Neurodevelopmental profiles related to transdiagnostic and disorder-specific symptoms of anxiety and depression

项目摘要 近40%的青少年患有焦虑症或重度抑郁症。这些疾病通常首先 这些问题在青春期出现，其不良后果往往持续到成年。因此，在本发明中， 青春期是理解与这些相关的生物学途径的关键发展时期。 紊乱评分者间的信度和区分度差的焦虑和抑郁障碍一直是一个主要的 NIMH RDoC框架中的一个因素，强调需要研究大脑过程的配对措施 精神病学的维度方法根据这一框架， K99/R00 Pathway to Independence Award是为申请人提供必要的培训， 与焦虑和抑郁的共同症状相关的不同发育神经特征 （痛苦），以及与焦虑的障碍特异性症状（焦虑）相关的神经特征 抑郁症（低积极影响）。此外，申请人将需要遗传学培训， 成功地实现了量化遗传影响与独特环境影响的相对贡献的目标。 对焦虑和抑郁情绪相关神经特征的影响。为了实现这样 目标，申请人将获得无与伦比的指导专家在精神病理学，遗传学， 先进的神经影像学方法（Drs. D。Barch，N. Dosenbach，A.作者：J. Agrawal，J. Constantino，J.吕比，C. 西尔维斯特和D.格林），并将获得一流的临床，成像和招聘资源， 华盛顿大学。拟议的培训计划将使申请人实现几个短期 必要的目标，以促进他的长期目标，成为一个独立的调查员在一个研究-I 大学，包括精神病理学和遗传学的新培训（双胞胎设计）。这些培训目标将是 通过拟议的研究。首先，临床数据和功能连接（FC）MRI数据， 大型青少年大脑和认知发展（ABCD）样本（n = 11，875）将用于识别和 复制与焦虑的转诊断和疾病特异性症状相关的神经特征（生物型） 抑郁症（Aim 1）将利用该数据集的子集（ABCD双胞胎数据集; n = 800对双胞胎）， 评估这些生物型/症状关系的遗传性（目标2.1）。利用FC的最新进展 MRI数据采集能够可靠地量化个体水平FC（精确功能标测）， 申请人将量化遗传对生物型/症状关系的独特环境影响， 指向潜在的独特因果途径和独特干预途径（目标2.2）。特别是 所提出的方法可以扩展到其他发育性神经精神障碍， 早期个体化治疗干预。通过一个研究项目， 技术和分析方法来询问与焦虑和抑郁有关的症状的生物标志物， 申请人将继续在他的独立职业生涯中解决与NIMH相关的研究问题。

PROJECT ABSTRACT Nearly 40% of adolescents suffer from an anxiety disorder or major depression. These disorders usually first emerge during adolescence, and the adverse consequences of them often persist into adulthood. As such, adolescence is a critical developmental period for understanding the biological pathways related to these disorders. Poor inter-rater reliability and discriminability of anxiety and depressive disorders has been a major factor in the NIMH RDoC framework emphasizing the need for studies pairing measures of brain processes with dimensional approaches to psychiatric symptomatology. In line with this framework, the goal of this K99/R00 Pathway to Independence Award is to provide the applicant with the training necessary to identify distinct developmental neural features that are related to shared symptoms across anxiety and depression (distress), as well as neural features that are related to disorder-specific symptoms of anxiety (anxious apprehension) and depression (low positive affect). Furthermore, the applicant will require genetics training to succeed in the goal of quantifying the relative contribution of genetic influence vs. unique environmental influence on the neural features related to anxiety and depression symptomatology. In order to achieve such goals, the applicant will receive unparalleled mentorship by experts in psychopathology, genetics, and advanced neuroimaging methodologies (Drs. D. Barch, N. Dosenbach, A. Agrawal, J. Constantino, J. Luby, C. Sylvester, and D. Greene) and will have access to superb clinical, imaging, and recruitment resources at Washington University. The proposed training plan will enable the applicant to achieve several short-term goals necessary to facilitate his long-term goal of becoming an independent investigator at a Research-I University, including new training in psychopathology and genetics (twin designs). These training goals will be advanced through the proposed research. First, clinical data and functional connectivity (FC) MRI data within the large Adolescent Brain and Cognitive Development (ABCD) sample (n=11,875) will be used to identify and replicate the neural signatures (biotypes) related to transdiagnostic and disorder-specific symptoms of anxiety and depression (Aim 1). A subset of this dataset (ABCD twin dataset; n=800 twin pairs) will be leveraged to assess the heritability of these biotype/symptom relationships (Aim 2.1). Capitalizing on recent advances in FC MRI data acquisition enabling reliable quantification of individual-level FC (precision functional mapping), the applicant will quantify the genetic vs. unique environmental influence on biotype/symptom relationships, pointing towards potential unique causal pathways and unique intervention pathways (Aim 2.2). Notably, the proposed methods can be extended to other developmental neuropsychiatric disorders, setting the stage for early individualized treatment intervention. With a research program that employs multiple converging techniques and analysis methods to interrogate biomarkers of symptoms related to anxiety and depression, the applicant will continue to address research questions relevant to the NIMH throughout his independent career.