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Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children
BACKGROUND: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures o...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579334/ https://www.ncbi.nlm.nih.gov/pubmed/30878195 http://dx.doi.org/10.1016/j.biopsych.2019.01.018 |
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author | Madrid-Gambin, Francisco Föcking, Melanie Sabherwal, Sophie Heurich, Meike English, Jane A. O’Gorman, Aoife Suvitaival, Tommi Ahonen, Linda Cannon, Mary Lewis, Glyn Mattila, Ismo Scaife, Caitriona Madden, Sean Hyötyläinen, Tuulia Orešič, Matej Zammit, Stanley Cagney, Gerard Cotter, David R. Brennan, Lorraine |
author_facet | Madrid-Gambin, Francisco Föcking, Melanie Sabherwal, Sophie Heurich, Meike English, Jane A. O’Gorman, Aoife Suvitaival, Tommi Ahonen, Linda Cannon, Mary Lewis, Glyn Mattila, Ismo Scaife, Caitriona Madden, Sean Hyötyläinen, Tuulia Orešič, Matej Zammit, Stanley Cagney, Gerard Cotter, David R. Brennan, Lorraine |
author_sort | Madrid-Gambin, Francisco |
collection | PubMed |
description | BACKGROUND: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort. METHODS: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches. We assessed the lipids, lysophosphatidylcholines (n = 11) and phosphatidylcholines (n = 61), and the protein members of the coagulation pathway (n = 22) and integrated these data with complement pathway protein data already available on these subjects. RESULTS: Twelve phosphatidylcholines, four lysophosphatidylcholines, and the coagulation protein plasminogen were altered between the control and PEs groups after correction for multiple comparisons. Lipidomic and proteomic datasets were integrated into a multivariate network displaying a strong relationship between most lipids that were significantly associated with PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters, with one of the clusters presenting the highest case-control ratio (p < .01) and associated with a higher concentration of smaller low-density lipoprotein cholesterol particles. CONCLUSIONS: Our findings indicate that the lipidome and proteome of subjects who report PEs at 18 years of age are already altered at 12 years of age, indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting crosstalk between these lysophosphatidylcholines, phosphatidylcholines, and coagulation and complement proteins. |
format | Online Article Text |
id | pubmed-6579334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-65793342019-08-07 Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children Madrid-Gambin, Francisco Föcking, Melanie Sabherwal, Sophie Heurich, Meike English, Jane A. O’Gorman, Aoife Suvitaival, Tommi Ahonen, Linda Cannon, Mary Lewis, Glyn Mattila, Ismo Scaife, Caitriona Madden, Sean Hyötyläinen, Tuulia Orešič, Matej Zammit, Stanley Cagney, Gerard Cotter, David R. Brennan, Lorraine Biol Psychiatry Article BACKGROUND: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort. METHODS: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches. We assessed the lipids, lysophosphatidylcholines (n = 11) and phosphatidylcholines (n = 61), and the protein members of the coagulation pathway (n = 22) and integrated these data with complement pathway protein data already available on these subjects. RESULTS: Twelve phosphatidylcholines, four lysophosphatidylcholines, and the coagulation protein plasminogen were altered between the control and PEs groups after correction for multiple comparisons. Lipidomic and proteomic datasets were integrated into a multivariate network displaying a strong relationship between most lipids that were significantly associated with PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters, with one of the clusters presenting the highest case-control ratio (p < .01) and associated with a higher concentration of smaller low-density lipoprotein cholesterol particles. CONCLUSIONS: Our findings indicate that the lipidome and proteome of subjects who report PEs at 18 years of age are already altered at 12 years of age, indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting crosstalk between these lysophosphatidylcholines, phosphatidylcholines, and coagulation and complement proteins. Elsevier 2019-07-01 /pmc/articles/PMC6579334/ /pubmed/30878195 http://dx.doi.org/10.1016/j.biopsych.2019.01.018 Text en © 2019 by Society of Biological Psychiatry. All rights reserved. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Madrid-Gambin, Francisco Föcking, Melanie Sabherwal, Sophie Heurich, Meike English, Jane A. O’Gorman, Aoife Suvitaival, Tommi Ahonen, Linda Cannon, Mary Lewis, Glyn Mattila, Ismo Scaife, Caitriona Madden, Sean Hyötyläinen, Tuulia Orešič, Matej Zammit, Stanley Cagney, Gerard Cotter, David R. Brennan, Lorraine Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children |
title | Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children |
title_full | Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children |
title_fullStr | Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children |
title_full_unstemmed | Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children |
title_short | Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children |
title_sort | integrated lipidomics and proteomics point to early blood-based changes in childhood preceding later development of psychotic experiences: evidence from the avon longitudinal study of parents and children |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579334/ https://www.ncbi.nlm.nih.gov/pubmed/30878195 http://dx.doi.org/10.1016/j.biopsych.2019.01.018 |
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