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.

项目总结/摘要。青春期是抑郁症的敏感发育期，抑郁症的患病率急剧上升。我们目前的一线治疗在青少年抑郁症的临床缓解方面往往无效。因此，鉴于与抑郁症相关的不良心理和身体健康结果，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生态失调，是治疗青少年抑郁症的一种有希望的方法。虽然在科学文献中没有达成共识，因为目前的益生菌制剂由各种不同的细菌菌株和物种组成，但研究表明，多菌株益生菌可能比单菌株益生菌更有效地预防和治疗肠道生态失调。因此，主要目标是研究接受Visbiome®（一种多菌株益生菌）治疗的诊断为临床抑郁症的青少年，以确定两种生物特征的变化：（1）大脑的左前丘-楔前叶（HP）静息状态功能连接（RSFC）和（2）肠道微生物组的乳酸杆菌丰度（细菌和其他微生物及其存在于胃肠道中的遗传物质）。核心假设是基于肠-脑轴，其中肠道微生物组影响海马和楔前叶，从而影响抑郁症。在已发表文献和强有力的初步数据的指导下，将通过研究两项随机对照试验（RCT）中左HP RSFC，肠道微生物组和抑郁症状的变化来验证这一假设。R61阶段将由77名抑郁症青少年组成，他们被随机分配到Visbiome® 4500亿CFU细菌每日两次组或安慰剂每日两次组。R33阶段将由77名抑郁症青少年组成，随机分为三组：（1）Visbiome® 4500亿CFU细菌每日两次，（2）Visbiome® 9000亿CFU细菌每日两次，或（3）安慰剂每日两次组。“通过/不通过标准”：为了从R61期推进到R33期，益生菌组相对于安慰剂组必须满足左HP RSFC或乳酸杆菌的以下效应量阈值：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，用于后续更大的疗效试验。拟议的研究是创新的，因为它将为未来疗效试验的设计提供信息，该试验有可能改变临床实践或实践指南。这项拟议的研究意义重大，因为它有望大大提高我们对益生菌改善青少年抑郁症状的潜在机制的认识和理解，这将最终为青少年抑郁症的治疗和预防提供信息。