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.

Loneliness is a prevalent condition with adverse effects on physical and mental health. Evolutionary theories suggest it evolved to drive people to reconnect. However, chronic loneliness may result in a negative social bias and self-preservation behaviors, paradoxically driving individuals away from social interactions. Lonely people often feel they are not close to anyone; however, little is known about their interpersonal distance preferences. During COVID-19, many experienced situational loneliness related to actual social isolation. Therefore, there was a unique opportunity to examine both chronic and situational (COVID-19-related) loneliness. In the present study, 479 participants completed an online task that experimentally assessed interpersonal distance preferences in four conditions—passively being approached by a friend or a stranger, and actively approaching a friend or a stranger. Results show that high chronic loneliness was related to a greater preferred distance across conditions. Intriguingly, by contrast, high COVID-19-related loneliness was related to a smaller preferred distance across conditions. These findings provide further support for the evolutionary theory of loneliness: situational loneliness indeed seems to drive people towards reconnection, while chronic loneliness seems to drive people away from it. Implications for the amelioration of chronic loneliness are discussed based on these findings.

Loneliness is a public health concern with detrimental effects on physical and mental well-being. Given phenotypical overlaps between loneliness and social anxiety (SA), cognitive-behavioral interventions targeting SA might be adopted to reduce loneliness. However, whether SA and loneliness share the same underlying neurocognitive mechanisms is still an elusive question. The current study aimed at investigating to what extent known behavioral and neural correlates of social avoidance in SA are evident in loneliness. We used a prestratified approach involving 42 (21 females) participants with high loneliness (HL) and 40 (20 females) participants with low loneliness (LL) scores. During fMRI, participants completed a social gambling task to measure the subjective value of engaging in social situations and responses to social feedback. Univariate and multivariate analyses of behavioral and neural data replicated known task effects. However, although HL participants showed increased SA, loneliness was associated with a response pattern clearly distinct from SA. Specifically, contrary to expectations based on SA differences, Bayesian analyses revealed moderate evidence for equal subjective values of engaging in social situations and comparable amygdala responses to social decision-making and striatal responses to positive social feedback in both groups. Moreover, while explorative analyses revealed reduced pleasantness ratings, increased striatal activity, and decreased striatal-hippocampal connectivity in response to negative computer feedback in HL participants, these effects were diminished for negative social feedback. Our findings suggest that, unlike SA, loneliness is not associated with withdrawal from social interactions. Thus, established interventions for SA should be adjusted when targeting loneliness.SIGNIFICANCE STATEMENTLoneliness can cause serious health problems. Adapting well-established cognitive-behavioral therapies targeting social anxiety might be promising to reduce chronic loneliness given a close link between both constructs. However, a better understanding of behavioral and neurobiological factors associated with loneliness is needed to identify which specific mechanisms of social anxiety are shared by lonely individuals. We found that lonely individuals show a consistently distinct pattern of behavioral and neural responsiveness to social decision-making and social feedback compared with previous findings for social anxiety. Our results indicate that loneliness is associated with a biased emotional reactivity to negative events rather than social avoidance. Our findings thus emphasize the distinctiveness of loneliness from social anxiety and the need for adjusted psychotherapeutic protocols.

Lonely people tend to evaluate social exchanges negatively and to display difficulties in interactions. Interpersonal synchronization is crucial for achieving positive interactions, promoting affinity, closeness, and satisfaction. However, little is known about lonely individuals’ ability to synchronize and about their brain activity while synchronizing. Following the screening of 303 participants, we recruited 32 low and 32 high loneliness participants. They were scanned while engaged in movement synchronization, using a novel dyadic interaction paradigm. Results showed that high loneliness individuals exhibited a reduced ability to adapt their movement to their partner’s movement. Intriguingly, during movement adaptation periods, high loneliness individuals showed increased activation in the action observation (AO) system, specifically in the inferior frontal gyrus and the inferior parietal lobule. They did not show increased activation in the dorsomedial prefrontal cortex, which in the context of synchronization was suggested to be related to gap-monitoring. Based on these findings, we propose a model according to which lonely people may require stronger activation of their AO system for alignment, to compensate for some deficiency in their synchronization ability. Despite this hyperactivation, they still suffer from reduced synchronization capacity. Consequently, synchronization may be a relevant intervention area for the amelioration of loneliness.