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

摘要 严重精神疾病(SMI)最令人衰弱和有害的一些方面是社交孤立 (社交次数少)和2)社交脱节的主观体验(孤独感) 经常伴随这些情况。社会孤立和孤独极大地影响日常运作和 与心脏代谢健康不良和重度心肌梗死早期死亡率有关，目前还没有可用的 可以预防或扭转这些疾病的破坏性后果的治疗。这可能是 部分原因是社交孤立和孤独背后的神经和心理机制，以及 它们如何影响健康结果，人们知之甚少。然而，最近通过研究发现的线索 先进的神经成像和数字评估已经形成了一种新的研究方法的基础 这种机制，在本提案中概述。先前的研究表明，客观的孤立和孤独是 相互关联，但也有一定的独立性。最近的神经成像发现支持这一模型，揭示了 社交孤立和孤独既有共同的，也有不同的神经关联。然而，也很明显，这些 不是静态的现象；基于智能手机的评估揭示了社交网络的短暂、动态变化 与世隔绝和孤独。被拒绝预期的个体差异与瞬间相关 孤独的经历，更多的回避，以及随后的社交孤立增加。因此，在当前 应用，我们建议综合测量相对稳定的神经和行为预测因子 社会孤立和孤独，以及这些经历中的时刻变化，在60% SMI患者和60名对照组。在拟议项目的目标1中，我们将表明更高的水平 SMI中的社交孤立和孤独与对社会刺激的共同和独特的神经反应有关， 与社会隔离有关的社会知觉相关回路(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(基底节区域)的反应不足。在目标2中，我们将 使用纵向的智能手机评估来衡量社交孤立和孤独感的短暂变化 “爆裂”设计。最后，在目标3中，我们将确定社交孤立和孤独的量化标记物 在目标1和目标2中确定的预测心脏代谢健康的指数，测量这些关联的稳定性 随着时间的推移。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间 在SMI中，社交孤立和孤独体验的变化，并直接影响心脏代谢健康。 在后续工作中，这些发现可作为研究新干预措施的客观目标，目的是 解决这些导致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.