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

Abstract

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.

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

“…To be noted that this is the first time, for CpG methylation data, that a matrix of pairwise correlations is investigated in a control group (composed of healthy volunteers). So far, the same innovative approach was only applied to clinical groups, composed of either ADHD or Parkinsonian patients and in Internet Addiction (Lambacher et al, 2020;Tafani et al, 2020;De Nardi et al, 2020). As far as the DAT1 5'-UTR is concerned, these clinicallyrecruited patients were characterized by an overall hypomethylated versus hyper-methylated vs. unchanged condition, respectively.…”

“…Within each matrix, pairwise correlations were run between pairs, defined as above. We limited our analysis to "most important" CpGs (Tonelli et al, 2020;De Nardi et al, 2020): with them, ten pairs can be formed. In these pairs, since each locus can enter as either methylated or de-methylated, we can have a total of 4 situations x 10 pairs = 40 permutations.…”

“…Methylation is also studied to understand the development of externalizing and internalizing phenotypes in the general population. Methylation of dopamine transporter (DAT1) gene plays a key role for the risk of ADHD (Adriani et al 2018;, addictive diseases (Hillemacher et al, 2009;Reyes et al, 2010;De Nardi et al, 2020) neurodegenerative disorders (Rubino et al, 2020;). DAT1 function is essential for normal dopaminergic neurotransmission since it terminates the actions of dopamine by rapidly removing it from the synapse.…”

Interaction Effects of DRD2 Genetic Polymorphism and Interpersonal Stress on Problematic Gaming in College Students

“…First, although the candidate genes of this study were included based on previous studies [ 15 , 16 , 17 ], other candidate genes related to dopamine functions may interplay with DRD2 genotypes in affecting problematic gaming. For example, the dopamine D4 receptor gene (DRD4) 48bp variable number of tandem repetition (VNTR) [ 16 , 75 ] and the dopamine transporter gene (DAT1) 40bp VNTR [ 76 ] have been associated with internet addiction. Therefore, because the effect of a single genetic variant on complex behavior such as problematic gaming is most likely minimal, examining the cumulative genetic effect of multiple dopamine-related genetic variants would identify a more comprehensive genetic profile.…”

Rich Get Richer: Extraversion Statistically Predicts Reduced Internet Addiction through Less Online Anonymity Preference and Extraversion Compensation

“…Like other addictions, internet addiction has a complex etiology with multiple contributing factors implicated. According to a biopsychosocial model of addiction [ 8 ], the development of internet addiction may involve contributions from neurobiological (e.g., genetics and neurotransmitters) [ 9 , 10 ], more stable psychological (e.g., personality features, impulsivity, inhibitory-control tendencies) [ 11 , 12 , 13 ], or more state-related psychological (e.g., stress, loneliness) factors [ 14 , 15 ], as well as factors related to social environment (e.g., social norms, family, school) [ 16 , 17 ]. Of these, personality tendencies have received considerable attention, in that they may influence risk for internet addiction [ 18 , 19 ].…”