Search In this Thesis
   Search In this Thesis  
العنوان
Study of Attention Deficit Hyperactivity Disorder in a
Sample of Children and the Role of DAT1 Gene
Polymorphism as a Biomarker /
المؤلف
Nagi, Dina Abdallah.
هيئة الاعداد
باحث / دينا عبد الله ناجي
مشرف / هويـــــدا الجبالــــــي
مناقش / هيام كمال نظيف
مناقش / ماجد عطا الوكيل
تاريخ النشر
2023.
عدد الصفحات
144 P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
طب الأطفال ، الفترة المحيطة بالولادة وصحة الطفل
تاريخ الإجازة
1/1/2023
مكان الإجازة
جامعة عين شمس - معهد الطفولة - قسم الدراسات الطبية للأطفال
الفهرس
Only 14 pages are availabe for public view

from 144

from 144

Abstract

Attention deficit hyperactivity disorder (ADHD) is characterized by difficulty with attention, hyperactivity, and impulsivity. ADHD is divided into three subtypes (predominantly inattentive type ADHD, predominantly hyperactive-impulsive type ADHD combined type ADHD) were established in year 2000 in DSM-IV.
Attention-deficit-hyperactivity disorder (ADHD) is one of the most frequently diagnosed psychiatric disorders in children with an estimated worldwide prevalence of 5.3–8.7%. (ADHD) is an early onset and highly heritable neuropsychiatric disorder persisting into adulthood in up to 60% of the cases. Its prevalence was estimated to be 5.29% in school-aged children and 2.5% in the adult population.
The etiology and pathogenesis of attention-deficit/ hyperactivity disorder (ADHD) are unclear, and a more valid diagnosis would certainly be welcomed.
The subjective nature of the diagnostic criteria may lead to misdiagnosis with other neurodevelopmental disorders (Daley, 2004). Therefore, objective markers of the disease are required to validate diagnosis, prognosis and assessment of response to pharmacological interventions. Genetic and biochemical markers have been suggested to help diagnose ADHD in childhood.
DAT1 is one of the most studied genes in the etiology of ADHD. It regulated dopamine transport in the synaptic space through dopamine reuptake into the presynaptic neuron. Dopaminergic system imbalance has been implicated in the pathogenesis of many neurological disorders, including ADHD, schizophrenia, bipolar disorder, and Parkinsonism.
The DAT gene (DAT1, SLC6A3) is located on chromosome 5p15.3 and contains a 40 bp variable number tandem repeat (VNTR) polymorphism in the 3’-untranslated region. The 9-repeat and the 10-repeat alleles are the most frequent. Many studies supported the positive association of the 10/10 genotype ADHD. Yet, many other studies provide negative results. Further analysis was recommended by the authors to achieve a robust conclusion. Therefore, this study aimed to study ADHD and to test the possible association between the 40-bp VNTR in the 3′-UTR regions of DAT1 and ADHD disease in a sample of Egyptian children.
The study included 60 patients with ADHD and 60 normal control subjects between 6 and 17 years of age. All patients were subjected to psychometric assessment using an Arabic version of the 48-item Conners’ Parent Rating Scale (CPRS-48). An Arabic translation of the Childhood Behavioral Checklist (CBCL) was used to detect behavioral and emotional problems in the included children. Genomic DNA was extracted to detect the 40-bp VNTR in the 3′-UTR region of DAT1.
ADHD type was combined in 83.3% of the cases, predominantly hyperactive-impulsive in 10.0%, and predominantly inattentive disease in 6.7%.
According to Conners’ rating scale, 81.7% had scores within the clinical range of the 10-item hyperactivity index (HI) subscale. Also 63.3% of the cases had clinical range scores of learning problems subscale followed by Conduct Disorder in 20.0%. On the contrary, the psychosomatic and anxiety subscales showed normal ranges in most cases.
In the current study, the main aim of using CBCL was to screen for comorbid psychopathology in children with ADHD. CBCL scores showed 73.3% to have scores within the clinical range of ADHD subscale. The main comorbidity found in the DSM-Oriented scores was clinical range scores of conduct problems in 61.7% of the patients. Also, affective, and oppositional defiant problems (ODD) were observed in nearly half of the patients.
The syndrome scale scores of the CBCL revealed comparable results. It showed that 76.7% had scores within the clinical range of the attentive problems. Also, 60% of the patients had clinical range scores of aggressive behaviors. 50% of the patients showed rule breaking behavior, while 46.7% showed social problems.
More than half of the ADHD patients showed clinical range in the activities score of the CBCL competence scales.
This study demonstrated no significant difference between the ADHD and control groups (p=0.104) in DAT1 VNTR. The 10R/10R genotype was the predominant one in the control group (58.3%) and was found in 40% of the ADHD children. The 10R/10R genotype was more common in the hyperactive/impulsive and inattentive compared to the combined ADHD subtype (p=0.1)
Conclusion:
Our results showed that the difference between the ADHD and control groups in the DAT1 VNTR genotype was statistically not significant. The 10R/10R genotype was the predominant one in the control group (58.3%) and was found in 40% of the ADHD children.
In our study DAT1 polymorphism was not proven to have a role as a biomarker in diagnosis of ADHD