Reduced Exploration and Stereotyped Behavior †MyAssignmenthelp

Question: Discuss about the Reduced Exploration and Stereotyped Behavior. Answer: Introduction Autism spectrum disorder (ASD) is an umbrella term that encompasses a group of neurodevelopmental disorders, characterized by developmental delay, abnormalities in langugage comprehension, social interaction, reciprocity, communication, and repetitive stereotypical behaviors and interests [1]. Although previoius studies provided evidences for the underlying genetic, prenatal, early postnatal, and biochemical pathways that are responsible for the disorder, the etiology and pathogenesis are still unclear. Epidemiological studies suggest that there is not a single reason that leads to the occurrence of ASD. Mulitfactorial conditions (genetic and environmental) contribute to the development of autism [2,3]. Recent studies have focused on the possible role of cerebellar atrophy and loss of Purkinje cells in these neuropsychiatric disorders [4-6]. The most widely known abnormalities associated with ASD are atrophy of the cerebellum and selective loss of Purkinje cells [7]. ASD appears to d ecrease the volume of neocerebellar vermis and results in loss of Purkinje cells in the cerebellar hemispheres. These factors are thought to contribute to impaired attention, vigilance, and sensorial processes in children with ASD [8-10]. Developmental abnormalities and damage to the cerebellum result in impaired cognitive functions, poor verbal skills and increased stereotypical behaviors [11-12]. These findings support the idea that abnormal density of Purkinje cells could contribute to development of autism phenotype [13]. Attention Deficit Hyperactivity Disorder (ADHD) is another common child neuropsychiatric disorder that persisits into adulthood. A meta-analysis study showed a frequency of 5-29% among children [14]. ADHD and ASD have similar biological features and are likely to be found together [15-16]. Although, the etiology of ADHD is unclear, both neurobiological and psychosocial factors are thought to play a role. Recent studies have mostly evaluated cerebellar atrophy and loss of Purkinje cells [17]. Cerebellar abnormalities are consistently found in ADHD structural neuroimaging studies [18,19]. Additionally, many studies have reported impaired developmental differentiation and decreased cerebellar volume among ADHD children [20-23]. Studies that investigated the pathophysiology of both ASD and ADHD pointed out common structural differences in cerebellum [8,9,18,19]. However, previous studies failed to compare the disorders in terms of cerebellar degeneration. Presence of Anti-Yo antibodies i s the most common and well defined characteristic of cerebellar degeneration [24]. Additionally, distribution of glutamic acid decarboxylase (GAD) in the neuroendocrine tissues and antibodies against GAD act on the cerebellar pathways [25]. These findings highlight the need to (1) compare anti-Yo and anti-GAD serum levels between children with ADHD, ASD, and healthy control group, and (2) investigate the association between antibody levels, sociodemographical features and symptom severity among children with ASD. A total of 119 Caucasian children aged 4 to 12 years of age, who were admitted to the Ankara Pediatric Hematology Oncology Training and Research Hospital between July 2015 and July 2016, were included in this study. The children were gender matched and belonged to the same grade level. They were also matched for their intelligent levels. The sample population consisted of 40 children diagnosed with ASD and 39 children diagnosed with ADHD, according to DSM-5 criteria. A stratified sampling method was used to select 40 healthy children belonging to the same age group from three different pre-school institutions and three primary schools. They formed the control group. Children with comorbid psychiatric disorders, chronic medical illnesses, mental retardation (intelligence quotient 70) and developmental delays were excluded from the study. Additionally, patients with pure ASD or ADHD were included in the appropriate groups. The parents and children were informed about the study. Verbal and written consent was obtained from the parents. The study was financed by the Ankara Pediatric Hematology Oncology Training and Research Hospital Scientific Research Support Commission. It followed the principles of the Declaration of Helsinki, and was approved by the Ethical Committee of Ankara Pediatric Hematology Oncology Training and Research Hospital. Researchers determined the socio-demographical features and clinical features of all participants. The children were assessed by child and adolescent psychiatrists. They were diagnosed with ADHD or ASD according to the DSM-5 criteria. