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

与一般精神病理学相关的神经改变的可重复性、机制和轨迹

基本信息

批准号：
10454130
负责人：
Adrienne Lynn Romer
金额：
$ 7.06万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10454130
关键词：
10 year old Accounting Adolescent Adult Affective Age Anisotropy Attention deficit hyperactivity disorder Back Biological Markers Bipolar Disorder Birth Brain Brain region Categories Cerebellum Clinical Cognitive Communities Consultations Data Data Collection Data Set Deformity Development Diagnostic Dimensions Disease Early identification Emotional Etiology Experimental Designs Feasibility Studies Fellowship Functional Magnetic Resonance Imaging Future Grant Hospitals Individual Intervention Joints Lead Learning Longitudinal Studies Magnetic Resonance Imaging Major Mental Illness Mediating Mental Depression Mental Health Mental disorders Mentors Mentorship Meta-Analysis Monitor Motor Nature Neurosciences Neurosciences Research Patients Pattern Physics Pontine structure Population Prefrontal Cortex Process Properdin Psychopathology Reporting Research Research Training Risk Role Sampling Schizophrenia Services Severities Severity of illness Short-Term Memory Specificity Statistical Models Structure Symptoms Testing Time Training Variant Work Youth aged base cognitive control cognitive development cognitive task cohort comorbidity complement C2a design executive function experimental analysis gray matter health practice healthy volunteer improved improved outcome information processing insight longitudinal dataset medical schools multimodal neuroimaging neural circuit neural correlate neurocognitive test neuroimaging neuropsychiatry novel phenomics preadolescence prevent programs psychiatric comorbidity psychiatric symptom relating to nervous system severe mental illness skill acquisition skills theories training opportunity young adult

项目摘要

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.

项目总结/摘要精神科合并症的高发病率（约50%的成年人）对心理健康研究构成了重大挑战，实践积累心理健康研究鼓励重点转向跨诊断维度由于难以识别病因、生物标志物和对个别疾病进行特异性治疗。为了支持这一转变，转诊断研究已经确定，一个一般的精神病理学因素-通常被称为'p'因素-解释了跨性别的共享差异。内化，外化，和思维障碍在不同的样本。识别这种普遍的神经相关性精神病理学因素将证实其在表征精神障碍的共同起源方面的重要性并帮助我们开始理解p因子可能导致风险的机制。先前申请人的研究已经确定了P因子和结构改变之间的关系，小脑-丘脑-皮层回路（CTCC），参与高级认知和情绪处理。一架F32 博士后奖学金将允许申请人通过检查可复制性来批判性地扩展这项研究，机制，以及CTCC神经改变和p因子评分之间的关联轨迹，公开可用的现有数据集：神经精神表型组学联盟（CNP）和青少年大脑和认知发展（ABCD）研究。CNP包括健康成人和患者（21 - 50岁）注意力缺陷多动障碍躁郁症和精神分裂症ABCD包括一个全国性的青年（9 - 10岁）的代表性样本，他们被纵向跟踪了10年。使用的数据来自这两项研究将允许申请人（1）检查p因子得分与 CTCC的改变在青年、大多数主要精神疾病（ABCD）发作之前和老年人中是可识别的。严重精神疾病（CNP）患者，（2）测试这种关联的神经认知机制，以及 (3)追踪与这些神经变化相关的症状随时间的演变。此外，申请人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，并为未来的赠款提供试点数据。提供大量研究和培训机会在McLean医院/哈佛医学院，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Blaise Frederick博士（磁共振成像物理学专家），申请人将接受MRI实验设计和分析，统计建模，随着时间的推移，症状的结构和轨迹，专业发展技能，以及在设计和进行她的第一个独立的功能性磁共振成像研究。拟议的培训计划将共同支持申请人在促进跨诊断神经科学研究，磨练统计建模技能，先进的神经影像学研究，并建立一个独立的研究计划。