Dikkat Eksikliği Hiperaktivite Bozukluğu Alt Tiplerinde ve Tedaviye Dirençli Olgularda Genetik Farklılıklar

Abstract

This research explored the relationship of ADRA2A and COMT gene polymorphisms among ADHD phenotypes such as subtypes of ADHD and other homogeneous groups like treatment-resistant cases and patients with higher psychiatric symptom severity. For this purpose, 121 ADHD patients aged between 6 and 18 years old were recruited from children admitted to Hacettepe University Child and Adolescent Psychiatry Department. Children having comorbid disorders such as mental retardation, anxiety disorders, mood disorders, autism spectrum disorders, psychosis and substance use disorders were excluded. The patients' ADHD subtypes were confirmed with the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). All of these patients were genotyped for these two single nucleotide polymorphisms from peripheral venous blood collected in EDTA tubes. The patients' families were assessed for familial functioning with the McMaster Family Assessment Device and the parents'ADHD symptoms were scanned with the Wender Utah Rating Scale. While the patients' symptoms were determined by the Conners' Parent and Teacher Rating Scales, symptom severity was categorized with Clinical Global Impression Scale and functioning with Global Assesment of Functioning Scale. Patients were assessed in a naturalistic fashion for methylphenidate response with these scales, Continuous Performance and Trail Making tests after methylphenidate treatment. Genetic analyzes took place in Hacettepe University Medical Genetics Department by using PCR/RFLP protocols. The control group was composed of banked DNAs in Hacettepe University Medical Genetics Department from a population with similar gender distribution. In univariate analyses, COMT and ADRA2A SNPs were not found associated with homogenous patient groups. Also, there wasn't any significant distribution difference between control and study groups. However, in logistic regression analysis, homozygous and heterozygous ADRA2A polymorphism, low socioeconomic status, comorbid diagnosis predicted a poorer response to treatment with methylphenidate. In conclusion, clinicians may plan drug free treatments for patients who have low socioeconomic status and comorbid diagnosis. On the other hand, it seems early for the use of our data about ADRA2A polymorphism in either treatment plans or phenotypic grouping. Further studies in different ethnic groups are needed to draw absolute conclusions for this polymorphism.