Probiotic Administration for Adolescent Depression

益生菌治疗青少年抑郁症

• 批准号: 10646130
• 负责人: Cherry Leung
• 金额: $ 56.48万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646130
• 关键词: 15 year old; Adherence; Adolescence; Adolescent; Adult; Affect; Age; Bacteria; Beck depression inventory; Biological; Brain; Clinical; Consensus; Data; Depressed mood; Depressive disorder; Development; Diagnosis; Dose; Exhibits; Female; Formulation; Functional Magnetic Resonance Imaging; Future; Gastrointestinal tract structure; Genetic Materials; Hippocampus; Hydrocortisone; Intake; Intervention; Knowledge; Lactobacillus; Left; Literature; Measures; Mediating; Mental Depression; Mental Health; Methods; Neurosecretory Systems; Outcome; Pathway interactions; Patients; Phase; Placebos; Practice Guidelines; Predisposition; Prevalence; Prevention; Probiotics; Public Health; Publishing; Randomized; Randomized, Controlled Trials; Reporting; Research; Rest; Safety; Severities; Testing; Youth; adolescent-onset depression; child depression; clinical diagnosis; clinical practice; clinical remission; depressed patient; depressive symptoms; design; dietary supplements; disability; efficacy trial; gut dysbiosis; gut microbiome; gut microbiota; gut-brain axis; hypothalamic-pituitary-adrenal axis; improved; innovation; insight; male; microbiota; microorganism; physical conditioning; placebo group; prevent; probiotic therapy; recruit; timeline; treatment comparison; treatment group

PROJECT SUMMARY/ABSTRACT. Adolescence is a sensitive developmental period in which prevalence rates of depression sharply increase. Our current first-line treatments are often ineffective in achieving clinical remission in adolescents with depression. Thus, given the poor mental and physical health outcomes associated with adolescent-onset depression, new interventions are urgently needed for the treatment of this debilitating condition. Probiotics, dietary supplements consisting of live beneficial bacteria that can improve dysbiosis of the gut microbiota, are a promising treatment for adolescent depression. While there is no consensus in the scientific literature supporting which probiotic to administer since current probiotic formulations consist of various different bacterial strains and species, research suggests that multi-strain probiotics may be more efficacious than single-strain probiotics in preventing and treating gut dysbiosis. Therefore, the primary objective is to study adolescents diagnosed with a clinical depressive disorder undergoing Visbiome®, a multi-strain probiotic, treatment to determine changes in two biological signatures: (1) the left hippocampus–precuneus (HP) resting-state functional connectivity (RSFC) of the brain and (2) Lactobacillus abundance of the gut microbiome (bacteria and other microorganisms and their genetic materials that reside in the gastrointestinal tract). The central hypothesis is based on the gut-brain axis, where the gut microbiome influences the hippocampus and precuneus, and thus depression. Guided by published literature and strong preliminary data, this hypothesis will be tested by studying changes in the left HP RSFC, gut microbiome, and depressive symptoms in two randomized controlled trials (RCTs). The R61 phase will consist of 77 depressed adolescents randomized to either Visbiome® 450 billion CFU bacteria twice daily group or placebo twice daily group. The R33 phase will consist of 77 depressed adolescents randomized to one of three groups: (1) Visbiome® 450 billion CFU bacteria twice daily, (2) Visbiome® 900 billion CFU bacteria twice daily, or (3) placebo twice daily group. “Go/No-Go Criterion”: To advance from the R61 to R33 phase, the probiotic group vs. placebo group must meet the following effect size threshold for either the left HP RSFC or Lactobacillus: ηp2 ≥ 0.06 (p<0.05). The R33 phase will also collect data to help determine the optimal dose of probiotics for a subsequent larger efficacy trial. The proposed research is innovative because it will inform the design of a future efficacy trial that has the potential to change clinical practice or practice guidelines. The proposed research is significant since it is expected to greatly advance our knowledge and understanding of the underlying mechanism by which probiotics improve depressive symptoms in adolescents, which will ultimately inform the treatment and prevention of adolescent depression.

项目摘要/摘要：青春期是一个敏感的发育时期，抑郁症的患病率急剧上升，因此，考虑到与抑郁症相关的不良心理和身体健康结果，我们目前的一线治疗通常无法有效地实现抑郁症的临床缓解。青少年发病的抑郁症，迫切需要新的干预措施来治疗这种使人衰弱的疾病。益生菌是由活的有益细菌组成的膳食补充剂，可以改善肠道微生物群的失调，是治疗青少年的一种有前途的治疗方法。由于目前的益生菌配方由各种不同的细菌菌株和物种组成，因此科学文献中对于使用哪种益生菌尚未达成共识，但研究表明，多菌株益生菌在预防和治疗肠道方面可能比单菌株益生菌更有效。因此，主要目标是研究被诊断患有临床抑郁症的青少年接受 Visbiome®（一种多菌株益生菌）治疗，以确定两个生物特征的变化：(1) 左侧。中心假设基于大脑的海马-楔前叶 (HP) 静息态功能连接 (RSFC) 和 (2) 肠道微生物组的乳酸菌丰度（细菌和其他微生物及其遗传物质）。在已发表的文献和强有力的初步数据的指导下，这一假设将通过研究得到检验。两项随机对照试验 (RCT) 中左 HP RSFC、肠道微生物组和抑郁症状的变化 R61 阶段将由 77 名抑郁青少年组成，随机分为 Visbiome® 4500 亿 CFU 细菌每天两次组或安慰剂 R33 组。该阶段将由 77 名抑郁症青少年组成，随机分为三组之一：(1) Visbiome® 4500 亿 CFU 细菌，每天两次，(2) Visbiome® 9000 亿 CFU 细菌每天两次，或 (3) 安慰剂每天两次“通过/不通过标准”：为了从 R61 阶段进入 R33 阶段，益生菌组与安慰剂组必须满足以下任一效果大小阈值。左侧 HP RSFC 或乳酸菌：ηp2 ≥ 0.06 (p<0.05) R33 阶段还将收集数据，以帮助确定益生菌的最佳剂量，以实现后续更大的功效。拟议的研究具有创新性，因为它将为未来疗效试验的设计提供信息，而该试验有可能改变临床实践或实践指南。拟议的研究意义重大，因为它有望大大提高我们对潜在机制的认识和理解。益生菌可以改善青少年的抑郁症状，最终将为青少年抑郁症的治疗和预防提供信息。