Neuro-affective response to light in depressed adolescents and young adults

抑郁青少年和年轻人对光的神经情感反应

• 批准号: 10684070
• 负责人: Adriane M. Soehner
• 金额: $ 17.73万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10684070
• 关键词: Acute; Adherence; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Adverse event; Adverse reactions; Affective; Age; Amygdaloid structure; Antidepressive Agents; Auditory; Behavioral; Brain; Cerebrovascular Circulation; Characteristics; Clinical; Clinical Treatment; Corpus striatum structure; Dark Adaptation; Depressed mood; Development; Dose; Early treatment; Enrollment; Exposure to; Female; Functional Magnetic Resonance Imaging; Goals; Individual; Individual Differences; Intervention; Investigational Therapies; Learning; Light; Magnetic Resonance Imaging; Measures; Mental Depression; Modeling; Moods; National Institute of Mental Health; Outcome; Outpatients; Participant; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phototherapy; Physiologic pulse; Pilot Projects; Play; Probability; Process; Protocols documentation; Psychotherapy; Retina; Retinal Ganglion Cells; Rewards; Schedule; Schools; Signal Transduction; Sleep; Structure; System; Testing; Therapeutic; Translating; Treatment Protocols; actigraphy; age difference; age related; antidepressant effect; arterial spin labeling; child depression; cost; diaries; effective intervention; effective therapy; efficacious intervention; eligible participant; experience; high dimensionality; improved; indexing; light effects; melanopsin; mouse model; neuroimaging; novel; personalized medicine; psychosocial; response; side effect; therapy development; young adult

ABSTRACT Adolescent depression is associated with devastating clinical and psychosocial outcomes, and many pediatric depression patients do not respond to existing treatments. With its low cost, minimal side effect profile and efficacy in adult depression, morning bright light therapy (LT) holds promise as a non-medication treatment for adolescent depression. However, maturational differences in the body and brain can alter adolescents’ response to therapeutic doses of adult treatments.Thus, essential first step is to establish whether therapeutic mechanisms underlying antidepressant response to LT in adults translate to adolescents and/or vary with age.Light modulates mood through melanopsin-expressing retinal ganglion cells, which convey light signals from the retina to sub- cortical limbic structures supporting threat (amygdala) and reward (striatum) processing. Antidepressant effects of LT in adults is enhanced by using melanopsin-engaging blue light. Blue-enhanced LT reduces threat-related amygdala activity and increases reward-related striatal activity in healthy adults, and melanopsin-limbic circuits underlie antidepressant effects of light in murine models. Thus, akin to other effective depression treatments, modulation of negative (threat) and positive (reward) neuro-affective mechanisms likely drive clinical benefits of light. Adolescents show higher melanopsin sensitivity to blue light than adults and thus may experience more pronounced effects of blue light on affective brain function. If this notion is supported, it could inform optimized therapeutic dosing of LT for adolescent depression. Light exposures delivered within an MRI scanner engage neuro-affective depression targets in adults, offering an efficient way to probe this therapeutic pathway in adolescence. Using this approach, we propose to test the hypothesis that acute exposure to melanopsin- engaging blue light (vs red light) will stabilize neuro-affective deficits in depressed individuals, and these effects will be stronger for blue light in adolescents than young adults. We will enroll 40 adolescents (12-17yr) and 40 young adults (18-30yr) with depression. As a therapeutic probe, we will examine the direct impact of within- scanner bright light exposures on affective brain function (cerebral blood flow, fMRI). Melanopsin sensitivity will be assessed with pupillometry, and indices of participant developmental, ocular, behavioral and clinical characteristics collected. Our primary aims will test the hypothesis that blue light will stabilize negative (Aim 1: threat) and positive (Aim 2: reward) neuro-affective deficits in depressed participants to a greater extent than red light, and that these effects will vary by developmental stage (adolescent vs adult). Exploratory analyses will 1) examine the extent which melanopic sensitivity explains age differences light-modulated brain function and 2) apply a high-dimensional modeling approach to identify developmental, ocular, behavioral, and clinical features that account for individual differences in neuro-affective engagement by blue light. Understanding the impact of development, and other factors, on therapeutic mechanisms of light will provide an empirical basis for building optimized LTprotocols for adolescent depression,thus increasingefficacy,ease of use, and real-word adherence.

抽象的 青少年抑郁症与毁灭性的临床和社会心理结局有关，许多小儿 抑郁症患者对现有治疗没有反应。其成本低，最小的副作用轮廓和 成人抑郁症的功效，早晨明亮的光疗法（LT）有望作为一种非药物治疗 青春期抑郁症。但是，身体和大脑的成熟差异可以改变青少年的反应 对于成人治疗的治疗剂量。因此，重要的第一步是确定是否具有治疗机制 成人对LT的潜在抗抑郁反应转化为青少年和/或随着年龄的变化。 通过表达黑色素的视网膜神经节细胞的情绪，该细胞从视网膜传达光信号 支持威胁（杏仁核）和奖励（纹状体）处理的皮质边缘结构。抗抑郁作用 通过使用黑色素蛋白启动的蓝光来增强成年人的LT。蓝色增强的LT减少了与威胁有关的 杏仁核活性并增加健康成年人的奖励相关纹状体活性，而黑色素蛋白蛋白 - 纤维蛋白环路电路 光模型中光的抗抑郁作用的基础。类似于其他有效的抑郁疗法， 调节负面（威胁）和阳性（奖励）神经影响机制可能会带来临床益处 光。青少年比成年人表现出对蓝光的敏感性更高，因此可能会经历更多 蓝光对情感大脑功能的明​​显影响。如果支持此概念，它可以告知优化 青少年抑郁症的LT治疗剂量。在MRI扫描仪参与中提供的光线暴露 成人的神经影响抑郁靶标，提供了一种有效的方法来探究这种治疗途径 青少年。使用这种方法，我们建议检验以下假设：急性暴露于黑色素蛋白 - 引人入胜的蓝光（vs红光）将稳定神经影响力定义在抑郁的个体中，这些影响 与年轻人相比，青少年的蓝光对蓝光会很强。我们将注册40名青少年（12-17岁）和40个 年轻人（18-30岁）患有抑郁症。作为治疗探测器，我们将研究内部的直接影响 扫描仪明亮的光暴露于情感大脑功能（脑血流，fMRI）上。黑素蛋白的敏感性会 通过化学计量法评估，参与发育，眼，行为和临床指数 收集的特征。我们的主要目的将检验以下假设：蓝光将稳定负面（AIM 1： 威胁）和积极的（目标2：奖励）神经影响力在抑郁的参与者中比红色更大程度地定义 光线，这些影响会因发展阶段而有所不同（青少年与成人）。探索性分析将1） 检查黑色素敏感性解释年龄差异的程度，脑功能轻度调节，2） 应用高维建模方法来识别发展，眼，行为和临床特征 这解释了蓝光在神经影响参与方面的个体差异。了解 开发和其他因素，基于光机制将为建造提供经验基础 对青少年抑郁症进行了优化的LTProtocols，从而提高了功效，易用性和现实词的依从性。