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS PL) was applied to the clinical sample to evaluate the differential diagnosis of each symptom. The reliability and validity of K-SADS-PL was assessed by Gkler [26]. An assessment of the children aged between 4-6 years was done using the Denver-II (Denver Developmental Screening Test) or Stanford Binet test, to exclude developmental delays from consideration. The revised edition of Wechsler Intelligence Scale for Children was used to exclude mental retardation among the participants aged between 6-12 years. The Conners Parent Rating Scale-Revised Long Form (CPRS) and Conners Teacher Rating Scale-Revised Long Form (CTRS) were completed by pa rents and teachers of children diagnosed with ADHD. The Autism Behavior Checklist (ABC) and Aberrant Behavior Checklist (AbBC) were completed by parents of autistic children. Researchers applied the Childhood Autism Checklist Scale (CARS) to all participants with autism. The serum anti-Yo and anti-GAD levels were analysed from all participants via the Enzyme-Linked ImmunoSorbent Assay (ELISA) method, in a laboratory at the hospital. The method was used as a quantitative measurement to investigate the antigen-antibody relationship, and the activity of an enzyme bound to an anti-core antibody. Conners Parent Rating Scale-Revised Long Form (CPRS): It is an assessment tool used by parents to report behavioral problems and severity of ADHD symptoms in their children aged 3-17 years [27]. This four-point Likert scale consists of 80-items. The translation, validity and reliability of the Turkish version of the scale were done by Kaner [28]. Conners Teacher Rating Scale-Revised Long Form (CTRS): This scale is given to teachers to evaluate behavioral problems and ADHD symptom severity among their students aged between 3-17 years [27]. This four-point Likert scale consists of 59-items. The validity and reliability of the Turkish version was tested by Kaner [29]. Aberrant Behavior Checklist (AbBC): This scale is used to determine the severity of behavioral problems among children with autism. It is a five-point Likert scale consisting of 58 items that assists parents to score problematic behavior in their children [30,31]. Assessment of five different subgroups namely, irritability, lethargy, social withdrawal, stereotypies, and hyperactivity give different scores. Validity and reliability studies were done for the Turkish sample [32]. Childhood Autism Rating Scale (CARS): This autism behavior rating scale, which consists of 15-items and 14 domains, is mostly used by clinicians for diagnosing and determining autism severity. Each item is scored from 1 to 4 [33]. A minimum score of 30 is required to determine if a child is autistic [34]. Validity and reliability studies were completed for a Turkish sample [35]. The value of Cronbach coefficient was 0.95. Autism Behavior Checklist (ABC): This checklist was developed by Krug [36]. It consists of 57 items, placed in five different categories: sensory, relational, body and object use, language, social and self-help. It is used by clinicians to quantify behaviors associated with autism. Turkish reliability and validity studies had been conducted. High scores were reported for internal consistency and split-half reliability (.92) [37]. The cut-off point for the scale is 39. Preparation of the sample Anti-Yo: 5 cc of blood was kept at room temperature for 15 minutes and subjected to 4100 cycles of centrifugation for 5-10 minutes. The serum was studied using ELISA method, which is an analytical biochemistry assay, used to detect and quantify presence of a substance. The upper layer (serum) was tubed using a pipette. Anti-GAD: 5 cc of blood was kept at room temperature for 15 minutes and subjected to 4100 cycles of centrifugation for 5-10 minutes. ELISA method was used to study the serum. The method is biochemistry assay that detects and quantifies presence of a substance. The reference value was accepted to be Analysis was done using the SPSS 17.0 software package. The Kolmogorov-Smirnov (K-S) statistical test revealed the absence of any normal distribution between the variables. The Kruskal-Wallis test was used in combination with Bonferroni correction to compare the variables among ASD, ADHD and control groups. p The participants were divided into three groups based on their diagnosis: children with ADHD, children with ASD, and healthy children. No significant differences were observed among them with respect to their socio-demographical features (age, BMI of children and the age and education level of their parents), as shown in Table 1. (p .05). Anti-Yo