Neural mechanisms underlying abnormal food reward processing in depressed women

描述(由申请人提供)：流行病学和行为学研究表明，严重抑郁障碍(MDD)和肥胖之间的共病在女性中尤其强烈，甚至可能仅限于女性，甚至控制了人口统计变量。此外，与体重正常的患者相比，患有MDD的肥胖患者表现出更差的治疗结果。考虑到与情绪调节和食物摄入的这些共病干扰相关的重大健康负担，更好地描述MDD和肥胖之间已确定但研究不足的关系是很重要的。这项有指导的研究科学家发展计划的目的是帮助应聘者实现以下目标：a)获得情绪障碍的临床症状学和精神治疗方面的经验；b)建立神经内分泌系统的知识库，这是情绪障碍和异常食物动机研究的组成部分；c)获得功能磁共振数据高级建模方面的专家培训；d)加强她对下丘脑离散核中关键激素和神经肽信号的理解；e)继续扩大她在精神障碍大脑性别差异领域的技能。在Jill Goldstein博士[BWH的大脑性别差异和激素在精神疾病中的作用的专家]、Anne Klibanski博士[MGH的神经内分泌学专家]、David SilberSweig博士(BWH的MDD神经精神病学专家)、Laura Miller博士(BWH的女性心理健康专家)和Susan Whitfield-Gabrieli博士(麻省理工学院的数学家，擅长先进的fMRI方法学)的大力指导下，应聘者将发展必要的技能，以便在情绪障碍和异常食物动机的研究中获得独立性，使用结合功能神经成像和神经内分泌技术的跨学科方法。这项研究计划的目标是：1)使用功能磁共振成像，描述患有MDD的肥胖女性与患有MDD的健康体重女性、没有MDD的健康体重女性以及没有MDD的肥胖女性在食物奖励相关区域的大脑激活模式的潜在差异；2)确定MDD女性皮质下感兴趣区的大脑激活与HPA/HPG轴激素和食欲调节肽之间的关系；以及3)测试MDD症状与a)HPA/HPG轴激素和食欲调节多肽之间的关系；以及b)在MDD和肥胖女性中，食物奖励回路功能。候选人的长期目标是与治疗专家合作，利用这些技术和从这些初步研究中获得的知识来设计预防、预测和治疗效果研究。BWH精神科和放射科、妇女健康部、MGH Martinos生物医学成像中心和哈佛临床和翻译科学中心提供的设施为应聘者提供了一个世界级的环境，在其中执行她的职业发展计划活动和拟议的研究。 与公共卫生相关：妇女患严重抑郁障碍和肥胖的风险更高，这两种疾病的共同出现与不良的治疗结果有关。该项目将通过检测抑郁症和肥胖症女性大脑中与食物奖励和调节情绪和食欲的激素相关的区域的异常，更好地描述抑郁症和肥胖症之间已被识别但研究不足的关系。了解导致女性抑郁和肥胖的共同大脑和激素途径将为开发针对性别的预防性治疗方法提供基础，并减轻与这种共病相关的疾病负担。

DESCRIPTION (provided by applicant): The comorbidity between major depressive disorder (MDD) and obesity appears especially strong in and perhaps limited to females, even controlling for demographic variables, as evidenced by epidemiological and behavioral studies. Further, obese patients with MDD demonstrate worse treatment outcomes compared to healthy-weight counterparts. Given the significant health burden associated with these comorbid disturbances of emotion regulation and food intake, it is important to better characterize the identified but understudied relationship between MDD and obesity. The purpose of this Mentored Research Scientist Development Plan is to assist the candidate in achieving the following goals: a) gain experience in clinical symptomatology and psychiatric treatment of mood disorders, b) develop a knowledge base in the neuroendocrine system, integral to the study of mood disorders and abnormal food motivation, c) obtain expert training in advanced modeling of fMRI data, d) enhance her understanding of critical hormone and neuropeptide signaling in discrete hypothalamic nuclei, all while e) continuing to expand her skills in the field of sex differences in the brain in psychiatric disorders. Under the strong mentorship of Dr. Jill Goldstein [an expert on sex differences in the brain and the role of hormones in psychiatric disorders at Brigham and Women's Hospital (BWH)], Dr. Anne Klibanski [an expert in neuroendocrinology at Massachusetts General Hospital (MGH)], Dr. David Silbersweig (an expert in neuropsychiatry in MDD at BWH), Dr. Laura Miller (an expert in women's mental health at BWH) and Dr. Susan Whitfield-Gabrieli (a mathematician at Massachusetts Institute of Technology with expertise in advanced fMRI methodology), the candidate will develop requisite skills to gain independence in the study of mood disturbances and abnormal food motivation using an interdisciplinary approach combining functional neuroimaging and neuroendocrine techniques. The research plan aims to 1) delineate, using fMRI, potential differences in brain activation patterns in regions implicated in food reward in obese women with MDD compared with healthy-weight women with MDD, healthy-weight women without MDD, and obese women without MDD; 2) identify relationships between brain activation in subcortical regions of interest and HPA- /HPG-axis hormones and appetite-regulatory peptides in women with MDD and obesity; and 3) test hypotheses regarding associations between MDD symptoms and a) HPA-/HPG-axis hormones and appetite-regulatory peptides, and b) food reward circuitry functioning, in women with MDD and obesity. The candidate's long term goal is to collaborate with treatment specialists to use these techniques and the knowledge gained from these initial studies to design prevention, prediction, and treatment efficacy studies. Facilities provided through the BWH Departments of Psychiatry and Radiology and Division of Women's Health, MGH Martinos Center for Biomedical Imaging, and Harvard Clinical and Translational Science Center, offer the candidate a world-class environment in which to execute her career development plan activities and proposed research. PUBLIC HEALTH RELEVANCE: Women are at a higher risk of developing major depressive disorder and obesity, the co-occurrence of which is associated with poor treatment outcomes. This project will better characterize the identified but understudied relationship between depression and obesity by examining abnormalities in brain regions related to food reward and hormones that regulate mood and appetite in women with depression and obesity. Understanding the shared brain and hormonal pathways that lead to depression and obesity in women will provide a basis for the development of sex-specific preventative approaches to treatment and ease the disease burden associated with this comorbid condition.