الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
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Abstract
Autism is a set of complicated neurodevelopmental problems of unidentified etiology that manifests with problems with social communication, verbal communication and behavior deficits as stereotype activities and repetitive actions. The majority of cases of traditional autism found with failure to develop normal, social or language skills, which is called early onset autism. Nevertheless, a group of children with autistic attributes grow normally till about 18 to 24 months of age after which they show neuro-regression. This is called as regressive autism.
Symptoms or signs commonly begins before three years of age and may lead to delays or troubles in many different skills which develop from childhood to adulthood. However, the age of diagnosis is around 6 years. Autism Spectrum Disorder (ASD) is assessed by a medical psychologist by DSM-IV criteria that can be quite challenging because of complex phenotypes.
Therefore, early diagnosis is required thus ideal biomarkers is being investigated. Different patients with autism have various spectrum of mild to severe autistic characteristics and clinical symptoms. So the expression “Autism Spectrum Disorder” is frequently used by doctors.
Dopamine and serotonin are among the neurotransmitters which were suspected to be altered in autism. Dopamine is suspected to be involved in repetitive behaviors, deficits in executive functions
and altered motor activities in autism. It is also related to immune system functions which were reported to be different in autism. Additionally, serotonin system was implicated in immune system, response speed control, cognitive functioning and social abilities which all are essential for language development. The dopamine and serotonin systems were reported to be influenced by the brain derived neurotrophic factor (BDNF).
Moreover, BDNF has a role in neuronal connectivity especially in hippocampus and hypothalamus and peripheral sensory nerves. Hence, investigating the possible relations between these measures and each other and especially those with delayed language development would reveal information about the pathogenesis of autism.
In that way, this research aims to measure the blood levels of dopamine, brain derived neurotrophic factor and serotonin in a group of Egyptian autistic children compared to healthy control children matched for age and sex with the autistic children and to investigate the relation between these measures and each other in the autistic group.
The study included 40 children with autism in group I and 20 healthy control children in group II with the same socioeconomic class. group I participants were attending the learning disability research clinic in Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt.
The children in group I were 27 males and 13 females and their age ranged from 3.1 to 11 years. In group II, they were 12 males and 8 females with age range 3.5-9.1. Children with autism were diagnosed to have an autistic disorder and communication disorder according to the criteria of diagnostic and statistical manual of mental disorders, fourth edition, text revision.
The dopamine and serotonin levels were estimated by high- performance liquid-chromatography (HPLC), while serum BDNF concentration was measured by sandwich ELISA method in the medical biochemistry department, medical research division, National research Centre.
Comparison between the groups shown that the dopamine level in children with autism was less than the level in the control group. The BDNF level in the autism group was more than that in the control group with statistically significant difference for both measures. The serotonin level did not show a statistically significant difference between the groups despite being less in the autism group.
Comparative analysis for the plasma levels of dopamine, serotonin and BDNF between autistic and healthy control groups showed high significant difference was observed for the dopamine
level in autistic children compared with healthy children (p≤0.001). Also results showed that there is an increase in the serum level of BDNF in autistic children compared to healthy group, and a significant statistical difference was achieved between both groups
(p≤0.001). On the other side, no significant difference was detected for the plasma level of serotonin between autistic and healthy children
(p≥0.05).
In addition, comparative analysis for the expression levels of dopamine, serotonin, and BDNF between autistic children with different language impairment score showed a high significant association was found between the serum level of BDNF and severity of language impairment score (p<0.001). However, no significant difference was reached for plasma level of dopamine, serotonin with severity of language impairment score.
Receiving operating characteristics curve was performed and it revealed an optimum cut-off value (0.2) for dopamine with sensitivity 90% and specificity 70%, while cut-off value (0.3) for serotonin with sensitivity 70% and specificity 80%. Also, BDNF revealed an optimum cut-off value (85.5) with sensitivity 88% and specificity 85%. Accuracy of dopamine, serotonin and BDNF were 83.5%, 65% and 87% respectively. Therefore, the three plasma biomarkers are significantly related with autism, and thus, they could be considered as a good diagnostic biomarker in autistic patients.
Correlation analysis between the biochemical measures and each other revealed significant positive correlation between the levels of dopamine and brain derived neurotrophic factor.
Conclusion
In conclusion, the present study demonstrated an impaired expression of dopamine, serotonin and BDNF in autistic children compared to control subjects, this would be suspected to be related to etiological or exaggerating factors for the deficits in such children. In addition, the three investigated neurotransmitters showed a predictive potential in autism with good suitable sensitivity and specificity. Furthermore, BDNF, dopamine and serotonin level was significantly correlated to the severity of autism based on CARS assessment.
The limitation of this study was related to small sample size with heterogeneity in clinical presentation of the selected subjects, therefore, we recommend to apply a serial measurement of plasma dopamine, serotonin and BDNF in autistic patients in order to predict the disease progression and predict the response to treatment, moreover, to conduct the study on large scale of patients with respect to minimize the patient’s variables in order to maintain sample homogeneity.