Estracellular Vesicles as Non-Invasive Predictors of Antidepressant Outcomes in Pediatric Anxiety

雌细胞囊泡作为小儿焦虑抗抑郁结果的非侵入性预测因子

• 批准号: 9979926
• 负责人: Jeffrey Robert Strawn
• 金额: $ 48.76万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-17 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9979926
• 关键词: Adolescence; Adolescent; Adult; Adverse effects; Affect; Age; Agitation; Antidepressive Agents; Anxiety Disorders; Biologic Characteristic; Biological; Biological Markers; Cells; Central Nervous System Diseases; Ceramides; Child; Childhood; Clinical; Collection; DSM-V; Data; Development; Disease; Disinhibition; Distal; Dose; Emotional; Escitalopram; Event; Family; Goals; Health; Hyperactive behavior; Impairment; Impulsivity; Intervention; Left; Lipids; Major Depressive Disorder; Measurement; Mental Health; Mental disorders; Methods; MicroRNAs; Molecular; Neural Cell Adhesion Molecule L1; Neurons; Organelles; Outcome; Patients; Pharmaceutical Preparations; Phosphatidylethanolamine; Phosphatidylinositols; Phosphatidylserines; Physiological Processes; Placebos; Plasma; Plasmalogens; Predictive Value; Prevalence; Process; Proteins; RNA; Randomized; Safety; Selection for Treatments; Selective Serotonin Reuptake Inhibitor; Separation Anxiety; Sertraline; Signal Transduction; Site; Sleeplessness; Social Anxiety Disorder; Symptoms; System; Testing; Time; Titrations; Vesicle; Youth; anxious; base; childhood anxiety; dihydroceramide; double-blind placebo controlled trial; extracellular; extracellular vesicles; flexibility; gastrointestinal; gastrointestinal symptom; generalized anxiety; impression; multiple omics; novel; open label; pediatric patients; precision medicine; predictive marker; predictive signature; prospective; psychopharmacologic; psychosocial; randomized trial; response; side effect; social; success; treatment of anxiety disorders; treatment response; week trial

PROJECT SUMMARY Anxiety disorders are among the most common psychiatric conditions in children and adolescents with a prevalence of more than 10%. Left untreated, pediatric patients with anxiety disorders suffer physical, emotional, academic, and social impairment, and these disorders increase the likelihood of secondary anxiety disorders, major depressive disorder and other psychiatric conditions in adulthood. Selective-serotonin reuptake inhibitors (SSRIs) are the first-line psychopharmacologic treatment for these conditions, but may take up to 8 weeks to produce responses—which only occur in 50-60% of youth. Further, SSRI-related adverse effects emerge early in the course of treatment, decrease the likelihood of success and increase the likelihood of medication discontinuation. These significant side effects include gastrointestinal symptoms and activation—a hyperarousal event characterized by specific symptoms including an increase in activity, impulsivity, disinhibition, restlessness, and insomnia. Today, there is no way to predict, based on clinical or biological characteristics which children and adolescents will respond to an SSRI or who will develop treatment-limiting adverse effects—a significant concern of patients and their families. The goal of this proposal is to advance the treatment of pediatric anxiety disorders by examining predictive markers of SSRI treatment response and SSRI-related gastrointestinal symptoms and activation. This proposal builds upon our significant finding that 5 lipid classes derived from plasma extracellular vesicles (EVs) predict SSRI response in anxious youth. This application proposes to replicate our preliminary study in a large, multi- site, double-blind placebo-controlled trial and utilizes synchronized methods for biospecimen collection and outcome measurement. This proposal will also evaluate a specific subpopulation of EVs—L1CAM(+) EVs— which are enriched in cargoes of neuronal origin, providing a targeted, non-invasive assessment of the molecular milieu of the CNS. The line of inquiry is novel to precision medicine/child and adolescent mental health, and has the potential to propel the treatment of anxiety disorders in youth while increasing the safety of SSRI treatment, by predicting SSRI-related side effects.

项目摘要 焦虑症是儿童和青少年中最常见的精神疾病之一， 发病率超过10%。如果不进行治疗，患有焦虑症的儿科患者将遭受身体，情感， 学业和社交障碍，这些障碍增加了继发性焦虑症的可能性， 成年后的严重抑郁症和其他精神疾病。选择性5-羟色胺再摄取抑制剂 （SSRIs）是这些疾病的一线精神药理学治疗，但可能需要长达8周的时间， 只有50 - 60%的年轻人会有这种反应。此外，SSRI相关的不良反应出现早 在治疗过程中，减少成功的可能性，增加药物治疗的可能性 中止。这些显著的副作用包括胃肠道症状和激活-一种过度觉醒 以特定症状为特征的事件，包括活动增加、冲动、抑制解除、烦躁不安， 还有失眠 今天，没有办法预测，根据临床或生物学特征，儿童和青少年 将对SSRI有反应或将出现治疗限制性不良反应-患者的一个重要问题 和他们的家人 该提案的目标是通过检查预测性焦虑症， SSRI治疗反应和SSRI相关胃肠道症状和激活的标志物。这项建议 基于我们的重要发现，5类脂质来源于血浆细胞外囊泡（EV）预测 焦虑青年的SSRI反应本申请建议在一个大型、多- 研究中心、双盲安慰剂对照试验，采用同步方法进行生物标本采集， 结果测量。本提案还将评价EVs-L1CAM（+）EV的特定亚群- 其富含神经元来源的货物，提供了针对性的、非侵入性的分子评估， CNS的环境。 这一调查路线对精准医学/儿童和青少年心理健康来说是新颖的，并有可能 通过预测，在提高SSRI治疗安全性的同时， SSRI相关的副作用