Serum neuregulin-1, neuregulin-2, neuregulin-3 levels in children with attention deficit and hyperactivity disorder

Objective: Attention Deficit Hyperactivity Disorder (ADHD), which is the most common neurodevelopmental disorder of childhood, is associated with various factors including genetic and environmental factors, but its etiology has not been clearly clarified yet. Growth factors are considered to be regulators of neurogenesis, gliogenesis, cellular migration, cell differentiation, synapse formation and, accordingly, neural development. There are many studies in the literature examining the relationship between ADHD and various growth factors. In this study, the comparison of serum levels of neuregulin-1 (NRG-1), neuregulin-2 (NRG-2) and neuregulin-3 (NRG-3), which are members of the neuregulin family, which is a growth factor, in children and adolescents with ADHD and healthy controls, and ADHD symptomatology. It was aimed to evaluate the relationship between the biochemical variables related to the severity of the disease. Method: The study patient group included 101 participants aged 8-18 years, who admitted to NEU Meram Medical Faculty Child and Adolescent Psychiatry Department, and were diagnosed with ADHD according to DSM-5 criteria. Sociodemographic data form, Hollingshead-Redich Scale, Schedule for Affective Disorders and Schizophrenia for School Aged Children, Present and Lifetime Version (K-SADS-PL) were applied by the clinician during the examinations of the children. Parents completed the DSM-IV-Based Screening and Evaluation Scale for Conduct Disorders in Children and Adolescents (Atilla Turgay). Children and adolescents participating in the study completed The Revised Child Anxiety and Depression Scale (RCADS). The control group included 51 participants, aged 8-18 years, without any psychopathology, without chronic, physical, metabolic, active infective diseases, who applied to Necmettin Erbakan University Meram Medical Faculty Pediatrics Department. Sociodemographic data form, Hollingshead-Redich Scale was completed by the clinician. Parents completed the Turgay DSM-IV-Based Child and Adolescent Behavioral Disorders Screening and Rating Scale (T-DSM-IV-S). Children and adolescents participating in the study completed The Revised Child Anxiety and Depression Scale (RCADS). Serum neuregulin-1, neuregulin-2 and 5 ml venous blood samples were obtained from all participants in the patient and control groups and centrifuged. The levels of biochemical variables in serum samples were determined by Enzyme Linked Immuno Sorbent Assay (ELISA) method. Results: In our study, serum NRG-1 and NRG-3 levels were found to be statistically significantly higher in the ADHD group compared to the control group. There was no significant difference between the groups in terms of serum NRG-2 levels. A positive and significant correlation was found between NRG-1 serum level and T-DSM-IV-O parent form hyperactivity/impulsivity subscale scores. No correlation was found between serum NRG-2 and serum NRG-3 levels and T-DSM-IV-O parent form subscales. Conclusion: Although we cannot clearly predict whether the high serum NRG-1 and NRG-3 levels we detected reflect their expression in the brain, it may be a marker of disruptions in the NRG-ErbB signaling pathway that organizes brain development, neurotransmission modulation, prefrontal cortex plasticity and various cognitive processes in ADHD. Further studies are needed to elucidate the relationship between the NRG family and ADHD. Keywords: ADHD, neuregulin-1, neuregulin-2, neuregulin-3