Supplement: Neurobehavioral mechanisms of social isolation and loneliness in serious mental illness

补充：严重精神疾病中社会孤立和孤独的神经行为机制

• 批准号: 10615480
• 负责人: DANIEL C FULFORD
• 金额: $ 3.72万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615480
• 关键词: Address; Basal Ganglia; Behavioral; Cellular Phone; Early Diagnosis; Health; Individual; Individual Differences; Intervention; Life; Link; Loneliness; Measures; Medial; Modeling; Motivation; Outcome; Phenotype; Process; Quality of life; Research; Rewards; Social Perception; Social isolation; Stimulus; Temporal Lobe; Testing; Time; Variant; Work; behavior prediction; cardiometabolism; design; digital assessment; experience; follow-up; improved; indexing; mortality; neural; neural correlate; neurobehavioral; neuroimaging; new therapeutic target; novel; novel strategies; prevent; psychologic; response; severe mental illness; smartphone based assessment; social; social contact

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.

概括 严重精神疾病 (SMI) 的一些最令人衰弱和有害的方面是 1) 社会孤立 （社交接触次数少）和 2）社交脱节（孤独感）的主观体验 经常伴随这些情况。社会孤立和孤独感极大地影响了日常功能和 与 SMI 心脏代谢健康状况不佳和早期死亡有关，目前尚无可用的方法 可以预防或扭转这些疾病造成的破坏性后果的治疗方法。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，以及 人们对它们如何影响健康结果知之甚少。然而，最近的研究线索 先进的神经影像和数字评估已成为一种新颖的调查方法的基础 本提案概述了此类机制。先前的研究表明，客观的孤立和孤独是 相关但又有些独立。最近的神经影像学研究结果支持了这一模型，表明 社会孤立和孤独既有共同的又有不同的神经关联。然而，同样清楚的是，这些 不是静态现象；基于智能手机的评估揭示了社会瞬息万变的动态变化 孤立和孤独。预期拒绝的个体差异与瞬时性有关。 经历孤独、更多的回避以及随之而来的社会孤立感的增加。因此，在当前 应用中，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，以及这些经历的每时每刻的变化，在 60 患有 SMI 的个体和 60 名对照受试者。在拟议项目的目标 1 中，我们将表明更高的水平 SMI 中的社会孤立和孤独感与对社会刺激的共同且独特的神经反应有关， 与社会孤立相关的社会感知相关回路（内侧颞叶区域）的反应不足， 与孤独相关的奖励相关回路（基底神经节区域）的反应不足。在目标 2 中，我们将 通过智能手机评估，使用纵向测量来衡量社会孤立和孤独感的短暂变化 “爆裂”设计。最后，在目标 3 中，我们将确定社会孤立和孤独感的定量标记如何 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 随着时间的推移。因此，在这个项目中，我们将证明基本的神经和行为过程驱动瞬时 社会隔离和孤独感的变化，并直接影响 SMI 的心脏代谢健康。 在后续工作中，这些发现可以作为新颖干预措施研究的客观目标，旨在 解决这些早期死亡的主要原因。