Nutritional Components of Psychiatric Disease and Treatment Response

精神疾病的营养成分和治疗反应

• 批准号: 8242126
• 负责人: SIMON J EVANS
• 金额: $ 14.63万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-09 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242126
• 关键词: Accounting; Arachidonic Acids; Award; Basic Science; Biological Assay; Biological Markers; Biometry; Bipolar Disorder; Brain; Chronic; Clinic; Clinical; Clinical Research; Complex; Data; Diet; Diet and Nutrition; Dietary Component; Dietary Factors; Disease; Education; Equilibrium; Essential Fatty Acids; Ethics; Etiology; Fatty Acid Desaturases; Fatty acid glycerol esters; Genes; Genetic; Genetic Variation; Genotype; Human; Intake; Intervention Trial; Journals; Kinetics; Lipids; Literature; Measures; Mental Health; Mental disorders; Mentored Research Scientist Development Award; Mentors; Metabolic; Metabolism; Modeling; Molecular and Cellular Biology; Mood Disorders; Mood stabilizers; Moods; Neurobiology; Neurons; Nutrient; Nutritional; Omega-3 Fatty Acids; Omega-6 Fatty Acids; Pathway interactions; Patients; Pharmaceutical Preparations; Physiological; Play; Polyunsaturated Fatty Acids; Process; Property; Psychiatric therapeutic procedure; Psychiatrist; Recording of previous events; Relative (related person); Research; Research Personnel; Research Training; Resistance; Role; Science; Serum; Signal Transduction; Single Nucleotide Polymorphism; Staging; Supplementation; System; Technology; Testing; Tissues; Training; Translational Research; Variant; burden of illness; enzyme activity; gene interaction; genetic variant; improved; instrument; lipid metabolism; metabolomics; neurochemistry; nutrition; receptor; research study; response; success; treatment response

DESCRIPTION (provided by applicant): With the research and training proposed in this application, I will build on my formal education in molecular and cellular biology and research in the neurobiology of mood disorders, to develop rare expertise understanding dietary components of mental illness. There is ample basic science evidence that diet and nutrition influence brain function and psychiatric illness. However, psychiatrists rarely explore nutritional issues in the clinic due to the relative lack of systematic clinical research. I aim to use the K01 award to develop translational research expertise in the role of dietary factors at the interface between mood and metabolism. The training component of this application includes mentored training in metabolomic sciences, clinical research in bipolar disorder, genetics, and biostatistics; as well as didactic training in human nutrition science, biostatistics, and the ethics of human research. The research component of this application focuses on a specific hypothesis regarding the role of essential fatty acids in bipolar disorder and integrates all aspects of the mentored and didactic training. Previous research implicates polyunsaturated fatty acids (PUFA) in bipolar disorder. Low tissue concentrations of omega-3 fatty acids associate with bipolar disorder, and several studies show that supplementing omega-3s may be efficacious in treating the disease. However, the data are confounded because the tissue ratio of omega-3s to omega-6s is also important, since these two classes of PUFA compete with each other and play many opposing physiological roles. Their tissue concentrations largely reflect the diet, however, allelic variation in genes that regulate lipid metabolism are also involved. Therefore, there is a diet by gene interaction in the control of PUFA profiles. Interestingly, one proposed mechanism of action for mood stabilizer medications used to treat bipolar disorder is the specific inhibition of turnover and downstream signaling of the omega-6, arachidonic acid, in neurons. Previous studies evaluating the efficacy of omega-3s in treating bipolar disorder, and on-going use of mood stabilizers, have not taken dietary or genetic factors relative to omega-6 activity into account. Therefore, this represents a new avenue for clinical research. High omega-6 tissue levels, especially those of arachidonic acid, may oppose the efficacy of omega-3 supplementation or mood stabilizer treatment approaches, yet this has not been evaluated. With the proposed research, we will evaluate the contribution of diet and genetic variants controlling PUFA profiles, to bipolar disorder etiology and treatment resistance. With the current award, I will train in human nutrition, metabolomics and clinical psychiatric research and apply the training to test a hypothesis for the role of a specific diet by gene interaction in bipolar disorder. I will emerge from this training as a competitive clinical researcher in a field that has a significant potential to impact current psychiatric practice by understanding complex dietary factors that influence mental health and disease. PUBLIC HEALTH RELEVANCE: The role of dietary factors in psychiatric illness etiology and treatment is not well understood, despite a large basic science literature implicating nutrients in the control of neurochemical circuits and brain function. The current proposal aims develop expertise in human nutrition at the interface between mood and metabolism and conduct clinical research studies to understand dietary factors in mental health.

描述(由申请人提供)：通过本申请中建议的研究和培训，我将在我在分子和细胞生物学以及情绪障碍的神经生物学研究方面的正规教育的基础上，发展了解精神疾病的饮食成分的罕见专业知识。有充分的基础科学证据表明，饮食和营养会影响大脑功能和精神疾病。然而，由于相对缺乏系统的临床研究，精神病学家很少在临床上探索营养问题。我的目标是利用K01奖来发展饮食因素在情绪和新陈代谢之间的界面上所起作用的翻译研究专业知识。该应用程序的培训部分包括新陈代谢科学、双相情感障碍临床研究、遗传学和生物统计学方面的指导性培训，以及人类营养科学、生物统计学和人类研究伦理方面的授课培训。该应用程序的研究部分集中在关于必需脂肪酸在双相情感障碍中的作用的特定假设上，并整合了指导和说教培训的所有方面。以前的研究表明，多不饱和脂肪酸(PUFA)与躁郁症有关。组织中低浓度的omega-3脂肪酸与双相情感障碍有关，几项研究表明，补充omega-3脂肪酸可能对治疗这种疾病有效。然而，数据是混乱的，因为omega-3和omega-6的组织比例也很重要，因为这两类多不饱和脂肪酸相互竞争，发挥着许多相反的生理作用。它们的组织浓度在很大程度上反映了饮食，然而，调节脂肪代谢的基因的等位基因变异也参与其中。因此，在控制多不饱和脂肪酸含量的过程中，存在基因互作的饲料效应。有趣的是，情绪稳定剂药物用于治疗双相情感障碍的一个被提出的作用机制是特异性地抑制神经元中omega-6-花生四烯酸的周转和下游信号。之前评估omega-3对双相情感障碍疗效的研究，以及正在进行的情绪稳定剂的使用，都没有考虑与omega-6活性相关的饮食或遗传因素。因此，这代表了临床研究的一条新途径。高的omega-6组织水平，特别是花生四烯酸的水平，可能会阻碍omega-3补充或情绪稳定剂治疗方法的有效性，但这还没有得到评估。通过拟议的研究，我们将评估控制PUFA谱的饮食和遗传变异对双相情感障碍病因和治疗耐药性的贡献。有了目前的奖项，我将接受人类营养学、新陈代谢组学和临床精神病学研究方面的培训，并应用培训来测试特定饮食通过基因交互作用在双相情感障碍中所起作用的假设。我将从这次培训中脱颖而出，成为一名有竞争力的临床研究人员，该领域通过了解影响心理健康和疾病的复杂饮食因素，有很大潜力影响当前的精神病学实践。 与公共健康相关：饮食因素在精神疾病病因和治疗中的作用尚不清楚，尽管有大量基础科学文献表明营养物质控制神经化学回路和大脑功能。目前的建议旨在发展情绪和新陈代谢之间的人类营养方面的专业知识，并进行临床研究，以了解饮食因素对心理健康的影响。