levels and GAD levels were compared between the groups (Table 2). The median GAD levels were 293.4 pmol/L for ASD, 360.4 pmol/L for ADHD, and 311.2 pmol/L for healthy subjects respectively. No significant differences were observed between GAD levels among the groups. Median anti-Yo levels were 2.1 pmol/L for ASD, 2.9 pmol/L for ADHD, and 1.6 pmol/L for healthy subjects. Significant differences were detected in proportion of antibodies between the three groups (X2=12.162, df=2, p=0.002). Dichotomic analysis using a Mann-Whitney U test revealed that comparison between children with ADHD and healthy subjects resulted in a significant anti-Yo ra tio (U=460, 500, z=-3.133, p=0.002). The anti-Yo levels of ADHD group were higher than corresponding levels among healthy children. A correlation analysis was performed to evaluate the association between anti-Yo and GAD levels with age, ABC and AbBC scores. Poor positive correlation was found between children age and GAD levels (Spearman rho=0.187, p=0.042). However, no correlation was found between groups (autism: r=0.105, p=0.519; ADHD: r=0.285, p=0.079; healthy subjects: r=0.253, p=0116). A negative correlation was observed between children age and ABC scores (Spearman rho=-0.475, p=0.002) as well as with CARS scores (r=-0.437, p=0.005). Positive correlation was also observed between AbBC and CARS scores among children with ASD (r=0.353, p=0.001) (Table 3). The study investigated the levels of cerebellar antibodies among children diagnosed with ASD or ADHD. According to the findings, no significant differences in antibody levels were observed among the 2 groups. However, children with ADHD reported significantly higher levels of Purkinje cell antibodies, when compared to the healthy subjects. These results supported the possible role of cerebellar damage in ADHD etiology. Most recent studies on ADHD have established association of the disease with abnormalities in Purkinje cells, reduced cerebellar volume, and developmental differences [20-23]. Studies have also been conducted to investigate the relationship between anti-Yo antibodies and ADHD. Passarelli and colleagues investigated the relationship between ADHD and cerebellar antibodies and pointed out a possible association between anti-Yo antibodies and ADHD combined subtype [17]. In addition, Donfrancesco and his colleagues compared 58 children diagnosed with ADHD with 36 healthy ch ildren and reported higher levels of antineural antibodies in the ADHD group [38]. High levels of cerebellar antibodies among ADHD subjects in this study showed consistency with earlier findings [17,38]. Structural imaging studies on autism have reported a decrease in number of cerebellar Purkinje cells and differences in cerebellar volume [39,40]. The potential role of immune system in ASD etiology have been consistently supported by evidences that demonstrated functioining of autoantibodies against brain-specific antigens among autistic children [41,42]. Although, higher levels of antibodies were found in the ASD group when compared to controls in the present study, no significant difference was observed. Therefore, further investigation is required to evaluate the association between cerebellar antibodies and ASD. However, the results did not provide definitive support for excluding the association and etiopathogenetic connection between cerebellar degeneration and ASD. The study was a first-in-human study that investigated the presence of cerebellar antibodies in ADHD and ASD, and compared it to a control group. The findings point to the fact that cerebellar degeneration has a po ssible role in ADHD. However, the study had several limitations. Firstly, the sample groups were relatively small, and this might have affected the levels of significant differences among the groups. Secondly, the study did not include any long term follow-up period. In the study, a poor positive correlation was observed between the ages of the children and their GAD levels. Therefore, a change in the levels of antibodies might occur as the children grew older, independent of a disease. Furthermore, the values were momentary. Thus, presence of fluctuations in antibody levels could not be assessed. Conclusion In conclusion, the study pointed out an association between the presence of cerebellar antibodies and ADHD. There is a need to increase focus on common neuropsychiatric disorders such as ADHD and ASD, in order to develop effective treatment approaches. In this context, the study forms an important foundation for prenatal and postnatal diagnosis and therapeutic interventions. It may act as a pioneer of further research in this field. 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