Effects of agmatine, glutamate, arginine, and nitric oxide on executive functions in children with attention deficit hyp

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PSYCHIATRY AND PRECLINICAL PSYCHIATRIC STUDIES - ORIGINAL ARTICLE

Effects of agmatine, glutamate, arginine, and nitric oxide on executive functions in children with attention deficit hyperactivity disorder Seda Aybuke Sari1   · Dilara Ulger2 · Serpil Ersan3 · Deniz Bakir2 · Ayla Uzun Cicek1 · Firat Ismailoglu4 Received: 14 July 2020 / Accepted: 28 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020

Abstract In this study, we aimed to investigate the effects of agmatine, nitric oxide (NO), arginine, and glutamate, which are the metabolites in the polyamine pathway,  on the performance of executive functions (EF) in attention deficit hyperactivity disorder (ADHD). The ADHD group included 35 treatment-naive children (6–14 years old) who were ewly diagnosed with ADHD. The control group consisted of 35 healthy children with the same age and sex, having no previous psychiatric disorders. In the study groups, Stroop test (ST) and trail making test (TMT) were used to monitor EF, and blood samples were collected to measure agmatine with ultra-high-performance liquid chromatography and NO, glutamate, and arginine with enzyme-linked immunosorbent assay (ELISA). The EFs were significantly impaired in the ADHD group. The agmatine and arginine levels of the ADHD group were significantly higher than their peers. The NO and glutamate levels were also higher in the ADHD group compared to the control group, but these differences did not reach statistical significance. Children with ADHD had more difficulties during EF tasks compared to healthy children. The elevated NO and glutamate levels may be related with the impairment during EF tasks. Therefore, agmatine and arginine may increase to improve EF tasks through its inhibitory effect on the synthesis of NO and glutamate. Further studies are needed about polyamine pathway molecules to shed light on the pathophysiology of ADHD. Keywords  Attention deficit hyperactivity disorder · Executive functions · Agmatine · Nitric oxide · Glutamate · Polyamine pathway

Introduction Polyamines are aliphatic molecules that have an essential role in many functions, including cell proliferation, posttranscriptional regulation, modulation of synaptic activity, This study was presented at the 29th National Child and Adolescent Mental Health Congress as an oral presentation with the number S-037. * Seda Aybuke Sari [email protected] 1



Department of Child and Adolescent Psychiatry, Faculty of Medicine, Sivas Cumhuriyet University, Imaret Village, 58140 Sivas, Turkey

2



Department of Biochemistry, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey

3

Department of Biochemistry, Faculty of Medicine, Nigde Omer Halis University, Nigde, Turkey

4

Department of Computer Engineering, Faculty of Engineering, Sivas Cumhuriyet University, Sivas, Turkey



and modulation of ion channels (Celik et al. 2017). To date, the relationship of polyamines with psychiatric disorders such as schizophrenia, mood disorders, anxiety, and suicidal behavior has been investi