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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

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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. In: Biological Psychiatry. 2019 ; Vol. 86, No. 1. pp. 25-34.

Bibtex

@article{9bd64b1e88924f21a2e2cf6d9a49191f,
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",
abstract = "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.",
keywords = "ALSPAC, Early life, Integration, Lipidomics, Proteomics, Psychotic episode",
author = "Francisco Madrid-Gambin and Melanie F{\"o}cking and Sophie Sabherwal and Meike Heurich and English, {Jane A} and Aoife O'Gorman and Tommi Suvitaival and Linda Ahonen and Mary Cannon and Glyn Lewis and Ismo Mattila and Caitriona Scaife and Sean Madden and Tuulia Hy{\"o}tyl{\"a}inen and Matej Orešič and Stanley Zammit and Gerard Cagney and Cotter, {David R} and Lorraine Brennan",
note = "Copyright {\circledC} 2019 Society of Biological Psychiatry. All rights reserved.",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.biopsych.2019.01.018",
language = "English",
volume = "86",
pages = "25--34",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier Inc",
number = "1",

}

RIS

TY - JOUR

T1 - Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences

T2 - Evidence From the Avon Longitudinal Study of Parents and Children

AU - Madrid-Gambin, Francisco

AU - Föcking, Melanie

AU - Sabherwal, Sophie

AU - Heurich, Meike

AU - English, Jane A

AU - O'Gorman, Aoife

AU - Suvitaival, Tommi

AU - Ahonen, Linda

AU - Cannon, Mary

AU - Lewis, Glyn

AU - Mattila, Ismo

AU - Scaife, Caitriona

AU - Madden, Sean

AU - Hyötyläinen, Tuulia

AU - Orešič, Matej

AU - Zammit, Stanley

AU - Cagney, Gerard

AU - Cotter, David R

AU - Brennan, Lorraine

N1 - Copyright © 2019 Society of Biological Psychiatry. All rights reserved.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

KW - ALSPAC

KW - Early life

KW - Integration

KW - Lipidomics

KW - Proteomics

KW - Psychotic episode

UR - http://www.scopus.com/inward/record.url?scp=85062721715&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2019.01.018

DO - 10.1016/j.biopsych.2019.01.018

M3 - Journal article

VL - 86

SP - 25

EP - 34

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 1

ER -

ID: 56844994