Neural mechanisms underlying abnormal food reward processing in depressed women

描述（由申请人提供）：流行病学和行为研究证明，即使控制了人口统计学变量，重性抑郁症（MDD）和肥胖之间的共病在女性中似乎特别强，可能仅限于女性。此外，与健康体重的对应者相比，患有MDD的肥胖患者表现出更差的治疗结果。考虑到与这些情绪调节和食物摄入共病障碍相关的显著健康负担，更好地描述MDD和肥胖之间已确定但研究不足的关系非常重要。本指导研究科学家发展计划的目的是帮助候选人实现以下目标：a）获得情绪障碍的临床病理学和精神病学治疗经验，B）发展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）获得功能磁共振成像数据高级建模的专家培训，d）增强她对下丘脑离散核团中关键激素和神经肽信号传导的理解，同时e）继续扩展她在精神疾病大脑性别差异领域的技能。在Jill Goldstein博士（布里格姆妇女医院（BWH）大脑性别差异和激素在精神疾病中的作用专家）、Anne Klibanski博士（马萨诸塞州总医院（MGH）神经内分泌学专家）、大卫西尔伯斯维格博士（Silbersweig）的大力指导下，（BWH MDD神经精神病学专家），劳拉米勒博士（BWH的女性心理健康专家）和苏珊·惠特菲尔德-加布里埃利博士（马萨诸塞州理工学院的数学家，擅长先进的功能磁共振成像方法），候选人将发展必要的技能，以获得独立的情绪障碍和异常的食物动机的研究使用跨学科的结合功能性神经影像学和神经内分泌技术的方法。该研究计划的目的是：1）使用功能磁共振成像技术，描述患有MDD的肥胖女性与患有MDD的健康体重女性、没有MDD的健康体重女性和没有MDD的肥胖女性相比，在涉及食物奖励的区域中大脑激活模式的潜在差异; 2）确定感兴趣的皮层下区域的脑激活与HPA- /HPG-轴激素和食欲之间的关系，在患有MDD和肥胖症的女性中，测试关于MDD症状与a）HPA-/HPG-轴激素和食欲调节肽，和B）食物奖励回路功能之间的关联的假设。候选人的长期目标是与治疗专家合作，使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。通过BWH精神病学和放射学部门以及妇女健康部门，MGH Martinos生物医学成像中心和哈佛临床和转化科学中心提供的设施，为候选人提供了一个世界一流的环境，以执行她的职业发展计划活动和拟议的研究。

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.