RESUMEN
Objective: The objective of this study was to compare quantitative electroencephalography (Q-EEG) characteristics of children with Attention-deficit/hyperactivity disorder (ADHD), taking into account the presence of a comorbidity for anxiety disorder. It also sought to investigate the impact of comorbid anxiety on the Q-EEG heterogeneity of children with ADHD. Method: A total of 141 children with ADHD but without comorbid anxiety (ADHD-Only), 25 children with a comorbidity for anxiety disorder (ADHD-ANX) and 43 children in the control group were assessed. To compare Q-EEG characteristics between groups, we performed ANCOVA (Analysis of Covariance) on relative power and theta/beta ratio (TBR) controlling for covariates such as age, sex, and FSIQ. Relative power values from 19 electrodes were averaged for three regions (frontal, central and posterior). Furthermore, cluster analysis (Ward's method) using the squared Euclidian distance was conducted on participants with ADHD to explore the impact of anxiety on the heterogeneity of Q-EEG characteristics in ADHD. Results: There were no significant group differences in cognitive and behavioral measures. However, significant differences between groups were observed in the theta values in the central region, and the beta values in the frontal, central and posterior regions. In post hoc analyses, It was found that the ADHD-ANX group has significantly higher beta power values than the ADHD-Only group in all regions. For the theta/beta ratio, the ADHD-Only group had significantly higher values than the ADHD-ANX group in frontal, central and posterior regions. However, the control group did not show significant differences compared to both the ADHD-Only and ADHD-ANX group. Through clustering analysis, the participants in the ADHD-Only and ADHD-ANX groups were classified into four clusters. The ratios of children with comorbidities for anxiety disorder within each cluster were significantly different (χ2 = 10.018, p = 0.019). Conclusion: Attention-deficit/hyperactivity disorder children with comorbid anxiety disorder showed lower theta power in the central region, higher beta power in all regions and lower TBR in all regions compared to those without comorbid anxiety disorder. The ratios of children with comorbidities for anxiety disorder within each cluster were significantly different.
RESUMEN
Inositol polyphosphates (IPs) are a group of inositol metabolites that act as secondary messengers for external signalling cues. They play various physiological roles such as insulin release, telomere length maintenance, cell metabolism, and aging. Inositol hexakisphosphate kinase 2 (IP6K2) is a key enzyme that produces 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-IP7), which influences the early stages of glucose-induced exocytosis. Therefore, regulation of IP6Ks may serve as a promising strategy for treating diseases such as diabetes and obesity. In this study, we designed, synthesised, and evaluated flavonoid-based compounds as new inhibitors of IP6K2. Structure-activity relationship studies identified compound 20s as the most potent IP6K2 inhibitor with an IC50 value of 0.55 µM, making it 5-fold more potent than quercetin, the reported flavonoid-based IP6K2 inhibitor. Compound 20s showed higher inhibitory potency against IP6K2 than IP6K1 and IP6K3. Compound 20s can be utilised as a hit compound for further structural modifications of IP6K2 inhibitors.
