Evaluation of the regulatory role of circadian rhythm related long non-coding RNAS in attention deficit hyperactivity disorder etiogenesis

ADHD is a lifelong neurodevelopmental disorder that is common in children and adolescents. Studies have found that sleep problems are common in children with ADHD, and the chronotypic features of these children differ from healthy controls. Therefore, it is thought that the circadian rhythm may have an important place in the etiogenesis of ADHD, but the processes that regulate the circadian rhythm in ADHD have not been fully elucidated yet. In this study, it was aimed to compare children with ADHD and healthy controls in terms of chronotypic features and expression levels of CLOCK, PER1 genes, which are the main circadian clock genes, and lncRNA HULC, lncRNA UCA1 genes, which were previously shown to be associated with circadian rhythm. 43 children with ADHD combined type and 40 healthy controls were included in the study. After the semi-structured interview with the participants, the Emotional Reactivity Scale, Conner's Parent Rating Scale-Revised Short Form, Childhood Chronotype Questionnaire, and Children's Sleep Disorders Scale were administered. In order to determine gene expression levels, peripheral blood samples were taken from the participants at 09:00 in the morning. As a result of our study, it was determined that evening chronotype was seen at higher rates, sleep initiation and maintenance disorder, sleep-wake transition disorder and excessive sleepiness disorder were more common and the level of irritability was higher in ADHD patients compared to controls. CLOCK, PER1, lncRNA HULC, lncRNA UCA1 gene expression levels were statistically significantly higher in the ADHD group than in the control group (p<0.05). While there was no relationship between the expression levels of CLOCK, PER1, lncRNA HULC and lncRNA UCA1 genes in the ADHD group and chronotypic features, average sleep duration, social jetlag, SJLsc and sleep debt; A weak positive correlation was found between CLOCK expression level and severity of hyperactivity (r=0.314; p=0.041), and between HULC expression level and severity of opposition (r=0.315; p=0.040). It was determined that sleep disorder increased the presence of ADHD 5.01 times (p=0.002), increasing age decreased the presence of ADHD by 1.4 times (p=0.020), and gender was not a risk factor for the presence of ADHD (p=0.307). Our study is the first to show the relationship between ADHD and lncRNA HULC and lncRNA UCA1, and our results show that both lncRNAs may have a role in the etiology of ADHD. In addition, circadian rhythm and sleep problems are also important in the etiology of ADHD. Considering that lncRNAs play a regulatory role in many cellular processes, more research is needed to elucidate their role in ADHD etiogenesis.