Epigenetic Regulation of the Promotor Region of Vascular Endothelial Growth Factor-A and Nerve Growth Factor in Opioid-Maintained Patients.

AIMS: The nerve growth factor (NGF) and the vascular endothelial growth factor-A (VEGF-A) may be of importance for psychiatric diseases including substance use disorders. The aim of the study was to identify differences in the regulation of both neuropeptides via the DNA-methylation status of the promotor regions of NGF and VEGF-A in different forms of maintenance therapy for opioid dependence and the related stress regulation via the hypothalamic-pituitary-adrenal axis. METHODS: We compared methylation levels of opioid-dependent patients receiving treatment with diamorphine (n = 28) or levomethadone (n = 54) and similar levels in a healthy control group (n = 72). RESULTS: There was a significantly higher methylation of VEGF-A in opioid-maintained patients with levomethadone compared to that in the control group (estimated marginal means [EMM] [SE]): 0.036 [0.003] vs. 0.020 [0.003]; p < 0.001). We performed a cluster analysis for NGF, splitting up the results in 4 clusters. We found significant changes in methylation rates of the opioid-maintained patients compared to the controls in cluster I ([EMM] [SE]: 0.064 [0.005] vs. 0.084 [0.006]; p = 0.03), cluster II ([EMM] [SE]: 0.133 [0.013] vs. 0.187 [0.014]; p < 0.001) and cluster III ([EMM] [SE]: 0.190 [0.014] vs. 0.128 [0.016]; p < 0.001). CONCLUSIONS: The results are of importance, as they indicate that long-term changes in stress regulation regulated by neurotrophines are a crucial part of the symptomatology of opioid dependence, thus influencing drug consumption and the different forms of opioid-maintenance therapies.

Task-Irrelevant Novel Sounds Improve Attentional Performance in Children With and Without ADHD.

Task-irrelevant salient stimuli involuntarily capture attention and can lead to distraction from an ongoing task, especially in children with ADHD. However, there has been tentative evidence that the presentation of novel sounds can have beneficial effects on cognitive performance. In the present study, we aimed to investigate the influence of novel sounds compared to no sound and a repeatedly presented standard sound on attentional performance in children and adolescents with and without ADHD. We therefore had 32 patients with ADHD and 32 typically developing children and adolescents (8 to 13 years) execute a flanker task in which each trial was preceded either by a repeatedly presented standard sound (33%), an unrepeated novel sound (33%) or no auditory stimulation (33%). Task-irrelevant novel sounds facilitated attentional performance similarly in children with and without ADHD, as indicated by reduced omission error rates, reaction times, and reaction time variability without compromising performance accuracy. By contrast, standard sounds, while also reducing omission error rates and reaction times, led to increased commission error rates. Therefore, the beneficial effect of novel sounds exceeds cueing of the target display by potentially increased alerting and/or enhanced behavioral control.