Methylation Dynamics on 5'-UTR of DAT1 Gene as a Bio-Marker to Recognize Therapy Success in ADHD Children.

Attention-deficit/hyperactivity disorder (ADHD), a neuropsychiatric condition characterized by inattention, hyperactivity, and impulsivity, afflicts 5% of children worldwide. Each ADHD patient presents with individual cognitive and motivational peculiarities. Furthermore, choice of appropriate therapy is still up to clinicians, who express somewhat qualitative advice on whether a child is being successfully cured or not: it would be more appropriate to use an objective biomarker to indicate whether a treatment led to benefits or not. The aim of our work is to search for such clinical biomarkers. We recruited 60 ADHD kids; psychopathological scales were administered at recruitment and after six weeks of therapy. Out of such a cohort of ADHD children, we rigorously extracted two specific subgroups; regardless of the initial severity of their disease, we compared those who obtained the largest improvement (ΔCGAS > 5) vs. those who were still characterized by a severe condition (CGAS < 40). After such a therapy, methylation levels of DNA extracted from buccal swabs were measured in the 5'-UTR of the DAT1 gene. CpGs 3 and 5 displayed, in relation to the other CpGs, a particular symmetrical pattern; for "improving" ADHD children, they were methylated together with CpG 2 and CpG 6; instead, for "severe" ADHD children, they accompanied a methylated CpG 1. These specific patterns of methylation could be used as objective molecular biomarkers of successful cures, establishing if a certain therapy is akin to a given patient (personalized medicine). Present data support the use of post-therapy molecular data obtained with non-invasive techniques.

Search for an epigenetic biomarker in ADHD diagnosis, based on the DAT1 gene 5'-UTR methylation: a new possible approach.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most common neuro-developmental alteration in childhood. To date, its diagnosis is exclusively clinical, however recent studies focused on searching for objective biomarkers. We recently reported a selective alteration of DNA methylation in the 5'-UTR of dopamine transporter (DAT1) gene, in a 1CGG2CGG3CGG and a 5CG6CG motif, for ADHD patients (compared to controls). Presently, we looked for DNA methylation of the corresponding CpG sites but complementary on the opposite strand ("COS"). Exploiting a novel cross-correlation approach, we found a core M5 - M5 COS and M2 - M2 COS relationship with relatively free M1 and M6 COS extremes. Our data might be relevant, to find a new biomarker to diagnose ADHD in affected subjects.