Genetic analysis of sluggish cognitive tempo (SCT) symptoms with dopaminergic pathway in attention deficit hyperactivity disorder (ADHD)

Objective: Attention Deficit and Hyperactivity Disorder (ADHD) is a multifactorial and polygenic disease with high inheritance. Up to now, variants associated with the diagnosis of ADHD can explain a very small proportion of pathogenesis. The most important reason for this is the phenotypic heterogeneity in ADHD cases. Studies to reduce ADHD heterogeneity have increased interest in researching the concept of Sluggish Cognitive Tempo (SCT). The aim of this study was to decrease the clinical heterogeneity of ADHD and to investigate the relationship of these variants with the diagnosis of SCT in order to increase the representation of the genetic variants identified in ADHD patients as biomarkers. Materials and Methods: In our study, 26 cases with SCT, 69 cases with SCT-ADHD were compared with 147 cases with ADHD and 92 healthy controls. DAT1 (40 bp repeat region in the 3' UTR region) and DRD4 gene (48 bp repeat region in the exon 3) were examined in cases diagnosed with SCT or ADHD and healthy controls. In addition, BDNF (rs6265), SNAP-25 (rs3746544-rs1051312) and SYN3 (rs133945-rs133946) polymorphisms were evaluated by RFLP method. Results: There was a statistically significant difference between the groups in the DAT1, DRD4 and BDNF genes (p <0.05) and there was no significant difference in SNAP-25 and SYN3 genes (p> 0.05). The 10R / 10R genotype for the DAT1 gene, the 7R allele for the DRD4 gene and the A allele for the BDNF gene were found in the highest rate of SCT cases. Conclusion: It has been reported in previous studies that patients with symptoms of SCT are unresponsive to methylphenidate treatment that is main pharmacological treatment of ADHD. Genetic markers associated with decreased methylphenidate response in pharmacological studies associated with ADHD are the 10R / 10R genotype for the DAT1 gene, the 7R allele for the DRD4 gene, and the A allele for the BDNF gene. In our study, alleles associated with unresponsiveness to methylphenidate were found to be higher in SCT cases than in both healthy controls and ADHD cases. The results of our study indicate the necessity of investigating the symptoms of ADHD as well as the symptoms of SCT in ADHD candidate gene studies and pharmacogenetic studies. It is the first candidate gene study to be used for the diagnosis of SCT, and the findings need to be supported by pharmacogenetic studies.