Summary of Study ST001098

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000734. The data can be accessed directly via it's Project DOI: 10.21228/M8SX1Q This work is supported by NIH grant, U2C- DK119886.

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Study IDST001098
Study TitleMetabolomics of Metabolic Risk in Patients Taking Atypical Antipsychotics (part II)
Study SummarySTUDY OBJECTIVE Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomics variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN Metabolomics analysis. PARTICIPANTS Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index range of the patients with schizophrenia to account for metabolite concentration differences attributable to body mass index. MEASUREMENTS AND MAIN RESULTS Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance (NMR) and gas chromatography (GC) methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 (interquartile range 41.0-52.0) years. Using a false discovery rate threshold of <25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward having higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION These results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration. This article is protected by copyright. All rights reserved. As published in Pharmacotherapy. 2018 Jun;38(6):638-650.
Institute
University of Michigan
Last NameStringer
First NameKathleen
Address428 Church St
EmailNMRmetabolomics@umich.edu
Phone7346474775
Submit Date2018-11-15
Analysis Type DetailGC-MS
Release Date2019-01-22
Release Version1
Kathleen Stringer Kathleen Stringer
https://dx.doi.org/10.21228/M8SX1Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000734
Project DOI:doi: 10.21228/M8SX1Q
Project Title:Metabolomics of Metabolic Risk in Patients Taking Atypical Antipsychotics
Project Type:Quantitative NMR and TLC-GC fatty acid analysis
Project Summary:STUDY OBJECTIVE Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomic variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN Metabolomics analysis. PARTICIPANTS Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index range of the patients with schizophrenia to account for metabolite concentration differences attributable to body mass index. MEASUREMENTS AND MAIN RESULTS Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance (NMR) and gas chromatography (GC) methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 (interquartile range 41.0-52.0) years. Using a false discovery rate threshold of <25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward having higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION These results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration. This article is protected by copyright. All rights reserved. As published in Pharmacotherapy. 2018 Jun;38(6):638-650.
Institute:University of Michigan
Department:Clinical Pharmacy
Laboratory:University of Michigan NMR Metabolomics Core
Last Name:Stringer
First Name:Kathleen
Address:428 Church St
Email:NMRmetabolomics@umich.edu
Phone:734-647-4775
Funding Source:Funding for this work was supported in part by grants from the following centers: the University of Michigan Claude D. Pepper Older Americans Independence Center (National Institute on Aging [NIA] grantAGA024824); the University of Michigan’s Nutrition Obesity Research Center (grant DK089503) and Weight Management Program, and the Michigan Regional Comprehensive Metabolomics Resource Core (grant DK097153),the Michigan Center for Diabetes Translational Research(grant P30DK092926), and the A. Alfred Taubman Medical Institute and the Robert C. and Veronica Atkins Foundation. This work was also supported in part by a metabolomics supplement to a grant from the National Institute of Mental Health (NIMH; grant MH082784; Dr. Ellingrod).Dr. Stringer’s effort is supported in part by a grant from the National Institute of General Medical Sciences (NIGMS; grant GM111400). Dr. Rothberg’s effort is supported in part by DK089503.
Publications:Pharmacotherapy. 2018 Jun;38(6):638-650

Subject:

Subject ID:SU001142
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:30-60 years old
Weight Or Weight Range:52.3-176.6 kg
Gender:Male and female
Human Medications:To be included in the study all participants had to be taking an atypical (second-generation) antipsychotic
Human Inclusion Criteria:DSM IV diagnosis of a schizophrenia spectrum diagnosis who had been taking an atypical antipsychotic for at least 6 months, with no changes in antipsychotic regimen for 8 weeks preceding the baseline visit. Twenty age and sex matched obese and nonobese participants without mental health diagnoses were included to match the BMI range of the patients with schizophrenia as BMI controls.
Human Exclusion Criteria:Current use of insulin, diagnosis of diabetes mellitus type 2 prior to antipsychotic exposure, active substance abuse diagnosis

