Behavioral Approach System Dysregulation in Adolescents with Bipolar Disorder

双相情感障碍青少年的行为方法系统失调

• 批准号: 8240641
• 负责人: Snezana Urosevic
• 金额: $ 15.47万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8240641
• 关键词: Address; Adolescence; Adolescent; Adult; Age; Automobile Driving; Behavior; Behavioral; Biological; Biological Markers; Bipolar Disorder; Brain; Brain Mapping; Brain region; Child; Childhood; Clinical; Clinical Psychology; Cognitive; Collaborations; Comorbidity; Coupled; Data; Data Set; Decision Making; Development; Diagnosis; Disease; Doctor of Philosophy; Early treatment; Educational workshop; Electroencephalography; Equation; Event; Exhibits; Faculty; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Grant; Human; Hypersensitivity; Impairment; Incentives; Individual; International; Intervention; Interview; K-Series Research Career Programs; Lead; Learning; Life; Light; Link; Longevity; Measures; Mental disorders; Mentally Ill Persons; Mentors; Mentorship; Methods; Minor; Mission; Modeling; Motivation; Nature; Patient Self-Report; Patients; Personality Traits; Population; Positioning Attribute; Process; Publications; Punishment; Questionnaires; Recurrence; Research; Research Personnel; Rewards; Risk; Risk Factors; Secure; Severities; Signal Transduction; Societies; Specific qualifier value; Structure; Sum; Symptoms; System; Testing; Theoretical model; Training; Ventral Striatum; behavior measurement; career; career development; childhood bipolar disorder; cost; disability; experience; follow-up; indexing; information processing; insight; meetings; neurobehavioral; neuropsychological; outcome forecast; prospective; psychologic; psychosocial; relating to nervous system; response; reward processing; stem; suicide rate; symposium; tool; trait; years lived with disability

DESCRIPTION (provided by applicant): The proposed project focuses on a study of adolescents with bipolar spectrum disorders (i.e., bipolar I, bipolar II, or bipolar NOS disorder), a spectrum of debilitating mental illnesses that lead to widespread impairments in functioning. Given recent research that suggests that more than 60% of adults with bipolar disorders experience first onset of their illness prior to age 18, adolescents with bipolar disorders are an important population to investigate. The proposed project has three objectives: 1) characterizing abnormalities in responses to and processing of reward information, a proposed core dysfunction, in adolescents with bipolar disorders; 2) identifying most sensitive predictors of prospective bipolar episode course and bipolar symptoms in adolescence; and finally, 3) confirming that multiple indices of reward processing abnormalities are tapping into a single system given theoretical models that propose bipolar disorders' core dysregulation to be in behavioral approach system (BAS), a system functioning to respond to environmental rewards. In order to accomplish the first objective, the proposed project will examine reward sensitivity and reward information processing in adolescents with bipolar disorders and in healthy adolescents, using a set of behavioral tasks, self-report measures, and measures of reward-relevant brain activity as indexed by electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). In order to accomplish the second objective, the proposed project will assess prospective bipolar symptoms and episodes during a one-year follow-up and examine which indices of reward sensitivity (i.e., self-report, behavioral, EEG, or fMRI) are the most sensitive predictors of bipolar symptom severity. Finally, in order to accomplish the third objective, multi-method indices of reward sensitivity (i.e., self-report, behavioral, EEG, fMRI) will be analyzed using structural equation modeling to determine whether they tap into a single, latent construct. The proposed project has a potential to shed light on biological and psychological mechanisms driving bipolar symptoms in adolescence. It also has a potential to provide clinical tools for identifying risk factors for worsening course of bipolar disorders and identifying patients in urgent need of aggressive early intervention. Thus, the proposed project fits with the NIMH's larger mission to investigate causes of mental illness and to understand mental illness trajectories in order to treat mental illness effectively. Candidate's career goals and training plan. Dr. Snezana Urosevic's long-term career goal is to study behavioral activation/approach system (BAS) dysfunction in bipolar spectrum disorders, with specific emphasis on development of this BAS dysfunction across the life span. She aims to use multitude of psychosocial, behavioral, and neural indices of BAS functioning to understand the bipolar disorders' BAS dysregulation, a proposed core vulnerability in bipolar disorders. Dr. Urosevic aims to secure a tenure-track faculty position within the next 5 years, which would allow her to pursue these career research goals. In order to accomplish these long-term goals, Dr. Urosevic's immediate career development objectives are: 1) to gain expertise in research on adolescents with bipolar disorders, thus expanding her current research background with adult bipolar disorder populations; 2) to gain expertise in functional magnetic resonance imaging (fMRI), expanding the repertoire of methods for assessing neural correlates of BAS functioning in bipolar disorders; 3) to gain expertise in structural equation modeling, which would allow her to empirically assess relationship among various indices of BAS functioning in bipolar disorders; and 4) to develop into an independent investigator through increasing her publications record, obtaining a tenure-track faculty position, and applying for a R-01 grant. The proposed K-award will provide crucial mentorship and training, in order for Dr. Urosevic to meet these immediate career development goals. Her K-award training plan includes coursework in relevant topics (e.g., hands-on workshops on fMRI, structural equation modeling), attendance and presentations at appropriate international and national research meetings (e.g., Human Brain Mapping, International Conference on Bipolar Disorder), and extensive collaborations with her mentor, Monica Luciana, Ph.D., and co-mentors, Drs. Kathleen Thomas, Robert Krueger, Eric Youngstrom, and Jonathan Jensen. This mentoring team has a set of expertise that neatly fit with Dr. Urosevic's immediate career development goals. Dr. Luciana is an expert in adolescent neurobehavioral development in healthy and mentally ill populations, as well as in studying indices of BAS-relevant dopaminergic functioning. This is coupled with Dr. Younstrom's extensive experience in research on assessment and phenomenology of pediatric bipolar disorders and Dr. Jensen's clinical experience with assessment and treatment of pediatric bipolar disorders. In addition, Dr. Thomas has expertise in fMRI research on pediatric populations and in assessing reward processing in minors using fMRI, and Dr. Krueger has expertise in structural equation modeling in clinical psychology research. In summary, the proposed K-award promises to provide important scientific insights into adolescent bipolar disorders, as well as to launch the candidate's, Dr. Urosevic's, independent research career. PUBLIC HEALTH RELEVANCE: Bipolar disorder has been proposed to be the fifth leading cause of years lived with disability of all physical and mental illnesses in the world (WHO, 2001). According to a recent study, majority of adults with bipolar disorders experience first onset prior to age 18 (Beesdo et al., 2009), but very little is known about causes of bipolar illness in children and adolescence. The proposed project's focus on understanding brain and behavioral processes leading to bipolar symptoms in adolescence has a potential to inform future interventions and reduce both individual suffering and society's cost stemming from bipolar disorder disability.

