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

基本信息

批准号：
9766891
负责人：
UMA RAO
金额：
$ 77.87万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9766891
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 Structure 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 sex social symptom treatment tractography treatment guidelines treatment response white matter

项目摘要

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（由申请人提供）：抑郁症是全世界最令人衰弱的疾病之一，其社会和经济负担是一项重大的公共卫生挑战。童年虐待是抑郁症的常见危险因素，当存在时，会进一步损害适应性功能。存在虐待和未受虐待的抑郁症之间存在差异，这表明它们构成了两种不同的表型，并且需要不同的成人遗传和神经生物学研究的初步数据也支持这一观点。本提案的目的是确定患有抑郁症的青少年是否患有抑郁症。与未受虐待的抑郁青少年相比，有虐待史的抑郁青少年在结构和功能上存在明显差异。该研究将重点关注青春期，因为除婴儿期外，这是神经变化和成熟的最大时期，也是虐待对大脑影响的最大时期。在此发育阶段出现的青少年将被招募四组：患有临床抑郁症且有儿童虐待史的青少年、患有临床抑郁症但无虐待史的青少年、无精神疾病但有儿童虐待史的青少年、以及无精神疾病的青少年。紊乱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的宏观和微观结构连接/纤维束描记图谱（特别是负性的额叶边缘回路）。除了识别两种抑郁症之间的群体差异外，他们还将接受静息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的功能连接概况。亚型/表型，我们将评估虐待是否会调节特定抑郁症状特征（例如快感缺失、负面情绪、沉思）的维度评级与神经回路之间的关联，据我们所知，这项研究是第一个利用多模态成像来评估虐待的研究。区分与抑郁症和虐待相结合相关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两个抑郁组之间观察到的差异是否相同。虐待的主要（附加）效应或相互作用效应（即与抑郁症相关的神经特征因虐待而改变）的功能。该研究的结果将增加我们对现有抑郁症神经模型的理解，并有潜力。通过增强治疗指南和算法来区分与两种抑郁症亚型相关的神经标记物，可用于更有效地预测治疗结果，并更有选择性地识别与受害者抑郁症相关的独特神经基质。虐待也将有利于针对那些对当前方法反应不佳的人（如一些临床试验中观察到的那样）开发和测试新疗法。