Probiotic Administration for Adolescent Depression

项目摘要/摘要。青春期是抑郁症患病率急剧上升的敏感发育期。我们目前的一线治疗在实现青少年抑郁症的临床缓解方面往往无效。因此，鉴于与青春期抑郁症相关的心理和身体健康状况不佳，迫切需要新的干预措施来治疗这种衰弱的疾病。益生菌是一种由活的有益细菌组成的膳食补充剂，可以改善肠道微生物区系的失调，是治疗青少年抑郁症的一种有前途的疗法。由于目前的益生菌制剂由各种不同的细菌菌株和物种组成，因此科学文献中没有一致的支持使用哪种益生菌，但研究表明，在预防和治疗肠道菌群失调方面，多菌株益生菌可能比单菌株益生菌更有效。因此，主要目标是研究被诊断为临床抑郁症的青少年接受Visbiome®(一种多菌株益生菌)治疗，以确定两个生物学特征的变化：(1)大脑的左侧海马体-楔前(HP)静息状态功能连接(RSFC)和(2)肠道微生物群(驻留在胃肠道的细菌和其他微生物及其遗传物质)中乳杆菌的丰富。中心假说基于肠道-脑轴，肠道微生物群影响海马体和楔前叶，从而导致抑郁症。在已发表的文献和强有力的初步数据的指导下，这一假设将通过在两个随机对照试验(RCT)中研究左侧Hp RSFC、肠道微生物组和抑郁症状的变化来验证。R61阶段将包括77名抑郁青少年，随机分为Visbiome®4500CFU细菌每日两次组或安慰剂每日两次组。R33期将包括77名抑郁症青少年，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。“去/不去标准”：要从R61阶段进展到R33阶段，益生菌组和安慰剂组必须满足以下左Hp RSFC或乳杆菌的效应大小阈值：ηp2≥0.06(p&lt；0.05)。R33阶段还将收集数据，以帮助确定随后更大的疗效试验的最佳益生菌剂量。这项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，该试验可能会改变临床实践或实践指南。这项拟议的研究具有重要意义，因为它有望极大地促进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，最终将为青少年抑郁症的治疗和预防提供信息。

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.