Effect of NR3C1 and COMT genes in attention deficit hyperactivity disorder and comorbid aggression

Objective: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in childhood, and the accompanying aggression results in a substantial number of visits to child and adolescent psychiatry clinics. To date, the etiological differences that contribute to aggression in patients diagnosed with ADHD remain unclear. This study aims to investigate the relationship between the NR3C1 and COMT genes in children with ADHD and accompanying aggression. Should a significant difference be identified among the parameters examined in our study, it would be advantageous in clinical practice to implement complementary interventions when formulating treatment plans for patients diagnosed with ADHD who exhibit aggression. Method: The research was conducted between May 2023 and May 2024 at the Department of Child and Adolescent Mental Health and Diseases Clinic, Manisa Celal Bayar University Faculty of Medicine. The study sample comprised 180 patients aged 6-18 years who were admitted to the Manisa Celal Bayar University Child and Adolescent Mental Health and Diseases Clinic, diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) through clinical psychiatric interviews using the "Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL)," and who met the inclusion criteria for the study. Subsequently, the families of the patient group were provided with the "sociodemographic data form," "LEVEL 2 – Irritability – Parent/Guardian of Child Age 6- 17" and the children or adolescents included in the study were administered the "CRIES-13 Scale" and the "Difficulties in Emotion Regulation Scale." The group diagnosed with both aggression and ADHD was designated as the case group, while children and adolescents diagnosed with only ADHD constituted the control group. The case group with ADHD and accompanying aggression consisted of 69 individuals, while the group diagnosed with only ADHD consisted of 111 individuals. On the day of psychometric assessment, approximately 2 mL of peripheral venous blood was drawn from the cases forming the ADHD and control groups, followed by DNA isolation. Subsequently, primers for the amplification of the COMT rs4690 and NR3C1 rs10052957 gene regions via Polymerase Chain Reaction (PCR) were designed. These gene regions were then amplified via PCR, the amplification products were analyzed by Sanger sequencing, and the nucleotide sequences of the target gene regions were analyzed. Results: Our study found statistically significant correlations between physical aggression and parental marital status, the type of complications experienced during birth, and the goal-directed behavior subscale of the Difficulties in Emotion Regulation Scale; between verbal aggression and parental marital status, parental education level, regular medication use by parents, and previous psychiatric treatment of the parent or child; and between previous psychiatric treatment of the child. Additionally, statistically significant correlations were identified between holding grudges and hostility and regular medication use by parents, previous psychiatric treatment of the child, the COMT gene, the number of cytosine (C) alleles in the NR3C1 gene, and the number of adenine (A) and guanine (G) alleles in the COMT gene. Keywords: ADHD, aggression, NR3C1, COMT