An excess of metabolite intensity differences unique to the brains of individuals with autism spectrum disorder has been found by scientists from the Skoltech Center for Neurobiology and Brain Restoration (CNBR), the Icahn School of Medicine at Mount Sinai (ISMMS, New York, USA), the Max Planck Institute in Potsdam, and the Cologne Institute (Germany).

The findings provide insight into the molecular processes that take place in the brain of autistic individuals.

Autism spectrum disorder (ASD) is a range of nervous system disorders that manifest themselves primarily through impairment of cognitive functions and social communication and interaction abilities. The underlying molecular mechanisms of ASD are still poorly understood.


The researchers studied metabolites, tiny molecules that form in the prefrontal cortex as a result of biochemical reactions in the human system, both in neurotypical people and individuals with ASD, and compared the results to the tests made for the same brain region in macaques and chimpanzees. The study was performed using mass spectrometry, a highly accurate and sensitive analytical technique, that helped register and measure the concentrations of 1,366 different molecules clustered in 16 metabolic pathways.

Using blood and urine samples from healthy people as a reference, the scientists discovered multiple differences in metabolite concentrations between autistic and healthy humans.

[caption id=“attachment_99250” align=“aligncenter” width=“680”]Characterization of metabolite intensity differences identified in the prefrontal cortex of ASD individuals. Characterization of metabolite intensity differences identified in the prefrontal cortex of ASD individuals.
Credit: Ilia Kurochkin, Et al, CC-BY[/caption]

Interestingly, most of those differences are known to be related to the metabolic pathways that were found earlier in the urine and blood samples taken from autistic individuals.

When comparing the brain metabolites in humans and other mammals, including chimpanzees and macaques, it becomes clear that a marked difference between healthy and autistic individuals is observed in those metabolic pathways which are affected by multiple human-specific evolutionary changes, which leads the scientists to believe that autism tends to disrupt evolutionarily novel mechanisms.

Earlier Studies

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.

In a more recent study, Wang et al. identified the concentration differences of 17 metabolites in the blood plasma of 73 ASD individuals. Of them, 11 metabolites, including sphingosine 1-phosphate and docosahexaenoic acid, were validated in an independent cohort24.

The only study conducted in the brain, by Graham et al., 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 pathway25.

“Some earlier studies clearly pointed to the differences in metabolite concentrations in urine and blood, but fell short of establishing a possible connection to the brain processes. Our team focused on the prefrontal cortex, where we identified a host of ASD-specific metabolic features. We compared metabolites in the human brain to those in the brains of chimpanzees and macaques and found that ASD affects evolutionarily novel metabolic pathways,"

said Ekaterina Khrameeva, assistant Professor at Skoltech.

The work was supported by the National Key R&D Program of China; the National Natural Science Foundation of China; the National One Thousand Foreign Experts Plan; the Russian Science Foundation; and the Skoltech Systems Biology Fellowship.

Ilia Kurochkin, Ekaterina Khrameeva, Anna Tkachev, Vita Stepanova, Anna Vanyushkina, Elena Stekolshchikova, Qian Li, Dmitry Zubkov, Polina Shichkova, Tobias Halene, Lothar Willmitzer, Patrick Giavalisco, Schahram Akbarian & Philipp Khaitovich Metabolome signature of autism in the human prefrontal cortex Communications Biology, volume 2, Article number: 234 (2019)

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