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Loneliness is a painful condition associated with increased risk for premature mortality. The formation of new, positive social relationships can alleviate feelings of loneliness, but requires rapid trustworthiness decisions during initial encounters and it is still unclear how loneliness hinders interpersonal trust. Here, a multimodal approach including behavioral, psychophysiological, hormonal, and neuroimaging measurements is used to probe a trust-based mechanism underlying impaired social interactions in loneliness. Pre-stratified healthy individuals with high loneliness scores (n = 42 out of a screened sample of 3678 adults) show reduced oxytocinergic and affective responsiveness to a positive conversation, report less interpersonal trust, and prefer larger social distances compared to controls (n = 40). Moreover, lonely individuals are rated as less trustworthy compared to controls and identified by the blinded confederate better than chance. During initial trust decisions, lonely individuals exhibit attenuated limbic and striatal activation and blunted functional connectivity between the anterior insula and occipitoparietal regions, which correlates with the diminished affective responsiveness to the positive social interaction. This neural response pattern is not mediated by loneliness-associated psychological symptoms. Thus, the results indicate compromised integration of trust-related information as a shared neurobiological component in loneliness, yielding a reciprocally reinforced trust bias in social dyads., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The risk for developing stress-related disorders is elevated in individuals with high alexithymia, a personality trait characterized by impaired emotional awareness and interpersonal relating. However, it is still unclear how alexithymia alters perceived psychosocial stress and which neurobiological substrates are mechanistically involved. To address this question, we examined freshmen during transition to university, given that this period entails psychosocial stress and frequently initiates psychopathology. Specifically, we used a functional magnetic resonance imaging emotional face matching task to probe emotional processing in 54 participants (39 women) at the beginning of the first year at university and 6 months later. Furthermore, we assessed alexithymia and monitored perceived psychosocial stress and loneliness via questionnaires for six consecutive months. Perceived psychosocial stress significantly increased over time and initial alexithymia predicted subjective stress experiences via enhanced loneliness. On the neural level, alexithymia was associated with lowered amygdala responses to emotional faces, while loneliness correlated with diminished reactivity in the anterior insular and anterior cingulate cortex. Furthermore, insula activity mediated the association between alexithymia and loneliness that predicted perceived psychosocial stress. Our findings are consistent with the notion that alexithymia exacerbates subjective stress via blunted insula reactivity and increased perception of social isolation., (© 2021. The Author(s).)