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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
Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.ORCID iD: 0000-0001-9333-0014
Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom.ORCID iD: 0000-0003-0105-2702
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2019 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 86, no 1, p. 25-34Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 86, no 1, p. 25-34
Keywords [en]
ALSPAC, Early life, Integration, Lipidomics, Proteomics, Psychotic episode
National Category
Neurology Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-75212DOI: 10.1016/j.biopsych.2019.01.018ISI: 000472860900007PubMedID: 30878195Scopus ID: 2-s2.0-85062721715OAI: oai:DiVA.org:oru-75212DiVA, id: diva2:1339202
Funder
Wellcome trust, 102215/2/13/2
Note

Funding Agencies:Health Research Board  HRA-POR-2013-282  HRBCSA2012/8 

European Research Council  647783  724809 

European Union FP7 collaborative project METSY  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  

UK Medical Research Council  102215/2/13/2 

Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved

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Hyötyläinen, TuuliaOresic, Matej

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