描述（由申请人提供）：拟议的项目重点研究患有双相情感障碍的青少年（即双相情感障碍I，双相情感障碍II或双相情感障碍NOS），这是一种导致广泛功能障碍的衰弱性精神疾病。鉴于最近的研究表明，超过60%的双相情感障碍成人患者在18岁之前首次发病，青少年双相情感障碍患者是一个重要的调查人群。该项目有三个目标：1)描述双相情感障碍青少年对奖励信息的反应和处理异常，这是一种被提出的核心功能障碍；2)确定青春期双相情感障碍最敏感的预测因素；最后，3)确认奖励处理异常的多个指标正在进入一个单一的系统，给出的理论模型表明双相情感障碍的核心失调是在行为方法系统（BAS）中，这是一个对环境奖励做出反应的系统。为了实现第一个目标，拟议的项目将使用一套行为任务、自我报告测量和由脑电图（EEG）和功能磁共振成像（fMRI）索引的与奖励相关的大脑活动测量来检查双相情感障碍青少年和健康青少年的奖励敏感性和奖励信息处理。为了实现第二个目标，该计划将在一年的随访期间评估预期的双相症状和发作，并检查奖励敏感性指标（即自我报告、行为、脑电图或功能磁共振成像）是双相症状严重程度最敏感的预测因子。最后，为了实现第三个目标，将使用结构方程模型分析奖励敏感性的多方法指标（即自我报告、行为、脑电图、功能磁共振成像），以确定它们是否触及单一的潜在构念。拟议的项目有可能阐明驱动青少年双相症状的生物学和心理学机制。它也有可能为识别双相情感障碍恶化过程的危险因素和识别迫切需要积极早期干预的患者提供临床工具。因此，拟议的项目符合NIMH更大的使命，即调查精神疾病的原因，了解精神疾病的轨迹，以便有效地治疗精神疾病。候选人的职业目标和培训计划。Snezana Urosevic博士的长期职业目标是研究双相情感障碍的行为激活/接近系统（BAS）功能障碍，特别强调这种BAS功能障碍在整个生命周期中的发展。她的目标是利用BAS功能的大量社会心理、行为和神经指标来理解双相情感障碍的BAS失调，这是双相情感障碍的核心脆弱性。Urosevic博士的目标是在未来五年内获得终身教职，这将使她能够追求这些职业研究目标。为了实现这些长期目标，Dr. Urosevic的近期职业发展目标是：1)在青少年双相情感障碍的研究中获得专业知识，从而扩大她目前在成人双相情感障碍人群中的研究背景；2)获得功能性磁共振成像（fMRI）方面的专业知识，扩大评估双相情感障碍中BAS功能神经相关因素的方法；3)获得结构方程建模的专业知识，这将使她能够经验性地评估双相情感障碍中BAS功能各指标之间的关系；4)通过增加她的出版记录，获得终身教职，并申请R-01补助金，发展成为一名独立的研究者。拟议的k奖将提供重要的指导和培训，以使乌鲁塞维奇博士实现这些直接的职业发展目标。她的k奖培训计划包括相关主题的课程（例如，功能磁共振成像，结构方程建模的实践研讨会），出席适当的国际和国家研究会议并发表演讲（例如，人脑测绘，双相情感障碍国际会议），以及与她的导师Monica Luciana博士和共同导师Monica Luciana博士的广泛合作。凯瑟琳·托马斯，罗伯特·克鲁格，埃里克·扬斯特罗姆和乔纳森·詹森。这个指导团队有一套专业知识，正好符合乌鲁塞维奇博士的近期职业发展目标。Luciana博士是健康和精神疾病人群青少年神经行为发展方面的专家，也是研究bas相关多巴胺能功能指数的专家。这与Younstrom博士在儿童双相情感障碍评估和现象学研究方面的丰富经验以及Jensen博士在儿童双相情感障碍评估和治疗方面的临床经验相结合。此外，Thomas博士在儿科人群的fMRI研究和使用fMRI评估未成年人的奖励处理方面拥有专业知识，Krueger博士在临床心理学研究的结构方程建模方面拥有专业知识。总之，拟议中的k奖有望为青少年双相情感障碍提供重要的科学见解，并启动候选人乌鲁塞维奇博士的独立研究生涯。