The Neural Bases of Pathological Food Perception and Choice in Major Depression

描述（由申请人提供）：在这份导师研究科学家发展奖（K 01）的申请中，凯尔西蒙斯博士要求获得必要的培训，以使自己成为一名独立的神经科学家，研究抑郁症中的异常进食行为。与抑郁症相关的进食变化，可以表现为食欲和体重的增加或减少，这是很重要的，因为它们可能会产生严重的身体疾病，如肥胖及其伴随的身体疾病的风险，也可能阐明重度抑郁症（MDD）的不同病理生理学。实现这一长期目标需要西蒙斯博士发展跨学科的技能，包括抑郁症的临床神经科学，食物动机的神经科学和功能性神经成像。根据他以前的研究记录，西蒙斯博士在功能性神经成像方面表现出了专业知识。然而，为了完全实现他的目标，他需要与抑郁症神经生物学和食物动机专家一起工作的培训和经验。为此，西蒙斯博士将接受韦恩Drevets博士在抑郁症的神经生物学方面的指导，他是NIMH校内研究项目中情绪和焦虑障碍神经成像科的前科长，现任脑研究桂冠研究所（LIBR）主任。为了接受食物动机的神经生物学培训，西蒙斯博士将与卡里萨维奇博士密切合作，他是一位受人尊敬的食物动机功能神经成像研究者。拟议的培训计划还提供了获得高级统计建模和喂养神经生物学指导的机会，包括饥饿和饱腹感的代谢信号。培训和相关研究将在LIBR进行，LIBR是一个致力于进行神经成像和遗传学研究的最先进的研究所，旨在开发更有效的神经精神疾病治疗方法。LIBR与桂冠精神病学中心有着密切的联系。 诊所和医院，为可用于研究的临床人群，特别是患有情绪障碍的患者提供特殊的机会。通过他的导师提供的培训，以及LIBR的机构资源，西蒙斯博士将能够实现本提案的研究目标，即具体确定哪些大脑区域是MDD特征的喂养行为变化的基础，以及许多MDD患者之间喂养行为的显著差异。具体而言，拟议的研究将确定MDD是否与食物感知和食物相关决策过程中OFC，vmPFC或纹状体-苍白球神经回路内的异常活动相关（具体目标1），在食物感知和食物相关决策过程中，吞噬过多和吞噬不足的MDD亚型是否与不同的OFC、vmPFC或纹状体-苍白球神经回路反应相关（具体目标2），以及先前验证的快感缺失行为评级是否与MDD患者在食物感知和食物相关决策过程中的OFC、vmPFC或纹状体-苍白球神经回路反应相关（具体目标3）。

DESCRIPTION (provided by applicant): In this application for a Mentored Research Scientist Development Award (K01), Dr. Kyle Simmons requests support to acquire the training necessary to establish himself as an independent neuroscientist studying aberrant feeding behaviors in depression. Depression-related changes in feeding, which can be manifested either as increases or decreases in appetite and weight, are important because they may both engender risk for serious physical illnesses such as obesity and its concomitant physical illnesses, and may also elucidate the differential pathophysiologies of Major Depressive Disorder (MDD). Accomplishing this long-term goal requires that Dr. Simmons develop skills that cut across disciplines, including the clinical neuroscience of depression, the neuroscience of food motivation, and functional neuroimaging. Based on his prior research track record, Dr. Simmons has demonstrated expertise in functional neuroimaging. In order to fully attain his goals, however, he needs the training and experience that comes from working with experts in the neurobiology of depression, and food motivation. To that end, Dr. Simmons will receive mentoring in the neurobiology of depression from Dr. Wayne Drevets, the former Chief of the Section on Neuroimaging in Mood and Anxiety Disorders in the NIMH Intramural Research Program, and now Director of the Laureate Institute for Brain Research (LIBR). To receive training in the neurobiology of food motivation, Dr. Simmons will work closely with Dr. Cary Savage, a respected investigator in the functional neuroimaging of food motivation. The proposed training plan also provides opportunities to acquire instruction in advanced statistical modeling, and in the neurobiology of feeding, including metabolic signaling of hunger and satiety. The training, and associated research, will take place at LIBR, a state-of-the-art institue dedicated to conducting neuroimaging and genetics research aimed developing more effective treatments for neuropsychiatric disorders. LIBR is closely affiliated with the Laureate Psychiatric Clinic and Hospital, which provides exceptional access to clinical populations available for research, particularly patients with mood disorders. With the training offered by his mentors, and institutional resources at LIBR, Dr. Simmons will be able to achieve the research objectives of this proposal, namely to determine specifically which brain regions underlie the changes in feeding behavior that characterize MDD, and the marked differences in feeding behaviors that differentiate among many MDD patients. Specifically, the proposed research will identify whether MDD is associated with aberrant activity within the OFC, vmPFC, or striatal-pallidal neurocircuit during food perception and food-related decision making (Specific Aim 1), whether hyperphagic and hypophagic MDD subtypes are associated with distinct OFC, vmPFC, or striatal-pallidal neurocircuit responses during food perception and food-related decision making (Specific Aim 2), and whether previously validated behavioral ratings of anhedonia are related to MDD patients' OFC, vmPFC, or striatal-pallidal neurocircuit responses during food perception and food-related decision making (Specific Aim 3).