Molecular genetics of neurotransmitters and neuropeptides involved in Internet use disorders including first insights on a potential role of hypothalamus' oxytocin hormone.

This chapter covers the phenomenon of Internet use disorders (IUDs) and putative associations with different neurotransmitter and neuropeptide systems. Genes coding for such messengers can be seen as an important starting point in the complicated quest to understand human behavior including new phenomena such as IUDs. Therefore, a special focus of this chapter will lie on individual differences in molecular genetic underpinnings of neurotransmitter and neuropeptide systems and their associations with individual differences in tendencies towards IUDs. By shedding light on these associations, putative predisposing molecular genetic factors for the emergence and maintenance of IUDs can be carved out. Therefore, first an introduction to IUDs and a model that can guide research on putative associations of IUDs with different specific neurotransmitters and neuropeptides will be presented. Subsequently, twin studies on the heritability of IUDs are reviewed. Finally, studies on differences in molecular genetic predispositions and their associations with differences in IUDs will be presented and discussed, including targets related to the dopaminergic and serotonergic system as well as the hypothalamic neuropeptide oxytocin. The chapter closes with a conclusion about what is already known and what needs to be investigated in future studies to gain further insights into putative associations between molecular genetic markers and IUDs.

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.

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.

Problematic internet use: an exploration of associations between cognition and COMT rs4818, rs4680 haplotypes.

OBJECTIVE: Problematic internet users suffer from impairment in a variety of cognitive domains. Research suggests that COMT haplotypes exert differential effects on cognition. We sought to investigate differences in the genetic profiles of problematic internet users and whether those could shed light on potential cognitive differences. METHODS: We recruited 206 non-treatment seeking participants with heightened impulsive traits and obtained cross-sectional demographic, clinical, and cognitive data as well as the genetic haplotypes of COMT rs4680 and rs4818. We identified 24 participants who presented with problematic internet use (PIU) and compared PIU and non-PIU participants using one-way analysis of variance (ANOVA) and chi square as appropriate. RESULTS: PIU was associated with worse performance on decision making, rapid visual processing, and spatial working memory tasks. Genetic variants were associated with altered cognitive performance, but rates of PIU did not statistically differ for particular haplotypes of COMT. CONCLUSION: This study indicates that PIU is characterized by deficits in decision making and working memory domains; it also provides evidence for elevated impulsive responses and impaired target detection on a sustained attention task, which is a novel area worth exploring further in future work. The effects observed in the genetic influences on cognition of PIU subjects imply that the genetic heritable components of PIU may not lie within the genetic loci influencing COMT function and cognitive performance; or that the genetic component in PIU involves many genetic polymorphisms each conferring only a small effect.