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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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posted on 12.03.2021, 11:53 by Francisco Madrid-Gambin, Melanie FockingMelanie Focking, Sophie Sabherwal, Meike Heurich, Jane A English, Aoife O'Gorman, Tommi Suvitaival, Linda Ahonen, Mary CannonMary Cannon, Glyn Lewis, Ismo Mattila, Caitriona Scaife, Sean Madden, Tuulia Hyötyläinen, Matej Orešič, Stanley Zammit, Gerard Cagney, David CotterDavid Cotter, Lorraine Brennan

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.

Funding

European Research Council Grant No. 647783

European Research Council Grant No. 724809 (iHEAR)

European Union FP7 collaborative project METSY Grant No. 602478

National Institute for Health Research Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol

Irish Health Research Board Clinician Scientist Award

The UK Medical Research Council and Wellcome Trust (102215/2/13/2)

University of Bristol (ALSPAC)

Health Research Board Grant Nos. HRA-POR-2013-282 and HRBCSA2012/8

History

Comments

The original article is available at https://www.biologicalpsychiatryjournal.com

Published Citation

Madrid-Gambin F, Föcking M, Sabherwal S, Heurich M, English JA, O'Gorman A, Suvitaival T, Ahonen L, Cannon M, Lewis G, Mattila I, Scaife C, Madden S, Hyötyläinen T, Orešič M, Zammit S, Cagney G, Cotter DR, Brennan L. 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. Biological Psychiatry. 2019;86(1):25-34.

Publication Date

30 January 2019

PubMed ID

30878195

Department/Unit

  • Beaumont Hospital
  • Psychiatry

Research Area

  • Neurological and Psychiatric Disorders

Publisher

Elsevier

Version

  • Published Version (Version of Record)