Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort

A O'Gorman,M Cannon,I Mattila,S Zammit,L Ahonen,T Hyotylainen,G Lewis,T Suvitaival,H M Roche,M Oresic,L Brennan,D R Cotter

doi:10.1038/tp.2017.211

Abstract

The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18:1), LPC(18:2), LPC(20:3); phosphatidlycholines (PCs) PC(32:2; PC(34:2), PC(36:4), PC(0-34-3) and sphingomyelin (SM) SM(d18:1/24:0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD.

Highlights

Psychotic disorders (PD) are among the most severe and debilitating medical diseases, with schizophrenia being the most common, affecting ~ 0.5–1% of the global population.[1]
Clear patterns are not seen for the PCs and TGs, the figure does highlight that the PCs are elevated in the PD group and TGs are downregulated, so for those with a lower number of carbon double bonds
Our findings indicate that the lipidome is altered between subjects with PD compared to subjects who do not experience any Psychotic experiences (PE), at the age of 11, giving promise to the potential of an early biomarker signature of PD

Summary

Introduction

Psychotic disorders (PD) are among the most severe and debilitating medical diseases, with schizophrenia being the most common, affecting ~ 0.5–1% of the global population.[1]. Strong evidence supports early intervention as a means to alleviate and improve therapeutic outcome for individuals.[4,5] Owing to the multifactorial complexity of PD,[2,6] the identification of a disease signature and molecular biomarker(s) sensitive to the underlying pathogenic factors would be of great importance to assist in early detection and diagnosis[7] and to understand the mechanisms underlying the disease process, which has yet to be fully elucidated.[8]

Objectives

Methods

Results

Conclusion