Touched or detached: neurobiological mechanisms of loneliness

感动还是疏远：孤独的神经生物学机制

• 批准号: 509846131
• 负责人: Professor Dr. Valery Grinevich
• 金额: --
• 依托单位: Department of Psychology
• 依托单位国家: 德国
• 项目类别: DIP Programme
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/509846131?language=en
• 关键词: Touched; detached; neurobiological; mechanisms; loneliness

Social isolation is associated with devastating effects on mental and physical health. Emerging evidence related to the effects of the COVID-19 pandemic implicates quarantine-related social isolation as a risk factor for psychiatric disorders. Moreover, even perceived social isolation, termed “loneliness”, increases the risk for coronary heart disease, stroke, depression, cognitive decline and dementia. Therefore, understanding the biological mechanisms underlying the detrimental effects of social isolation will be extremely beneficial and will facilitate the design of interventions that can augment the influence of the limited social interactions experienced by many individuals. Considering that social connectedness is as an innate need, it is likely to involve behavioral, physiological and molecular adaptations. Yet, the neural and hormonal systems that support social connectedness have yet to be identified and described. A central player at the interface of social isolation and connectedness is the hypothalamic neuropeptide oxytocin, the release of which is regulated as a function of social interactions, especially somatosensory stimuli delivered by social touch. This translational project is aimed at probing the behavioral, neural and molecular sequelae of social isolation by carrying out a set of complementary experiments (WPs 1-5) on animal and human models of social isolation. While social isolation includes physical isolation in the animal model (rats), in humans, we will focus on loneliness as a subjective experience of isolation. In rats, we aim to reveal the molecular and neural changes that take place in the brain during social isolation and resocialization by using unbiased transcriptomic and proteomic analyses as well as in vivo electrophysiology at both the system and single cells levels (WP1). Specifically, we aim to reveal anatomical, electrophysiological and molecular modifications induced in the oxytocin system during social isolation and resocialization (WP2). Additionally, we will explore the effects of social isolation at the group level by correlating these modifications across pairs of animals as a proxy for inter-brain coupling. Critically, we will evaluate the possibility of reversing these changes by enhancing endogenous oxytocin system activity using chemogenetic manipulations as well as social touch (WP3). Following these detailed analyses in the rat model, we will explore the effects of loneliness in humans by comparing inter-brain coupling, social connectedness and oxytocin levels of individuals experiencing states of either high or low loneliness (WP4). Specifically, we will take advantage of the high temporal resolution of state-of-the-art dual-functional Near-Infrared Spectroscopy (fNIRS) to examine how inter-brain networks reconfigure during real-life interactions of dyads composed of high loneliness and low loneliness participants.

社会孤立与对身心健康的破坏性影响有关。与COVID-19大流行影响相关的新证据表明，与尼古丁相关的社会隔离是精神疾病的风险因素。此外，即使是被称为“孤独”的社会孤立感，也会增加冠心病、中风、抑郁、认知能力下降和痴呆症的风险。因此，了解社会孤立的有害影响的生物学机制将是非常有益的，并将有助于设计干预措施，可以增加许多人所经历的有限的社会互动的影响。考虑到社会联系是一种天生的需要，它可能涉及行为，生理和分子适应。然而，支持社会联系的神经和荷尔蒙系统尚未被确定和描述。下丘脑神经肽催产素是社会隔离和社会联系界面上的一个核心角色，其释放受社会互动的调节，特别是由社会接触提供的体感刺激。这个翻译项目旨在通过对社会隔离的动物和人类模型进行一系列补充实验（WP 1-5）来探索社会隔离的行为，神经和分子后遗症。虽然在动物模型（大鼠）中，社会隔离包括身体隔离，但在人类中，我们将关注孤独作为隔离的主观体验。在大鼠中，我们的目标是通过使用无偏的转录组学和蛋白质组学分析以及系统和单细胞水平的体内电生理学来揭示在社会隔离和再社会化期间大脑中发生的分子和神经变化（WP 1）。具体来说，我们的目标是揭示社会隔离和再社会化（WP 2）期间催产素系统诱导的解剖学、电生理学和分子修饰。此外，我们将探索社会隔离在群体水平上的影响，通过将这些修改作为脑间耦合的代理在动物对之间进行关联。关键的是，我们将评估逆转这些变化的可能性，通过增强内源性催产素系统的活动，使用化学遗传操作以及社会接触（WP 3）。在大鼠模型中进行这些详细分析之后，我们将通过比较经历高或低孤独状态的个体的脑间耦合，社会联系和催产素水平来探索孤独对人类的影响（WP 4）。具体来说，我们将利用最先进的双功能近红外光谱（fNIRS）的高时间分辨率来研究在由高孤独和低孤独参与者组成的二人组的真实互动过程中，脑间网络如何重新配置。