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

Francisco Madrid-Gambin, Melanie Föcking, Sophie Sabherwal, Meike Heurich, Jane English, Aoife O'Gorman, Tommi Suvitaival, Linda Ahonen, Mary Cannon, Glynn Lewis, Ismo Mattila, Caitriona Scaife, Sean Madden, Tuulia Hyotylainen, Matej Oresic, Stan Zammit, Gerard Cagney, David R Cotter, Lorraine Brennan

Research output: Contribution to journalArticle (Academic Journal)

4 Citations (Scopus)
223 Downloads (Pure)

Abstract

Background: The identification of early biomarkers of psychotic experiences (PEs) is of interest as 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 (age 12) who were first identified as experiencing PEs at age 18 (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semi-targeted proteomics approaches. We assessed the lipids, LPCs (n=11) and PCs (n=61), and the protein members of the coagulation pathway (n=22) and integrated this data with complement pathway protein data already available on these subjects. Results: Twelve PCs, four LPCs and the coagulation protein plasminogen were altered between the control and PE group 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 to PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters with one of the clusters presenting the highest ratio cases:controls (P < 0.01) and associated with a higher concentration of smaller LDL cholesterol particles. Conclusions: Our findings indicate that the lipidome and proteome of subjects who report PEs at age 18 is already altered at age 12 indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting cross-talk between these LPCs, PCs and coagulation and complement proteins.
Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalBiological Psychiatry
Volume86
Issue number1
Early online date30 Jan 2019
DOIs
Publication statusPublished - 1 Jul 2019

Keywords

  • ALSPAC
  • Early life
  • Integration
  • Lipidomics
  • Proteomics
  • Psychotic episode

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Projects

    NIHR BRC Mental Health

    Gunnell, D. J.

    1/04/1731/03/22

    Project: Research, Parent

    Cite this

    Madrid-Gambin, F., Föcking, M., Sabherwal, S., Heurich, M., English, J., O'Gorman, A., Suvitaival, T., Ahonen, L., Cannon, M., Lewis, G., Mattila, I., Scaife, C., Madden, S., Hyotylainen, T., Oresic, M., Zammit, S., Cagney, G., Cotter, D. R., & Brennan, L. (2019). 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, 86(1), 25-34. https://doi.org/10.1016/j.biopsych.2019.01.018