Epigenetic regulation of DAT gene promoter modulates the risk of externalizing and internalizing behaviors on a normative population: An explorative study

Carpentieri, Valentina; Cerniglia, Luca; Cimino, Silvia; Pucci, Mariangela; Pascale, Esterina; D’Addario, Claudio; Adriani, Walter

doi:10.1016/j.bbr.2021.113246

Cited by 8 publications

(13 citation statements)

References 29 publications

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“…The new approach based on cross-correlation of CpG loci, which was already studied on ADHD [21] and Parkinson's disease [22], was applied in this research focused on vulnerability to Internet addiction disorder. Some of these results found confirmation from other previous research, for example, the positive correlation between CpG2 and CpG3 which was also found in studies by Carpentieri et al [36] and by Tafani et al [22]. For the first time, an association was noted between the 3'-UTR genotype and a 5'-UTR intra-motif link (from the CpG5-CpG6 comparison).…”

Section: Discussionsupporting

confidence: 87%

“…The aspects of Internet addiction that lead to aggressive behaviors are externalizing phenotypes included in Achenbach's definition [38]. Therefore, we can hypothesize that the same positive relationship between CpG3 and CpG5 can be found in both the externalizing subgroup of the previous work [36] and in the high IAT subgroup of the current work. From scatterplot graphics, methylation levels in positions 3 and 5 seem to follow an ascendent line in the high IAT group and are negatively matched in control groups, particularly in genotype 10/10.…”

Section: Discussionsupporting

confidence: 50%

“…(submitted [36]), where CpGs1, 2, and 3 assumed the opposite tendency of CpG6, with the first motif opposite to the second one. Parkinsonian subjects developed anomalous links, e.g., CpG2 with 6 and CpG3 with 5 [22].…”

Section: Discussionmentioning

confidence: 99%

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Involvement of DAT1 Gene on Internet Addiction: Cross-Correlations of Methylation Levels in 5′-UTR and 3’-UTR Genotypes, Interact with Impulsivity and Attachment-Driven Quality of Relationships

Nardi

Carpentieri

Pascale

et al. 2020

IJERPH

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Internet influences our communication, social and work interactions, entertainment, and many other aspects of life. Even if the original purpose was to simplify our lives, an excessive and/or maladaptive use of it may have negative consequences. The dopamine transporter (DAT1) gene was studied in relation to addictions, including excessive use of the Internet. The crucial role of DAT1 was previously underlined in modulating emotional aspects, such as affiliative behaviors. The present research follows a new approach based on cross-correlation between (de)methylation levels in couples of CpG loci, as previously shown. We investigated the possible relationships between Internet addiction, impulsivity, quality of attachment, DAT1 genotypes (from the 3′-untranslated region (UTR) variable number of tandem repeats (VNTR) poly-morphism), and the dynamics of methylation within the 5’-UTR of the DAT1 gene. From a normative sample of 79 youths, we extrapolated three subgroups a posteriori, i.e., one “vulnerable” with high Internet Addiction Test (IAT) scores (and high Barrat Impulsivity Scale (BIS) scores; n = 9) and two “controls’’ with low BIS scores and 10/10 vs. 9/x genotype (n = 12 each). Controls also had a “secure” attachment pattern, while genotypes and attachment styles were undistinguished in the vulnerable subgroup (none showed overt Internet addiction). We found a strongly positive correlation in all groups between CpG2 and CpG3. An unsuspected relationship between the 3’-UTR genotype and a 5’-UTR intra-motif link was revealed by CpG5–CpG6 comparison. The negative correlation between the CpG3–CpG5 positions was quite significant in the control groups (both with genotype 10/10 and with genotype 9/x), whereas a tendency toward positive correlation emerged within the high IAT group. In conclusion, future attention shall be focused on the intra- and inter-motif interactions of methylation on the CpG island at the 5′-UTR of DAT1.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 50%

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Involvement of DAT1 Gene on Internet Addiction: Cross-Correlations of Methylation Levels in 5′-UTR and 3’-UTR Genotypes, Interact with Impulsivity and Attachment-Driven Quality of Relationships

Nardi

Carpentieri

Pascale

et al. 2020

IJERPH

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“…Adolescents who reported more externalizing problems from age 13 to 17 years tended to show a larger epigenetic age than chronological age (higher EA) at age 17 years. Previous studies have found links between externalizing symptoms and DNAm Carpentieri et al, 2021;Cicchetti & Handley, 2017) However, the only study we located that examined the links between externalizing symptoms and EA found a positive link with inflammation-related methylation profiles, but not with epigenetic age . Thus, to the best of our knowledge, this is the first study showing the potential effects of preceding externalizing problems on EA.…”

Section: Discussioncontrasting

confidence: 55%

Negative Parenting, Epigenetic Age, and Psychological Problems: Prospective Associations from Adolescence to Young Adulthood

Mastrotheodoros¹,

Boks²,

Rousseau³

et al. 2022

Preprint

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Background: Epigenetic clocks are based on DNA methylation levels of several genomic loci and have been developed as indices of biological ageing. Studies examining the effects of stressful environmental exposures have shown that stress is associated with differences between epigenetic age and chronological age (i.e., Epigenetic Age acceleration, EA). In this pre-registered longitudinal study, we examined the long-term effects of negative parenting and psychological adjustment throughout adolescence (ages 13 to 17 years) on EA in late adolescence (age 17 years) and EA changes from late adolescence to young adulthood (age 25 years). Further, we examined how (change in) EA is related to change in psychological adjustment from adolescence to young adulthood. Methods: We used data from a sample of 434 participants followed from age 13 to age 25, with saliva collected at ages 17 and 25, and we estimated EA using four commonly used epigenetic clocks. We analyzed the data in a Structural Equation Modeling framework. Results: While negative parenting was not related to EA nor change in EA, (change in) EA was related to developmental indices such as externalizing problems and self-concept clarity. Conclusions: Declining psychological well-being during young adulthood was preceded by EA.

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“…Our own studies on ADHD take into consideration the methylation pattern in the 5′-UTR of the DAT1 gene [ 10 ]. The correlation between methylation patterns in the 5′-UTR of the DAT1 gene and psychopathological condition or addiction has been widely used in previous studies [ 11 , 12 , 13 ]. In our last papers [ 14 , 15 ], we investigated whether the methylation pattern in the DAT1 gene (including the opposed DNA strand) can be influenced by the allelic genotype at 3′-UTR.…”

Section: Introductionmentioning

confidence: 99%

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

Carpentieri

Lambacher

Troianiello³

et al. 2023

Children

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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.

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Epigenetic regulation of DAT gene promoter modulates the risk of externalizing and internalizing behaviors on a normative population: An explorative study

Cited by 8 publications

References 29 publications

Involvement of DAT1 Gene on Internet Addiction: Cross-Correlations of Methylation Levels in 5′-UTR and 3’-UTR Genotypes, Interact with Impulsivity and Attachment-Driven Quality of Relationships

Involvement of DAT1 Gene on Internet Addiction: Cross-Correlations of Methylation Levels in 5′-UTR and 3’-UTR Genotypes, Interact with Impulsivity and Attachment-Driven Quality of Relationships

Negative Parenting, Epigenetic Age, and Psychological Problems: Prospective Associations from Adolescence to Young Adulthood

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

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