Replicability, Mechanisms, and Trajectory of Neural Alterations Related to General Psychopathology

项目摘要/摘要 精神疾病的高发病率(约50%的成年人)对心理健康研究和 练习一下。积累的心理健康研究鼓励将重点转移到跨诊断维度 由于难以识别病因、生物标记物和 针对个别疾病的特异性治疗。为了支持这一转变，跨诊断研究发现 一种常见的精神病理因素--通常被称为‘p’因素--它解释了 在不同的样本中内化、外化和思维障碍。确定这一一般情况的神经关联 精神病理学因素将证实其在表征精神障碍共同起源方面的重要性。 并帮助我们开始了解p因子可能导致风险的机制。上一首 申请人的研究已经确定了p因子和a中的结构变化之间的关系。 小脑-丘脑-皮质环路(CTCC)，参与高级认知和情绪加工。一台F32 博士后奖学金将允许申请者通过检查可复制性来批判性地扩展这项研究， CTCC神经改变与p因子得分之间的关系的机制和轨迹， 公开可用的现有数据集：神经精神病学表现学联盟(CNP)和青少年 脑与认知发展(ABCD)研究。CNP包括健康成人和患者(21-50岁) 患有注意力缺陷/多动障碍、双相情感障碍和精神分裂症。Check Alignment of PHs>JOU JOU包括一个全国性的 被纵向跟踪了10年的具有代表性的青年样本(9-10岁)。使用来自 这两项研究将允许申请者(1)检查p因素分数和 CTCC改变可在青年、大多数重大精神疾病(ABCD)发作之前和在 严重精神疾病患者(CNP)，(2)测试这种联系的神经认知机制，以及 (3)追踪与这些神经改变有关的症状随时间的演变。此外，申请者将 在健康的年轻人中进行可行性研究，以了解如何在认知过程中可靠地激活CTCC 控制任务，并为未来的拨款提供试点数据。有大量的研究和培训机会 在麦克莱恩医院/哈佛医学院，领导Diego Pizzagalli博士(主要导师)的指导 在抑郁症的临床神经科学领域，以及罗曼·科托夫博士(统计学专家)的咨询 精神症状建模)和布莱斯·弗雷德里克博士(磁共振成像物理学专家)， 申请者将接受MRI实验设计和分析、统计建模等各方面的培训 随着时间的推移症状的结构和轨迹，专业发展技能，以及设计和 实施她的第一项独立功能核磁共振(FMRI)研究。总之，拟议的培训计划将支持 对跨诊断神经科学研究做出贡献的申请人，在统计建模方面的磨练技能和 先进的神经成像研究，并建立独立研究计划。

Project Summary/Abstract High rates of psychiatric comorbidity (~50% of adults) pose significant challenges to mental health research and practice. Accumulating mental health research encourages a shift in focus towards transdiagnostic dimensional features that are shared across categorical disorders due to difficulties identifying causes, biomarkers, and treatments with specificity to individual disorders. In support of this shift, transdiagnostic research has identified a general psychopathology factor – often called the ‘p’ factor – that accounts for shared variation across internalizing, externalizing, and thought disorders in diverse samples. Identifying neural correlates of this general psychopathology factor would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the p factor may contribute to risk. Previous research by the applicant has identified relations between the p factor and structural alterations within a cerebello-thalamo-cortical circuit (CTCC), involved in higher-order cognitive and emotional processing. An F32 postdoctoral fellowship would allow the applicant to critically expand this research by examining replicability, mechanisms, and trajectory of associations between CTCC neural alterations and p factor scores in two large, openly available existing datasets: the Consortium for Neuropsychiatric Phenomics (CNP) and the Adolescent Brain and Cognitive Development (ABCD) studies. The CNP includes healthy adults and patients (aged 21-50) with attention deficit/hyperactivity disorder, bipolar disorder, and schizophrenia. ABCD includes a nationally representative sample of youth (aged 9-10) who are being followed longitudinally for 10 years. Using data from these two studies will allow the applicant to (1) examine whether the association between p factor scores and CTCC alterations are identifiable in youth, prior to the onset of most major mental illnesses (ABCD), and in patients with serious mental illness (CNP), (2) test neurocognitive mechanisms underlying this association, and (3) trace unfolding of symptoms over time related to these neural alterations. In addition, the applicant will conduct a feasibility study in healthy young adults to learn how to reliably activate the CTCC during a cognitive control task and provide pilot data for future grants. With substantial research and training opportunities available at McLean Hospital/Harvard Medical School, the mentorship of Dr. Diego Pizzagalli (primary mentor), a leader in the field of clinical neuroscience of depression, and the consultation of Dr. Roman Kotov (expert in statistical modeling of psychiatric symptoms) and Dr. Blaise Frederick (expert in magnetic resonance imaging physics), the applicant will receive training in all aspects of MRI experimental design and analysis, statistical modeling of the structure and trajectory of symptoms over time, professional development skills, and in designing and implementing her first independent functional MRI (fMRI) study. Together, the proposed training plan will support the applicant in contributing to transdiagnostic neuroscience research, honing skills in statistical modeling and advanced neuroimaging research, and building a program of independent research.