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: 8410082
• 负责人: SIMON J EVANS
• 金额: $ 14.71万
• 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/8410082
• 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.

描述（由申请人提供）：通过本申请中提出的研究和培训，我将在分子和细胞生物学方面的正规教育以及情绪障碍神经生物学研究的基础上，发展了解精神疾病饮食成分的罕见专业知识。有充足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，精神科医生很少在临床上探讨营养问题。我的目标是利用 K01 奖来发展关于饮食因素在情绪和新陈代谢之间的作用的转化研究专业知识。该应用程序的培训部分包括代谢组学科学、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教学培训。该应用程序的研究部分侧重于关于必需脂肪酸在双相情感障碍中的作用的特定假设，并整合了指导和教学培训的各个方面。先前的研究表明多不饱和脂肪酸（PUFA）与双相情感障碍有关。组织中 omega-3 脂肪酸浓度低与双相情感障碍有关，多项研究表明补充 omega-3 可能有效治疗该疾病。然而，这些数据令人困惑，因为 omega-3 与 omega-6 的组织比例也很重要，因为这两类 PUFA 相互竞争并发挥许多相反的生理作用。它们的组织浓度很大程度上反映了饮食，然而，调节脂质代谢的基因的等位基因变异也参与其中。因此，饮食中存在通过基因相互作用来控制PUFA谱的情况。有趣的是，用于治疗双相情感障碍的情绪稳定剂药物的一种拟议作用机制是特异性抑制神经元中 omega-6（花生四烯酸）的周转和下游信号传导。之前的研究评估了 omega-3 治疗双相情感障碍的功效，以及持续使用情绪稳定剂，但并未考虑与 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新途径。高 omega-6 组织水平，尤其是花生四烯酸，可能会对抗 omega-3 补充剂或情绪稳定剂治疗方法的功效，但这尚未得到评估。通过拟议的研究，我们将评估饮食和控制 PUFA 谱的遗传变异对双相情感障碍病因和治疗抵抗的贡献。凭借当前的奖项，我将接受人类营养、代谢组学和临床精神病学研究方面的培训，并应用培训来检验特定饮食通过基因相互作用在双相情感障碍中的作用的假设。通过这次培训，我将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，具有影响当前精神病学实践的巨大潜力。