Stable and dynamic neurobehavioral phenotypes of social isolation and loneliness in serious mental illness

总结 严重精神疾病（SMI）最令人衰弱和有害的方面是：1）社会孤立 (low社会联系的数量）和2）社会脱节（孤独）的主观体验， 经常伴随着这些症状。社会孤立和孤独极大地影响了日常运作， 与SMI患者心脏代谢健康状况差和早期死亡率相关，目前尚无可用的 治疗可以预防或逆转这些疾病的破坏性后果。这可能是 部分原因是SMI中社会孤立和孤独的神经和心理机制， 它们如何影响健康结果，人们知之甚少。然而，最近的研究表明， 先进的神经影像学和数字评估已经形成了一种新的研究方法的基础， 这些机制在本提案中得到了概述。先前的研究表明，客观的孤立和孤独是 相互关联，但也有些独立。最近的神经影像学研究结果支持这一模型，揭示了， 社交孤立和孤独都有共同的和不同的神经相关性。但是，同样清楚的是， 不是静态的现象;基于智能手机的评估揭示了社会的短暂，动态变化 孤独和寂寞。预期被拒绝的个体差异与短暂的 孤独的经历，更大的回避和随后的社会孤立的增加。因此，在目前 应用，我们建议全面衡量相对稳定的神经和行为预测因子 社会孤立和孤独，以及这些经历的每时每刻的变化，在60 SMI患者和60名对照受试者。在拟议项目的目标1中，我们将表明， SMI中的社会孤立和孤独与对社会刺激的共享和不同的神经反应有关， 与社会孤立有关的社会感知相关回路（内侧颞叶区域）的反应不足， 以及与孤独有关的奖赏相关回路（基底神经节区域）的反应不足。在目标2中，我们 使用纵向智能手机评估来测量社交孤立和孤独的瞬时变化， “突发”设计。最后，在目标3中，我们将确定社交孤立和孤独的量化指标 目标1和2中确定的预测心脏代谢健康指数，测量这些关联的稳定性 随着时间因此，在这个项目中，我们将展示基本的神经和行为过程驱动瞬时的 社会隔离和孤独的经验的变化，并直接影响心脏代谢健康的SMI。 在后续工作中，这些发现可以作为新干预措施研究的客观目标， 解决这些早期死亡的主要原因。

Summary Some of the most debilitating and harmful aspects of serious mental illnesses (SMI) are the 1) social isolation (low numbers of social contacts) and 2) the subjective experiences of social disconnection (loneliness) that frequently accompany these conditions. Social isolation and loneliness greatly impact day-to-day functioning and are associated with poor cardiometabolic health and early mortality in SMI, and currently there are no available treatments that can prevent or reverse these devastating consequences of having these illnesses. This may be in part because the neural and psychological mechanisms underlying social isolation and loneliness in SMI, and how they impact health outcomes, are poorly understood. However, recent clues from studies employing advanced neuroimaging and digital assessments have formed the basis of a novel approach to investigating such mechanisms, outlined in this proposal. Prior work has indicated that objective isolation and loneliness are correlated but also somewhat independent. Recent neuroimaging findings support this model, revealing that social isolation and loneliness have both shared and distinct neural correlates. However, it is also clear that these are not static phenomena; smartphone-based assessments have revealed transient, dynamic changes in social isolation and loneliness. Individual differences in the anticipation of rejection are associated with momentary experiences of loneliness, greater avoidance and subsequent increases in social isolation. Thus, in the current application, we propose to comprehensively measure both the relatively stable neural and behavioral predictors of social isolation and loneliness, as well as the moment-to-moment changes in these experiences, in 60 individuals with SMI and 60 control subjects. In Aim 1 of the proposed project, we will show that the higher levels of social isolation and loneliness in SMI are linked to shared and distinct neural responses to social stimuli, with deficient responses of social perception-related circuitry (medial temporal lobe regions) linked to social isolation, and deficient responses of reward-related circuitry (basal ganglia regions) linked to loneliness. In Aim 2, we will measure transient changes in social isolation and loneliness with smartphone assessments using a longitudinal “burst” design. Lastly, in Aim 3, we will determine how the quantitative markers of social isolation and loneliness identified in Aims 1 and 2 predict indices of cardiometabolic health, measuring the stability of these associations over time. Thus, in this project, we will show that fundamental neural and behavioral processes drive momentary variation in the experience of social isolation and loneliness, and directly impact cardiometabolic health in SMI. In follow-up work, these findings can be used as objective targets in studies of novel interventions which aim to address these major causes of early mortality.