Otizm Spektrum Bozukluğu’nda Nöronal Hasar Proteinleri ve Matriks Metalloproteinazların Otistik Regresyon ile İlişkisinin İncelenmesi

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by disruptions of social communication and interaction, restricted interests, and stereotyped behaviors. The time of the beginning and clinical course shows heterogeneity in the disorder. Some of the patients lose their developmental steps after having a normal developmental period and this condition is known as “autistic regression”. The etiopathology of ASD and autistic regression is still unclear. Still, both genetic and environmental factors influence the structural and functional development of the brain in the early years of life, and this situation is responsible for the emergence of autistic symptoms. Immune system problems, changes in blood-brain barrier permeability, and neuronal/astroglial damage are associated with the etiopathogenesis of ASD and autistic regression. It is thought that these changes may affect many parts of the brain and cause changes in cognitive and behavioral functions, which paves the way for the development of ASD as well as many neurological and psychiatric diseases. 50 children with ASD between the ages of 4-10 and 30 healthy children without any chronic disease were included in this study. K-SADS-PL psychiatric diagnosis interview, Childhood Autism Rating Scale (CARS), and a semi-structured interview in order to evaluate regression administered to all participants. Regression was defined as loss of acquired skills in language and/or non-linguistic social/communicative areas. Parents were asked to fill in the Aberrant Behavior Checklist (ABC), Autism Behavior Checklist (AuBC), Revised Conners Parent Rating Scale Revised Short Form (CPRS-RS) and Social Responsiveness Scale (SRS). Between ASD and control group, serum levels of Matrix Metalloproteinase-9 (MMP-9), glial fibrillary acid protein (GFAP), S100 calcium binding protein B (S100B), ubiquitin carboxyl terminal hydrolase-L1 (UCHL-1) and neurofilament heavy chain (NF-H) were compared; the changes in their level in the ASD group in terms of the presence of regression, clinical features, and symptom severity were examined. In this study, based on the hypothesis that inflammation may cause increased permeability in the blood- brain barrier and neuronal/astroglial damage; it was hypothesized that MMP-9 and neuronal/astroglial injury marker proteins would be higher in the ASD group than in the control group and in the ASD group in those with regression than in those without. As a result of the study, no difference was found between the ASD and control groups in terms of sociodemographic characteristics. In the ASD group, the presence of physical disease in the mother during pregnancy, drug use, and perinatal complication rates were found to be statistically significantly higher. There was no significant difference in serum levels of neuronal/astroglial injury proteins and MMP-9 between the ASD and control groups. The ASD group was examined in two groups according to the presence of regression; there was no statistically significant difference between the two groups in terms of sociodemographic variables, clinical features, CARS, ABC, AuBC, CPRS-RS, and SRS scores. In addition, no significant difference was found between neuronal/astroglial damage proteins and MMP-9 serum levels between regression and non-regression groups. Participants who showed regression were divided into two groups according to the onset of regression as those with regression following a previously normal development and those with worsening pre-existing autistic features, these groups were compared in terms of sociodemographic and clinical variables and biochemical variables. It was found that the group with worsening pre-existing autistic features started to form sentences later and scored higher on the ABC inappropriate speech subscale than those who showed regression following normal development. There was no statistically significant difference between the two groups in terms of other variables. As a result, it was determined that those with and without regression in the ASD group were similar in terms of sociodemographic, clinical, and biochemical variables. The findings obtained in this study suggested that it is necessary to question whether the peripheral circulation can represent changes in central nervous system and to review the existence of autistic regression as a separate entity in ASD in terms of clinical features and etiopathogenesis.