The Association Between DNA Methylation and Loneliness in Early Adolescence: Hypervigilance to Social Threat as an Intermediary Mechanism

A hypervigilance toward social threats, defined as a heightened sensitivity to socially threatening stimuli, is considered a key risk factor for loneliness (Cacioppo & Hawkley, 2009). During the early stages of social information processing, such hypervigilance to social threats may manifest as attentional biases that influence how individuals allocate their attentional resources when exposed to socially threatening information (Spithoven et al., 2017). Previous research suggests a positive association between facilitated attention to social threats, which is defined as a faster orientation toward socially threatening stimuli, and loneliness (Bangee et al., 2014; Qualter et al., 2013). However, hypervigilance to social threat may also influence other components of attentional bias, such as difficulties disengaging one’s attention away from socially threatening stimuli, whose role in the development of loneliness remains unclear. Therefore, the first objective of this study is to examine whether attentional disengagement difficulties are a risk factor for loneliness in early adolescence. Furthermore, little is known about the biological processes that may underlie hypervigilance to social threats and its associated attentional disengagement difficulties. A possible biological process that may contribute to these difficulties is DNA methylation, an epigenetic process that affects gene expression (Lester et al., 2016). Therefore, the second objective of this study is to examine whether DNA methylation in stress-related genes predicts these attentional disengagement difficulties associated with hypervigilance to social threat. Additionally, because there is initial evidence for an association between DNA methylation in stress-related genes and loneliness (Koopmans et al., 2023), the third objective of the current study is to examine whether attentional disengagement difficulties may mediate the association between DNA methylation and loneliness in early adolescence. To investigate these objectives, we developed a novel attentional disengagement task that builds on traditional evaluative priming paradigms (Fazio et al., 1986). In this task, adolescents were presented with prime-target word pairs, where the primes were either neutral or emotionally valanced (socially or emotionally negative). After each prime a target word appeared and adolescents were asked to quickly determine whether the target word was positive or negative. In this task, we would expect that difficulties in disengaging attention from negative primes would be reflected by longer reaction times (RTs) on trials with negative primes compared to trials with neutral primes, regardless of the valence of the target. Although the task was adapted specifically to assess attentional disengagement, it retained many similarities to the original evaluative priming task. Therefore, we will also examine possible congruency effects (i.e., shorter RTs for congruent prime-target pairs, such as negative primes followed by negative targets) and incongruency effects (i.e., longer RTs for incongruent prime-target pairs, such as negative primes followed by positive targets) and how these effects are associated with DNA methylation and loneliness as part of alternative hypotheses.