Cytokine-neuroendocrine peripheral signature in the context of the “accelerated ageing” phenomenon in autism spectrum and schizophrenia spectrum disorders

Currently, differentiation between autism spectrum disorders and schizophrenia spectrum disorders in children is a difficult task, because it relies mainly on behavioral and symptomatic characteristics, since these disorders are highly similar. We have previously demonstrated that peripheral indexes of immune and neuroendocrine systems, which we combined into cytokine-neuroendocrine signature, may reflect distinct clinical phenotypes of autism and schizophrenia spectrum disorders. Moreover, a number of researchers discovered the “accelerated ageing” phenomenon in the persons with schizophrenia, which includes deficiencies of cognitive functions and performance as the main symptoms. Here we carried out a search for biological markers of the “accelerated ageing” phenomenon in children with autistic conditions and schizophrenia spectrum disorders. Our aim was to assess the opportunity of applying the cytokine-neuroendocrine signature as biological evidence of “accelerated ageing” phenomenon in children with autism and schizophrenia spectrum disorders, which could be potentially useful for differential diagnosis of these disorders.

Thirteen parameters of the cytokine-neuroendocrine signature were assessed in blood plasma using ELISA method in 82 children with autism, 9 children with schizophrenia, 45 normally developing children, 25 subjects in their reproductive age, and 39 elderly persons: cytokines (IL-6, IL- 1β, IFNγ, TNFα, IL-10, IL-4) and neurohormones (oxytocin, dopamine, adrenaline, noradrenaline, adrenocorticotropic hormone, cortisol, and serotonin). The nonlinear principal component analysis (CATPCA algorithm) was used to assess the variants of cytokine-neuroendocrine signature for different diagnostic categories, i.e., “autism spectrum disorders”, “schizophrenia spectrum disorders”, and “healthy ageing”.

The “healthy ageing” variant of cytokine-neuroendocrine signature presented a classic phenomenon, referred to as immune senescence presented by pro-inflammatory age-related cytokines — IL-6, IL- 1β, IFNγ. Only the “schizophrenia spectrum disorders” variant of the cytokine-neuroendocrine signature, unlike all the other signature variants, demonstrated high-level similarity with the “healthy ageing” variant (differing in 2 out of 13 indexes): lower levels of IL- 1β and IFNγ, at the same level of IL-6 “gerontological cytokine” index.

Evaluation of the cytokine-neuroendocrine signature can be used for differentiation between autistic disorders and schizophrenia spectrum disorders, including predictive diagnostics in children with autism, thus enabling group selection of children at risk for later conversion to schizophrenia.