" (29%), feeling drowsy or tired (25%), and weight gain (24%). When considering a hypothetical new AP, the most common side effects participants wanted to avoid included AP-induced anxiety (50%), weight gain (48%), and "feeling like a 'zombie'" (47%).ConclusionsSide effects of APs were both common and bothersome, and impacted social functioning, adherence, and work. Findings highlight the prevailing unmet need for new APs with more favorable benefit-risk profiles.
| S-EPMC7371473 | biostudies-literature