Effects of Childhood Maltreatment on Neurocircuitry in Adolescent Depression

童年虐待对青少年抑郁症神经回路的影响

• 批准号: 10237848
• 负责人: UMA RAO
• 金额: $ 77.34万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10237848
• 关键词: Accounting; Address; Adolescence; Adolescent; Adult; Adverse event; Affect; Age; Age of Onset; Algorithms; Amygdaloid structure; Anhedonia; Anisotropy; Behavioral; Biological; Brain; Categories; Characteristics; Child Abuse and Neglect; Clinical; Clinical Trials; Cognitive; Corpus striatum structure; Data; Depressed mood; Development; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Economic Burden; Emotional; Emotions; Ensure; Etiology; Formulation; Functional Magnetic Resonance Imaging; Genetic; Hippocampus (Brain); Individual; Knowledge; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mental Depression; Mental disorders; Motivation; Multimodal Imaging; Neurobiology; Outcome; Participant; Phase; Phenotype; Play; Prefrontal Cortex; Process; Public Health; Race; Recording of previous events; Rest; Rewards; Risk Factors; Role; Sampling; Shapes; Socioeconomic Status; Stress; Subgroup; Symptoms; Testing; Theoretical model; Treatment outcome; Ventral Striatum; abuse neglect; base; child depression; clinical practice; cohesion; depression model; depressive symptoms; design; disability; disorder risk; disorder subtype; experience; gray matter; imaging study; improved; indexing; infancy; maltreatment; negative affect; negative mood; neglect; neural circuit; neural model; neural network; neuroimaging; positive emotional state; public health relevance; recruit; relating to nervous system; response; reward processing; rumination; sex; social; symptom treatment; tractography; treatment guidelines; treatment response; white matter

 DESCRIPTION (provided by applicant): Depression is one of the most debilitating diseases worldwide, and the social and economic burden is a major public health challenge. Childhood maltreatment is a common risk factor for depression and when present further compromises adaptive functioning. Important clinical differences exist between depression with and without maltreatment, suggesting that they constitute two distinct phenotypes and require different treatment guidelines. Preliminary data from genetic and neurobiological studies in adults also support this notion. The aim of this proposal is to determine whether adolescents with depression and a history of maltreatment have distinct differences in structural and functional neural circuits compared to depressed adolescents without maltreatment. The study will focus on adolescence because, except for infancy, it is the greatest period of neural change and maturation, and the effects of maltreatment on the brain appear during this developmental stage. Four groups will be recruited: adolescents with clinical depression and a history of childhood maltreatment, adolescents with clinical depression and no maltreatment history, adolescents with no psychiatric disorder but have a history of childhood maltreatment, and adolescents with no psychiatric disorder or maltreatment history. The participants will undergo structural magnetic resonance imaging and diffusion tensor imaging studies to measure macro- and micro-structural connectivity/tractography profiles in key neural networks that are associated with core symptoms of depression (specifically the fronto-limbic circuit for negative mood and the fronto-striatal circuit for anhedonia). They will undergo resting-state and task-based functional magnetic resonance imaging studies to measure functional connectivity profiles in these neural networks. In addition to identifying group differences between the two depression subtypes/phenotypes, we will assess whether maltreatment moderates the associations between dimensional ratings of specific depressive symptom profiles (e.g., anhedonia, negative affect, rumination) and neural circuits. To our knowledge, this study is the first to utilize multi-modal imaging to differentiate structural and functional neural substrates associated with the combination of depression and maltreatment relative to those associated with depression. The four group (2 x 2) design will enable us to determine if the observed differences between the two depressed groups are a function of a main (additive) effect of maltreatment or an interaction effect (i.e., the neural characteristics associated with depression are altered by maltreatment). The results of the study will increase our understanding of the existing neural models of depression and have the potential to improve clinical practice by enhancing treatment guidelines and algorithms. Differentiation of the neural markers associated with the two depression subtypes could be used to predict treatment outcome more effectively and to more selectively index clinical responses to treatment. Identifying the unique neural substrates associated with depression in victims of maltreatment would also facilitate the development and testing of new treatments for those who do not respond well to current approaches (as observed in some clinical trials).

 描述(申请人提供)：抑郁症是世界上最令人衰弱的疾病之一，社会和经济负担是一个重大的公共卫生挑战。童年虐待是抑郁症的常见危险因素，一旦出现，就会进一步损害适应功能。伴和不伴虐待的抑郁症之间存在着重要的临床差异，这表明它们构成了两种不同的表型，需要不同的治疗指南。来自成人遗传和神经生物学研究的初步数据也支持这一观点。这项建议的目的是确定有抑郁症和虐待史的青少年与没有虐待的抑郁症青少年相比，在结构和功能神经回路方面是否有明显的差异。这项研究将重点放在青春期，因为除婴儿期外，青春期是神经变化和成熟的最大时期，而虐待对大脑的影响出现在这个发育阶段。将招募四组：有临床抑郁症和儿童期虐待史的青少年，有临床抑郁症和无虐待史的青少年，没有精神障碍但有儿童期虐待史的青少年，以及没有精神障碍或虐待史的青少年。参与者将接受结构磁共振成像和扩散张量成像研究，以测量与抑郁症核心症状相关的关键神经网络中的宏观和微观结构连通性/气管造影术图谱(特别是用于负面情绪的额缘回路和用于快感缺乏的额纹状体回路)。他们将接受静息状态和基于任务的功能磁共振成像研究，以测量这些神经网络中的功能连接概况。除了确定两种抑郁亚型/表型之间的群体差异外，我们还将评估虐待是否缓和了特定抑郁症状特征(例如，快感缺乏、消极情绪、沉思)的维度评级与神经回路之间的关联。据我们所知，这项研究是第一次利用多模式成像来区分与抑郁症和虐待相结合的结构和功能神经基质与与抑郁症相关的神经基质。四组(2 X 2)设计将使我们能够确定观察到的两个抑郁组之间的差异是虐待的主要(相加)效应的函数还是交互作用的函数(即，与抑郁症相关的神经特征因虐待而改变)。这项研究的结果将增加我们对现有抑郁症神经模型的理解，并有可能通过改进治疗指南和算法来改进临床实践。区分与这两种抑郁亚型相关的神经标志物可以更有效地预测治疗结果，并更有选择性地指示临床对治疗的反应。确定与虐待受害者的抑郁症有关的独特神经底物也将有助于为那些对当前方法反应不佳的人开发和测试新的治疗方法(正如在一些临床试验中所观察到的那样)。