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA074882CCMB_17Non-obese control
SA074883CCMB_15Non-obese control
SA074884CCMB_05Non-obese control
SA074885CCMB_19Non-obese control
SA074886P2721_27Non-obese control
SA074887P2721_40Non-obese control
SA074888P2721_28Non-obese control
SA074889CCMB_04Non-obese control
SA074890P2721_23Non-obese control
SA074891P2721_22Non-obese control
SA074892Q077Obese control
SA074893Q025Obese control
SA074894Q897Obese control
SA074895Q005Obese control
SA074896Q308Obese control
SA074897Q160Obese control
SA074898Q442Obese control
SA074899Q632Obese control
SA074900Q504Obese control
SA074901Q610Obese control
SA074902V158Schizophrenia dx
SA074903V156Schizophrenia dx
SA074904V154Schizophrenia dx
SA074905V163Schizophrenia dx
SA074906V151Schizophrenia dx
SA074907V179Schizophrenia dx
SA074908V149Schizophrenia dx
SA074909V174Schizophrenia dx
SA074910V172Schizophrenia dx
SA074911V169Schizophrenia dx
SA074912V165Schizophrenia dx
SA074913V133Schizophrenia dx
SA074914V138Schizophrenia dx
SA074915V135Schizophrenia dx
SA074916V134Schizophrenia dx
SA074917V183Schizophrenia dx
SA074918V139Schizophrenia dx
SA074919V142Schizophrenia dx
SA074920V147Schizophrenia dx
SA074921V146Schizophrenia dx
SA074922V144Schizophrenia dx
SA074923V148Schizophrenia dx
SA074924V214Schizophrenia dx
SA074925V225Schizophrenia dx
SA074926V224Schizophrenia dx
SA074927V223Schizophrenia dx
SA074928V221Schizophrenia dx
SA074929V228Schizophrenia dx
SA074930V232Schizophrenia dx
SA074931V252Schizophrenia dx
SA074932V250Schizophrenia dx
SA074933V249Schizophrenia dx
SA074934V241Schizophrenia dx
SA074935V216Schizophrenia dx
SA074936V215Schizophrenia dx
SA074937V194Schizophrenia dx
SA074938V193Schizophrenia dx
SA074939V191Schizophrenia dx
SA074940V190Schizophrenia dx
SA074941V198Schizophrenia dx
SA074942V202Schizophrenia dx
SA074943V131Schizophrenia dx
SA074944V212Schizophrenia dx
SA074945V209Schizophrenia dx
SA074946V205Schizophrenia dx
SA074947V187Schizophrenia dx
SA074948V092Schizophrenia dx
SA074949V033Schizophrenia dx
SA074950V032Schizophrenia dx
SA074951V029Schizophrenia dx
SA074952V023Schizophrenia dx
SA074953V034Schizophrenia dx
SA074954V035Schizophrenia dx
SA074955V046Schizophrenia dx
SA074956V045Schizophrenia dx
SA074957V041Schizophrenia dx
SA074958V037Schizophrenia dx
SA074959V019Schizophrenia dx
SA074960V018Schizophrenia dx
SA074961V008Schizophrenia dx
SA074962V004Schizophrenia dx
SA074963V003Schizophrenia dx
SA074964V001Schizophrenia dx
SA074965V009Schizophrenia dx
SA074966V011Schizophrenia dx
SA074967V015Schizophrenia dx
SA074968V014Schizophrenia dx
SA074969V013Schizophrenia dx
SA074970V012Schizophrenia dx
SA074971V047Schizophrenia dx
SA074972V048Schizophrenia dx
SA074973V100Schizophrenia dx
SA074974V097Schizophrenia dx
SA074975V094Schizophrenia dx
SA074976V089Schizophrenia dx
SA074977V110Schizophrenia dx
SA074978V115Schizophrenia dx
SA074979V126Schizophrenia dx
SA074980V123Schizophrenia dx
SA074981V118Schizophrenia dx
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Collection:

Collection ID:CO001136
Collection Summary:Fasting blood samples were collected via venipuncture into an additive-free vial and allowed to coagulate at room temperature for 30 minutes. They were then centrifuged for 15 minutes at 2500 rcf to obtain serum. Samples were frozen and -80C, thawed once for sample processing related to the parent study, then kept at -80C until processing for NMR and GC assays
Sample Type:Blood (serum)
Storage Conditions:-80℃
Collection Vials:Additive-free vacuatiner

Treatment:

Treatment ID:TR001156
Treatment Summary:N/A (observational study)

Sample Preparation:

Sampleprep ID:SP001149
Sampleprep Summary:Serum samples were subjected to a 1:1 methanol:choloroform extraction, then dried with a speedvac. Prior to fatty acid analysis, the lipid fractions were resuspended and purified by TLC prior to GC analysis. This is described in more detail in the attached document, with sample prep summaries for the NMR component of this study included as well.
Sampleprep Protocol ID:EllingrodSamplePrepProtocol
Sampleprep Protocol Filename:EllingrodSamplePrepProtocols.pdf
Extraction Method:1:1 methanol:chloroform
Sample Resuspension:hexane
Sample Spiking:C17:0 methyl ester

Combined analysis:

Analysis ID AN001786
Analysis type MS
Chromatography type GC
Chromatography system Agilent 6890N
Column Unspecified
MS Type Other
MS instrument type
MS instrument name
Ion Mode UNSPECIFIED
Units nmol

Chromatography:

Chromatography ID:CH001261
Instrument Name:Agilent 6890N
Column Name:Unspecified
Chromatography Type:GC

MS:

MS ID:MS001649
Analysis ID:AN001786
MS Type:Other
Ion Mode:UNSPECIFIED
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