Congruency and phenotypic plasticity of immune and nervous systems in children with autism spectrum disorders compared to schizophrenia spectrum disorders”, Medical Immunology (Russia)
Authors: Burmistrova A. L. , Filippova Yuliya Yu. 
Published: August 2020

According to new views on communication ways and principles in the main regulatory systems of the body, i.e., immune and neuroendocrine, there is a risk for disintegration of pathways and structures in these systems which may underlie disorders such as autism-spectrum disorders (ASD) and schizophreniaspectrum disorders (SSD). Both disorders are classified as neurodevelopmental disorders, with unclear etiology and partially overlapping pathophysiological developmental mechanisms. Diagnosis of ASD and SSD is based on patterns of clinical symptoms/syndromes that demonstrate high heterogeneity and similarity. Therefore, it is very important to find the ways of discerning children with ASD from those with SSD. Our aim was to identify peripheral activity indexes for immune and neuroendocrine systems, and their integration for usage as information hubs of congruency and phenotypic plasticity of these systems in children with ASD, as compared to SSD patients. The levels of 14 indexes of the immune and neuroendocrine systems in blood plasma were determined in 82 children with ASD, 9 children with SSD and 45 children with typical neurodevelopment (TD). To assess peripheral activity of the immune and neuroendocrine systems and their relationships, we applied a multivariate exploratory analysis using a method of nonlinear principal components. The following results were obtained: (1) absence of differences in proinflammatory cytokines between ASD and TD children; (2) patients with SSD have significantly higher values of IL-6 and IFNγ, and lower values of IL-1β, TNFα and IL-10 in blood plasma compared to children with ASD and TRD; (3) the level of neurohormones in children with ASD is in accordance with physiological reference values. The children with SSD have lower levels of epynephrine and dopamine compared to ASD and TD, respectively; (4) integration degree of regulatory systems assessed by principal component analysis has shown the following: (4.1) TD children have strong correlations within each of the systems and between them, thus showing their communicative abilities and plasticity, characteristic of normal values; (4.2) In SSD children, minimal numbers of strong relations were demonstrated within the cytokine system; (4.3) The children with ASD exhibited two clusters: one of them had a complete similarity with TDC, in terms of tension and assortment of immune and neuroendocrine indices; the other one presented low coupling between the parameters of regulatory systems, similar to the children with SSD; (4.4) Analysis of peripheral indices of cytokine and neuroendocrine systems for clusters 1 and 2 in children with ASD compared to children with SSD and TD demonstrated that, in children with ASD of cluster 1, the indices did not differ from TDC, except of epinephrine, ACTH, kynurenine, and tryptophan. In the children with ASD of cluster 2, the values of the indices are equal to children with SSD, except of dopamine and tryptophan. Thus, we have shown phenomenon of transdiagnostic clustering, i.e., allocation of two clusters among ASD children. One of them is similar to levels of indices and connections between the immune and neuroendocrine systems with TD, and another cluster is similar to SSD children. Therefore, they could be potentially useful as diagnostic criteria when discriminating the two disorders.