Variation in the Content of Three Tandem Repeats (Ribosomal, Satellite III and Telomeric) in the DNA of Blood Leukocytes of Children with Mental Disorders, as a Potential Marker for the Differential Diagnosis of Childhood Schizophrenia and Autism Spectrum Disorders

Background: a problematic issue in child psychiatry is the differential diagnosis of early childhood schizophrenia and autism spectrum disorders (ASD). Previously, the authors showed that the genomes of children with schizophrenia, like the genomes of adult patients, contain more copies of ribosomal genes than the genomes of children with ASD. For adult patients with schizophrenia, a decrease in the content of satellite III repeat (1q12) in blood leukocytes and a decrease in the average telomere length were also shown. The aim of study was an analysis of the content of three genome repeats (ribosomal, satellite III and telomeric) in DNA samples of blood leukocytes of children with endogenous mental disorders in order to search for a genetic marker that allows for differential diagnosis of early childhood schizophrenia and ASD. Patients, Control groups and Methods: blood samples from 136 patients with ASD (F84.0 and F84.1 according to ICD-10) and childhood-onset schizophrenia (F20.8xx3 according to ICD-10) were obtained from the Department of Child Psychiatry of the Mental Health Research Centre. DNA samples from the healthy control group (93 children and 78 adults) were taken from the collection of samples of Research Centre for Medical Genetics. The selection of patients was carried out using the clinical-psychopathological method. DNA was isolated by extraction with organic solvents. The content of three repeats in DNA was carried out using non-radioactive quantitative hybridization. Data were analyzed using the package “StatPlus2007 Professional software”, “MedCalc”, Excel Microsoft Office, “StatGraph”. Results: patients DNA samples from children with schizophrenia contain more ribosomal genes and less satellite III than DNA from children with ASD and DNA from healthy children (p < 0.001, U test). DNA samples of patients with ASD and schizophrenia contain fewer telomeric repeats than healthy child controls (p < 10⁻¹⁰). The Ksz indicator, equal to the ratio R2/(S·T), which takes into account the increased content of the ribosomal repeat and the reduced content of the satellite and telomeric repeat in the DNA of children diagnosed with childhood schizophrenia, showed the maximum differences between the group of children with schizophrenia and the group of children with ASD (p < 10⁻¹¹, U test; ROC analysis: AUC = 0.88, p < 0.001). Conclusion: the Ksz indicator can potentially be used in practice to confirm the diagnosis of schizophrenia in children with mental pathology.

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