Metabolome signature of autism in the human prefrontal cortex

Ilia Kurochkin,Tobias Halene,Qian Li,Vita Stepanova,Ekaterina Khrameeva,Lothar Willmitzer,Patrick Giavalisco,Polina Shichkova,Anna Tkachev,Dmitry Zubkov,Anna Vanyushkina,Elena Stekolshchikova,Schahram Akbarian,Philipp Khaitovich

doi:10.1038/s42003-019-0485-4

Abstract

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with yet incompletely uncovered molecular determinants. Alterations in the abundance of low molecular weight compounds (metabolites) in ASD could add to our understanding of the disease. Indeed, such alterations take place in the urine, plasma and cerebellum of ASD individuals. In this work, we investigated mass-spectrometric signal intensities of 1,366 metabolites in the prefrontal cortex grey matter of 32 ASD and 40 control individuals. 15% of these metabolites showed significantly different intensities in ASD and clustered in 16 metabolic pathways. Of them, ten pathways were altered in urine and blood of ASD individuals (Fisher test, p < 0.05), opening an opportunity for the design of new diagnostic instruments. Furthermore, metabolic measurements conducted in 40 chimpanzees and 40 macaques showed an excess of metabolite intensity differences unique to humans, supporting the hypothesized disruption of evolutionary novel cortical mechanisms in ASD.

Highlights

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with yet incompletely uncovered molecular determinants
Changes in the purine metabolism pathway, pyrimidine metabolism pathway and changes in several pathways involved in the metabolism of tyrosine, asparagine, tryptophan and arginine were further identified in the urine of 30 ASD individuals using a combination of the nuclear magnetic resonance (NMR) and liquid chromatography coupled with mass spectrometry (LC–MS) approaches were reported by Dim et al.[19]
The first study investigating metabolite concentration differences in blood identified changes associated with mitochondrial dysfunction, as well as various metabolic pathway changes, such as a disruption in the tricarboxylic acid (TCA) cycle in the plasma samples of 52 children diagnosed with ASD using five mass spectrometry-based methods were reported by West et al.[23]

Summary

Introduction

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with yet incompletely uncovered molecular determinants. The first study investigating metabolite concentration differences in blood identified changes associated with mitochondrial dysfunction, as well as various metabolic pathway changes, such as a disruption in the tricarboxylic acid (TCA) cycle in the plasma samples of 52 children diagnosed with ASD using five mass spectrometry-based methods were reported by West et al.[23]. The only study conducted in the brain, by Graham et al.[25], identified concentration differences of 37 metabolites in the cerebellum of 11 ASD individuals and 11 controls using LC–MS. These differences were not enriched in any biological pathway[25]

Methods

Results

Conclusion