Adolescent Brain Bases of Intergenerational Risk for Depression

项目摘要 青春期是理解重度抑郁症（MDD）的关键时期，因为近一半的生命 精神疾病的诊断开始于14岁。此外，抑郁症的代际风险（风险;有 父母中有抑郁症的人）会使青少年患抑郁症的可能性增加三到五倍。这个目标 研究的目的是了解与风险相关的青少年神经因素， 风险青少年的神经发育路径。这项拟议中的研究增加了正在进行的NIMH拨款 （U 01 MH 108168）比较了患有MDD的青少年（14-15岁）和 无MDD/MDD代际风险的青少年（CON）。我提议增加一个新的青少年群体 谁是在抑郁症的代际风险（风险），以解决以下目标。首先，我的目标是 青少年MDD的风险（特征）和临床诊断（状态）之间的功能和结构神经差异。 我将招募并描述120名年龄和性别匹配的青少年（14-15岁）： 抑郁症，但没有个人病史的MDD（风险），40名青少年没有风险和没有MDD的历史 (CON)和40名患有MDD的青少年。我将进行功能性磁共振成像（fMRI）， (b)结构MRI（sMRI）和（c）扩散MRI（dMRI）。第二，我的目标是发现神经发育 与风险相关的差异。两年后，我将重新描述和重新扫描风险和CON青少年， 初始扫描我将评估RISK和CON在功能和结构神经发育方面的差异 青少年在这两年里。我还将评估与风险相关的 脑功能和结构的神经发育变化与抑郁症的发展有关 症状第三，我的目标是发现多模式基线测量是否能预测抑郁症的进展。 风险青少年的症状。所有120名青少年将接受广泛的临床和神经表征 在研究入组时，并将在研究后两年每6个月接受一次随访临床检查， 招生我将确定是否行为和/或大脑的措施，在登记预测随后的 在这两年里抑郁症状的发展。这项研究将是第一个：1） 分离RISK，MDD和CON青少年之间的功能和结构脑差异，2）确定 与CON青少年相比，RISK的神经发育变化，以及3）提供精确的生物学 预测高危青少年抑郁症的发展。从这件事中获得的知识 这项研究将提供一个新的理解的神经基础的风险和发达的抑郁症， 青少年，以及提供宝贵的贡献，早期预防MDD。

Project Summary Adolescence is a critical time for understanding Major Depressive Disorder (MDD) because nearly half of lifetime diagnoses of psychiatric disorders begin by age 14. Further, intergenerational risk for depression (RISK; having a parent with MDD) increases adolescent likelihood of developing MDD by three- to five-fold. The goal of this research is to understand adolescent neural factors associated with RISK and to characterize the neurodevelopmental path of RISK adolescents. The proposed research adds to an ongoing NIMH grant (U01MH108168) that compares brain function and structure between adolescents (ages 14-15) with MDD and adolescents without MDD/intergenerational risk for MDD (CON). I propose to add a new group of adolescents who are at intergenerational risk for depression (RISK) to address the following aims. First, I aim to dissociate functional and structural neural differences between risk (traits) and clinical diagnosis (state) of adolescent MDD. I will recruit and characterize 120 age- and sex-matched adolescents (ages 14-15): 40 adolescents at RISK for depression but without a personal history of MDD (RISK), 40 adolescents without RISK and no history of MDD (CON), and 40 adolescents with current MDD. I will perform (a) functional magnetic resonance imaging (fMRI), (b) structural MRI (sMRI), and (c) diffusion MRI (dMRI). Second, I aim to discover neurodevelopmental differences associated with RISK. I will re-characterize and re-scan RISK and CON adolescents two years after initial scanning. I will assess differences in functional and structural neurodevelopment between RISK and CON adolescents over this two-year period. I will also assess the extent to which RISK-associated neurodevelopmental changes in brain function and structure are related to development of depressive symptoms. Third, I aim to discover whether multimodal baseline measures predict progression of depressive symptoms in RISK adolescents. All 120 adolescents will undergo extensive clinical and neural characterization at study enrollment, and will undergo follow-up clinical examinations every six months for two years post- enrollment. I will determine whether behavioral and/or brain measures at enrollment predict the subsequent progression of depressive symptoms over this two-year period. The proposed research would be the first to: 1) dissociate functional and structural brain differences between RISK, MDD, and CON adolescents, 2) determine neurodevelopmental changes in RISK compared to CON adolescents, and 3) provide precise biological prediction of the development of depressive symptomology in at-risk adolescents. Knowledge gained from this study will provide a new understanding of the neural underpinning of both risk and developed depression in adolescence, as well as provide valuable contribution toward early prevention of MDD.