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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
Study ID | ST001098 |
Study Title | Metabolomics of Metabolic Risk in Patients Taking Atypical Antipsychotics (part II) |
Study 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 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 Name | Stringer |
First Name | Kathleen |
Address | 428 Church St |
NMRmetabolomics@umich.edu | |
Phone | 7346474775 |
Submit Date | 2018-11-15 |
Analysis Type Detail | GC-MS |
Release Date | 2019-01-22 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
mb_sample_id | local_sample_id | Treatment |
---|---|---|
SA074882 | CCMB_17 | Non-obese control |
SA074883 | CCMB_15 | Non-obese control |
SA074884 | CCMB_05 | Non-obese control |
SA074885 | CCMB_19 | Non-obese control |
SA074886 | P2721_27 | Non-obese control |
SA074887 | P2721_40 | Non-obese control |
SA074888 | P2721_28 | Non-obese control |
SA074889 | CCMB_04 | Non-obese control |
SA074890 | P2721_23 | Non-obese control |
SA074891 | P2721_22 | Non-obese control |
SA074892 | Q077 | Obese control |
SA074893 | Q025 | Obese control |
SA074894 | Q897 | Obese control |
SA074895 | Q005 | Obese control |
SA074896 | Q308 | Obese control |
SA074897 | Q160 | Obese control |
SA074898 | Q442 | Obese control |
SA074899 | Q632 | Obese control |
SA074900 | Q504 | Obese control |
SA074901 | Q610 | Obese control |
SA074902 | V158 | Schizophrenia dx |
SA074903 | V156 | Schizophrenia dx |
SA074904 | V154 | Schizophrenia dx |
SA074905 | V163 | Schizophrenia dx |
SA074906 | V151 | Schizophrenia dx |
SA074907 | V179 | Schizophrenia dx |
SA074908 | V149 | Schizophrenia dx |
SA074909 | V174 | Schizophrenia dx |
SA074910 | V172 | Schizophrenia dx |
SA074911 | V169 | Schizophrenia dx |
SA074912 | V165 | Schizophrenia dx |
SA074913 | V133 | Schizophrenia dx |
SA074914 | V138 | Schizophrenia dx |
SA074915 | V135 | Schizophrenia dx |
SA074916 | V134 | Schizophrenia dx |
SA074917 | V183 | Schizophrenia dx |
SA074918 | V139 | Schizophrenia dx |
SA074919 | V142 | Schizophrenia dx |
SA074920 | V147 | Schizophrenia dx |
SA074921 | V146 | Schizophrenia dx |
SA074922 | V144 | Schizophrenia dx |
SA074923 | V148 | Schizophrenia dx |
SA074924 | V214 | Schizophrenia dx |
SA074925 | V225 | Schizophrenia dx |
SA074926 | V224 | Schizophrenia dx |
SA074927 | V223 | Schizophrenia dx |
SA074928 | V221 | Schizophrenia dx |
SA074929 | V228 | Schizophrenia dx |
SA074930 | V232 | Schizophrenia dx |
SA074931 | V252 | Schizophrenia dx |
SA074932 | V250 | Schizophrenia dx |
SA074933 | V249 | Schizophrenia dx |
SA074934 | V241 | Schizophrenia dx |
SA074935 | V216 | Schizophrenia dx |
SA074936 | V215 | Schizophrenia dx |
SA074937 | V194 | Schizophrenia dx |
SA074938 | V193 | Schizophrenia dx |
SA074939 | V191 | Schizophrenia dx |
SA074940 | V190 | Schizophrenia dx |
SA074941 | V198 | Schizophrenia dx |
SA074942 | V202 | Schizophrenia dx |
SA074943 | V131 | Schizophrenia dx |
SA074944 | V212 | Schizophrenia dx |
SA074945 | V209 | Schizophrenia dx |
SA074946 | V205 | Schizophrenia dx |
SA074947 | V187 | Schizophrenia dx |
SA074948 | V092 | Schizophrenia dx |
SA074949 | V033 | Schizophrenia dx |
SA074950 | V032 | Schizophrenia dx |
SA074951 | V029 | Schizophrenia dx |
SA074952 | V023 | Schizophrenia dx |
SA074953 | V034 | Schizophrenia dx |
SA074954 | V035 | Schizophrenia dx |
SA074955 | V046 | Schizophrenia dx |
SA074956 | V045 | Schizophrenia dx |
SA074957 | V041 | Schizophrenia dx |
SA074958 | V037 | Schizophrenia dx |
SA074959 | V019 | Schizophrenia dx |
SA074960 | V018 | Schizophrenia dx |
SA074961 | V008 | Schizophrenia dx |
SA074962 | V004 | Schizophrenia dx |
SA074963 | V003 | Schizophrenia dx |
SA074964 | V001 | Schizophrenia dx |
SA074965 | V009 | Schizophrenia dx |
SA074966 | V011 | Schizophrenia dx |
SA074967 | V015 | Schizophrenia dx |
SA074968 | V014 | Schizophrenia dx |
SA074969 | V013 | Schizophrenia dx |
SA074970 | V012 | Schizophrenia dx |
SA074971 | V047 | Schizophrenia dx |
SA074972 | V048 | Schizophrenia dx |
SA074973 | V100 | Schizophrenia dx |
SA074974 | V097 | Schizophrenia dx |
SA074975 | V094 | Schizophrenia dx |
SA074976 | V089 | Schizophrenia dx |
SA074977 | V110 | Schizophrenia dx |
SA074978 | V115 | Schizophrenia dx |
SA074979 | V126 | Schizophrenia dx |
SA074980 | V123 | Schizophrenia dx |
SA074981 | V118 | Schizophrenia dx |
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 |
Instrument Name: | - |
Instrument Type: | - |
MS Type: | Other |
Ion Mode: | UNSPECIFIED |