In view of the need for easily accessible biomarkers, we evaluated in ADHD children the epigenetic status of the 5′-untranslated region (UTR) in the SLC6A3 gene, coding for human dopamine transporter (DAT). We analysed buccal swabs and sera from 30 children who met DSM-IV-TR criteria for ADHD, assigned to treatment according to severity. Methylation levels at six-selected CpG sites (among which, a CGGCGGCGG and a CGCG motif), alone or in combination with serum titers in auto-antibodies against dopamine transporter (DAT aAbs), were analysed for correlation with CGAS scores (by clinicians) and Conners’ scales (by parents), collected at recruitment and after 6 weeks. In addition, we characterized the DAT genotype, i.e., the variable number tandem repeat (VNTR) polymorphisms at the 3′-UTR of the gene. DAT methylation levels were greatly reduced in ADHD patients compared to control, healthy children. Within patients carrying at least one DAT 9 allele (DAT 9/x), methylation at positions CpG2 and/or CpG6 correlated with recovery, as evident from delta-CGAS scores as well as delta Conners’ scales (‘inattentive’ and ‘hyperactive’ subscales). Moreover, hypermethylation at CpG1 position denoted severity, specifically for those patients carrying a DAT 10/10 genotype. Intriguingly, high serum DAT-aAbs titers appeared to corroborate indications from high CpG1 versus high CpG2/CpG6 levels, likewise denoting severity versus recovery in DAT 10/10 versus 9/x patients, respectively. These profiles suggest that DAT 5′UTR epigenetics plus serum aAbs can serve as suitable biomarkers, to confirm ADHD diagnosis and/or to predict the efficacy of treatment.

Potential for diagnosis versus therapy monitoring of attention deficit hyperactivity disorder: a new epigenetic biomarker interacting with both genotype and auto-immunity / Adriani, Walter; Romano, Emilia; Pucci, Mariangela; PASCALE, ESTERINA; CERNIGLIA, LUCA; CIMINO, SILVIA; TAMBELLI, Renata; CURATOLO, Paolo; Granstrem, Oleg; Maccarrone, Mauro; Laviola, Giovanni; D’Addario, Claudio. - In: EUROPEAN CHILD & ADOLESCENT PSYCHIATRY. - ISSN 1018-8827. - STAMPA. - 27:2(2018), pp. 241-252. [10.1007/s00787-017-1040-9]

Potential for diagnosis versus therapy monitoring of attention deficit hyperactivity disorder: a new epigenetic biomarker interacting with both genotype and auto-immunity

PASCALE, ESTERINA;CERNIGLIA, LUCA;CIMINO, SILVIA;TAMBELLI, Renata;CURATOLO, Paolo;
2018

Abstract

In view of the need for easily accessible biomarkers, we evaluated in ADHD children the epigenetic status of the 5′-untranslated region (UTR) in the SLC6A3 gene, coding for human dopamine transporter (DAT). We analysed buccal swabs and sera from 30 children who met DSM-IV-TR criteria for ADHD, assigned to treatment according to severity. Methylation levels at six-selected CpG sites (among which, a CGGCGGCGG and a CGCG motif), alone or in combination with serum titers in auto-antibodies against dopamine transporter (DAT aAbs), were analysed for correlation with CGAS scores (by clinicians) and Conners’ scales (by parents), collected at recruitment and after 6 weeks. In addition, we characterized the DAT genotype, i.e., the variable number tandem repeat (VNTR) polymorphisms at the 3′-UTR of the gene. DAT methylation levels were greatly reduced in ADHD patients compared to control, healthy children. Within patients carrying at least one DAT 9 allele (DAT 9/x), methylation at positions CpG2 and/or CpG6 correlated with recovery, as evident from delta-CGAS scores as well as delta Conners’ scales (‘inattentive’ and ‘hyperactive’ subscales). Moreover, hypermethylation at CpG1 position denoted severity, specifically for those patients carrying a DAT 10/10 genotype. Intriguingly, high serum DAT-aAbs titers appeared to corroborate indications from high CpG1 versus high CpG2/CpG6 levels, likewise denoting severity versus recovery in DAT 10/10 versus 9/x patients, respectively. These profiles suggest that DAT 5′UTR epigenetics plus serum aAbs can serve as suitable biomarkers, to confirm ADHD diagnosis and/or to predict the efficacy of treatment.
2018
attention deficit disorder with hyperactivity; genes; transporter gene
01 Pubblicazione su rivista::01a Articolo in rivista
Potential for diagnosis versus therapy monitoring of attention deficit hyperactivity disorder: a new epigenetic biomarker interacting with both genotype and auto-immunity / Adriani, Walter; Romano, Emilia; Pucci, Mariangela; PASCALE, ESTERINA; CERNIGLIA, LUCA; CIMINO, SILVIA; TAMBELLI, Renata; CURATOLO, Paolo; Granstrem, Oleg; Maccarrone, Mauro; Laviola, Giovanni; D’Addario, Claudio. - In: EUROPEAN CHILD & ADOLESCENT PSYCHIATRY. - ISSN 1018-8827. - STAMPA. - 27:2(2018), pp. 241-252. [10.1007/s00787-017-1040-9]
File allegati a questo prodotto
File Dimensione Formato  
Adriani_Diagnosis-ADHD_2018.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 2.49 MB
Formato Adobe PDF
2.49 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/999634
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 45
  • ???jsp.display-item.citation.isi??? 40
social impact