Mechanistic pathways of the effects of human-animal interaction on depression and psychosocial stress

摘要 抑郁症使人虚弱，代价高昂，而且非常普遍，是导致健康不佳和 全球范围内的残疾。大多数美国家庭都有宠物。宠物提供了一种情感来源 支持和先前的研究表明，它们可能有助于缓解抑郁、焦虑和压力。 然而，建立因果关系或探索机制路径的纵向研究是 还是不够用。这项提案的目标是解决PAR-18-213“人-动物相互作用(HAI)” 这项研究首次纵向考察了宠物在家中对抑郁症的影响 和心理痛苦，并通过研究应激生物标志物来探索潜在的途径 (唾液皮质醇-脱氢表雄酮比率)以及肠道微生物群和 在这些组合中的代谢组。我们将利用三项正在进行的大规模人口研究- 护士健康研究2(NHS2，n=116,430)、NHS3(n=47,435)和今日成长研究 (Guts)，NHS2妇女的12,413个孩子，1996年登记时年龄在9-14岁(88%) 宠物)。通过两年一次的跟踪，他们提供了丰富的重复评估的生活方式，环境， 以及心理社会评估，以便在我们的分析中精细控制它们的潜在混乱性。 我们的主要研究目标包括正在进行的从35,000名参与者的粪便样本收集 NHS2，我们将在收集抑郁症的粪便后对其进行跟踪，包括400名有/没有宠物的女性 和当前应用中的事件抑郁。此外，226名NHS2参与者组成的子队列 (62%的宠物)收集详细的、重复的心理社会评估，包括关于宠物的信息 依恋、宠物主人的个性维度、压力生物标记物以及参与者的肠道 微生物组；因此，我们不需要额外成本就可以利用这些微生物组数据。此外，嵌入在 NHS3，我们将发起一个纵向的‘护士宠物研究’(NPS)，将护士的宠物纳入活动 未来HAI研究的后续行动。 我们的主要假设是，养宠物/依恋宠物可以降低偶发抑郁症的风险， 主要途径包括改善皮质醇-脱氢表雄酮比率和 肠道微生物群的改变，为新的治疗方法和证据提供了可能性- 基于关于将宠物引入家中的建议。

ABSTRACT Depression is debilitating, costly, and highly prevalent, representing the leading cause of ill health and disability worldwide. A majority of US households includes pets. Pets offer a source of emotional support and previous research has shown that they may help ease depression, anxiety, and stress. However, longitudinal studies to establish causal relationships or explore mechanistic pathways are still lacking. The objective of this proposal addressing PAR-18-213, ‘Human-Animal Interaction (HAI) Research’, is to, for the first time longitudinally, examine the effects of pets in the home on depression and psychological distress in humans, and to explore potential pathways by studying stress biomarkers (salivary cortisol-DHEA ratio) and the direct and mediating effects of the gut microbiome and metabolome in these associations. We will leverage three ongoing large population-based studies – the Nurses’ Health Study 2 (NHS2, n=116,430), NHS3 (n=47,435), and the Growing Up Today Study (GUTS), 12,413 children of the NHS2 women, who were 9-14 years old at enrollment in 1996 (88% with pets). With biennial follow-up, they offer a wealth of repeatedly assessed lifestyle, environmental, and psychosocial assessments allowing to finely control for their potential confounding in our analyses. Our primary study aims include an ongoing collection of stool samples from 35,000 participants in the NHS2, who we will follow after stool collection for depression to include 400 women with/without pets and incident depression in the current application. In addition, a subcohort of 226 NHS2 participants (62% with pet) collected detailed, repeated psychosocial assessments including information on pet attachment, pet owner’s personality dimensions, and stress biomarkers as well as participants’ gut microbiome; thus, we leverage these microbiome data at no additional cost. Further, embedded in NHS3, we will initiate a longitudinal ‘Nurses’ Pets Study’ (NPS), enrolling pets of nurses into active follow-up for future HAI studies. Our chief hypotheses are that pet ownership/attachment reduces risk of incident depression and psychological distress, and that primary pathways include an improved cortisol-DHEA ratio and alterations in the gut microbiome, offering the potential for new therapeutic approaches and evidence- based advice regarding the introduction of a pet into one’s home.