Neural mechanisms underlying abnormal food reward processing in depressed women

抑郁女性食物奖励处理异常的神经机制

基本信息

批准号：
8657410
负责人：
LAURA McGrath HOLSEN
金额：
$ 17.36万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8657410
关键词：
Address Adrenal Glands Amygdaloid structure Anhedonia Anterior Appetite Regulation Behavior Behavioral Body Weight decreased Brain Brain region Cardiovascular Diseases Cell Nucleus Center for Translational Science Activities Chronic Clinical Clinical Sciences Comorbidity Data Depressed mood Desire for food Development Development Plans Eating Endocrine Environment Epidemiology Estradiol Fasting Female Food Food Energy Food Processing Functional Magnetic Resonance Imaging Functional disorder General Hospitals Goals Gonadal Hormones Health Hippocampus (Brain)Hormonal Hormones Hospital Departments Hospitals Hydrocortisone Hypothalamic structure Incidence Individual Institutes Insula of Reil Intake Knowledge Lead Leptin Literature Major Depressive Disorder Massachusetts Medial Medical Mental Depression Mental Health Mental disorders Mentors Mentorship Methodology Minority Modeling Mood Disorders Moods Motivation Nature Neuroendocrinology Neuropeptides Neurosecretory Systems Nucleus Accumbens Obesity Outcome Pathway interactions Patients Pattern Peptides Pituitary Gland Play Prefrontal Cortex Prevention Psychiatric therapeutic procedure Psychiatry Radiology Specialty Research Rewards Role Scientist Sex Characteristics Sexual Development Signal Transduction Specialist Stimulus Stress Structure Symptoms Techniques Technology Testing Training Treatment Efficacy Treatment outcome Weight Weight Gain Woman Women&apos s Health base bioimaging blood oxygen level dependent burden of illness career development cingulate gyrus design disability disturbance in affect emotion regulation energy balance experience ghrelin high risk hypothalamic pituitary gonadal axis insight interdisciplinary approach interest knowledge base mood regulation neurobiological mechanism neuroimaging neuromechanism neuropsychiatry novel relating to nervous system response reward circuitry reward processing sex skills stem

项目摘要

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.

描述（由申请人提供）：流行病学和行为研究证明，即使在控制人口变量的情况下，重度抑郁症（MDD）和肥胖之间的共病似乎在女性中尤其强烈，并且可能仅限于女性。此外，与健康体重的患者相比，患有重度抑郁症的肥胖患者的治疗结果更差。考虑到与情绪调节和食物摄入的这些共病障碍相关的重大健康负担，更好地描述 MDD 和肥胖之间已确定但尚未充分研究的关系非常重要。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症状学和精神治疗经验，b）开发神经内分泌系统的知识库，这是研究的一部分情绪障碍和异常食物动机，c) 获得功能磁共振成像数据高级建模方面的专家培训，d) 增强她对离散下丘脑核中关键激素和神经肽信号传导的理解，同时 e) 继续扩展她的技能在精神疾病中大脑的性别差异领域。在 Jill Goldstein 博士（布莱根妇女医院 (BWH) 大脑性别差异和激素在精神疾病中的作用方面的专家）和 Anne Klibanski 博士（马萨诸塞州总医院神经内分泌学专家）的大力指导下， MGH）]、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） BWH）和苏珊·惠特菲尔德-加布里埃利（Susan Whitfield-Gabrieli）博士（麻省理工学院的数学家，拥有先进的功能磁共振成像方法方面的专业知识），候选人将使用结合功能性的跨学科方法，培养必要的技能，以在情绪障碍和异常食物动机的研究中获得独立性。神经影像学和神经内分泌技术。该研究计划旨在 1) 使用功能磁共振成像技术，描绘患有 MDD 的肥胖女性与患有 MDD 的健康体重女性、不患有 MDD 的健康体重女性以及不患有 MDD 的肥胖女性相比，与食物奖励有关的区域大脑激活模式的潜在差异; 2) 确定患有 MDD 和肥胖症的女性皮质下感兴趣区域的大脑激活与 HPA-/HPG-轴激素和食欲调节肽之间的关系； 3) 在患有 MDD 和肥胖的女性中，测试有关 MDD 症状与 a) HPA-/HPG-轴激素和食欲调节肽，以及 b) 食物奖赏回路功能之间关联的假设。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 精神病学和放射学系以及妇女健康科、MGH 马蒂诺斯生物医学成像中心以及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来执行其职业发展计划活动，并提出了建议研究。