BIOMARKERS OF WEIGHT CHANGE IN ANOREXIA NERVOSA

 描述(由申请人提供)：我是北卡罗来纳大学精神病学系进食障碍卓越中心的助理教授。我接受过行为遗传学和饮食失调方面的培训，重点是神经性贪食症(BN)和相关症状学。我正在寻求“组学”(即基因组学、转录组学)、高级遗传流行病学方法、与神经性厌食症相关的精神病理学和纵向数据分析方面的培训。职业目标：我想通过将我对遗传学的特殊兴趣与我对神经性厌食症(ANN)治疗结果(特别是复发)的新兴兴趣结合起来，将饮食障碍后果的研究带到一个新的水平。因此，我的核心职业目标是发展对治疗结果的生物标记物(基因组标记物，生物标记物)的理解。我将利用这些知识来开发复发风险的综合概况，这将为新颖、生物信息和有效的治疗干预提供参考职业发展：我计划在五个领域建立我的技能和专长：1.精神病理学、治疗方法和结果；3.饮食失调领域的康复定义；3.高级经济学和遗传流行病学方法4.纵向数据分析，包括潜在的轨迹建模。5.负责任的研究行为。研究项目：拟议的项目利用现有资源，在北卡罗来纳大学使用两个正在进行的纵向父母项目，以确定住院治疗AN后复发的生物标记物。家长项目包括：1)神经性厌食症的生物标志物(BAN)--100名住院治疗的妇女在入院和出院时进行评估，然后在出院后3个月、7个月和12个月进行评估。评估包括生物标记物(皮质醇、促肾上腺皮质激素、去甲肾上腺素和基因表达)以及心理、行为和认知症状学；以及2)饮食障碍恢复之路(RRED)，BAN参与者(n=60)出院后1年和2年的随访。本提案中使用的复发定义为“体重变化”，即自出院以来体重减少(或增加并维持)的量(随访体重减去出院体重)。首先，我将使用RNAseq检测治疗体重恢复过程中基因表达的变化。其次，我将研究生物标记物(基因表达变化和HPA轴和肾上腺素能通路激活)与心理、行为和认知因素之间的关系，以及在专科饮食障碍住院病房(BAN样本)出院一年内的三个时间点的体重变化。这些结果将确定体重变化的初步情况。第三，使用在本授奖过程中学到的复杂的纵向建模策略，我将描述从住院患者出院到出院后2年的体重维持/复发的长期模式(RRED样本)。在未来的独立应用(R01)中，这些结果将有助于进一步探索经济学因素对治疗结果的影响--例如多基因风险评分的发展以及该评分对复发的影响，并为治疗和筛查提供生物靶点。只有通过了解治疗恢复的体重减轻的生物标志物，我们才能充分识别那些有复发风险的人，以便制定有效的治疗方案-最终改善结果。环境：研究和培训将在北卡罗来纳大学的精神病学和遗传学系进行。指导：指导团队包括首席导师、临床心理学家辛西娅·布利克博士，他是国际公认的进食障碍研究专家，其资助的兴趣范围从基因组学到治疗。二级导师包括：精神病学家、“精神病学组学”领域的顶尖专家帕特里克·沙利文博士；遗传流行病学家卡里·诺斯博士，他将提供纵向数据分析和方法方面的专业知识，并将遗传和非遗传数据整合到这些分析中；临床心理学家、进食障碍康复方面公认的专家安娜·巴多-科恩博士；以及定量心理学家和纵向建模专家丹尼尔·鲍尔博士。

 DESCRIPTION (provided by applicant): I am an Assistant Professor with the Center of Excellence for Eating Disorders in the Department of Psychiatry at The University of North Carolina (UNC). I have training in behavior genetics and eating disorders, with a focus on bulimia nervosa (BN) and related symptomatology. I am seeking training in "-omic sciences" (i.e., genomics, transcriptomics), advanced genetic epidemiological methods, anorexia nervosa- related psychopathology, and longitudinal data analysis. Career Goals: I want to bring eating disorder outcome research to the next level by merging my specific interest in genetics with my emerging interest in anorexia nervosa (AN) treatment outcome, specifically relapse. Thus, my core career goal is to develop an understanding of biomarkers (-omic markers, biological markers) of AN treatment outcome. I will use this knowledge to develop integrated profiles of relapse risk, which will inform novel, biologically-informed, and effective treatment interventions Career Development: I plan to build my skills and expertise in five areas: 1. AN psychopathology, treatment approaches, and outcome; 3. Definitions of recovery in the eating disorders field; 3. Advanced -omic sciences and genetic epidemiological methods 4. Longitudinal data analyses including latent trajectory modeling. 5. The responsible conduct of research. Research Project: The proposed project leverages existing resources by using two ongoing longitudinal parent projects at UNC to identify biomarkers of relapse after inpatient treatment for AN. Parent projects include: 1) Biomarkers of Anorexia Nervosa (BAN)-100 women admitted for inpatient treatment for AN assessed at admission and discharge, and then 3, 7, and 12 months post-discharge. Assessments include biomarkers (cortisol, adrenocorticotropic hormone, norepinephrine, and gene expression) as well as psychological, behavioral, and cognitive symptomatology; and 2) Road to Recovery in Eating Disorders (RRED), a subsample of BAN participants (n=60) followed-up 1 and 2-years post-discharge. The definition of relapse used in this proposal is operationalized as "weight change," or the amount of weight lost (or gained and maintained) since hospital discharge (follow-up weight minus discharge weight). First, I will examine gene expression change during therapeutic weight restoration using RNAseq. Second, I will examine the association between biomarkers (gene expression change and HPA-axis and adrenergic pathway activation) and psychological, behavioral, and cognitive factors and weight change at 3-time points within 1-year of discharge from treatment from a specialized eating disorder inpatient unit (BAN sample). These results will identify preliminary profiles of weight change. Third, using sophisticated longitudinal modeling strategies learned during the course of this award period, I will characterize the long-term pattern of weight maintenance/relapse from inpatient discharge to 2-years post-discharge in patients with AN (RRED sample). In future independent applications (R01s) these results will inform further exploration of the influence of -omic factors on treatment outcome-such as the development of a polygenic risk score and the impact of this score on relapse and provide biological targets for treatment and screening. Only through the understanding of biomarkers of theraputically restored weight loss in AN, can we fully identify those at risk for relapse in orderto develop effective treatment protocols-ultimately improving AN outcome. Environment: The research and training will take place in the Departments of Psychiatry and Genetics at UNC. Mentorship: The mentorship team includes lead mentor, Dr. Cynthia Bulik, a clinical psychologist, and internationally recognized expert in eating disorder research and whose funded interests range from genomics to treatment. Secondary mentors include: Dr. Patrick Sullivan, a psychiatrist and leading expert in "psychiatric -omics;" Dr. Kari North, a genetic epidemiologist who will provide expertise in longitudinal data analysis and methods and integrating genetic and nongenetic data into these analysis; Dr. Anna Bardone-Cone, a clinical psychologist and recognized expert in defining recovery in eating disorders; and Dr. Daniel Bauer, a quantitative psychologist and expert in longitudinal modeling.