Neuromorphometry of Psychosis in Bipolar Disorder

双相情感障碍精神病的神经形态测量

• 批准号: 7991854
• 负责人: DANIEL MAMAH
• 金额: $ 17.12万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991854
• 关键词: 22q12; Affect; Anatomy; Anisotropy; Area; Basal Ganglia; Biological; Bipolar Disorder; Brain; Brain Mapping; Brain Pathology; Brain region; Characteristics; Classification; Clinical; Corpus Callosum; Databases; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Doctor of Philosophy; Dopamine Receptor; Education; Epidemiology; Etiology; Family; Functional disorder; Funding; Future; Genetic; Grant; Hallucinations; Hippocampus (Brain); Knowledge; MRI Scans; Maps; Measures; Memory impairment; Mentors; Methodology; Metric; Molecular Genetics; Neurobiology; Patients; Pharmaceutical Preparations; Positron-Emission Tomography; Postdoctoral Fellow; Predisposition; Principal Investigator; Psychiatric Diagnosis; Psychiatry; Psychopathology; Psychotic Disorders; Published Comment; Radiology Specialty; Reporting; Research; Research Ethics; Research Methodology; Residencies; Resolution; Risk; Running; Scanning; Schizophrenia; Severities; Shapes; Short-Term Memory; Structure; Susceptibility Gene; Syndrome; Thalamic structure; Training; United States National Institutes of Health; Universities; Washington; base; clinical practice; computational anatomy; disease classification; disorder subtype; endophenotype; experience; gray matter; imaging modality; improved; interest; medical schools; neuroimaging; programs; public health relevance; tool; white matter

DESCRIPTION (provided by applicant): Although current nosology defines schizophrenia (SCZ) and bipolar disorder as unique constructs with distinctive clinical characteristics, there exist significant symptomatic and familial overlap. Epidemiologic and genetic studies suggest that SCZ shares common susceptibility genes with psychotic bipolar disorder (PBD), as opposed to nonpsychotic bipolar disorder (NPBD), suggesting that they may also share similar structural abnormalities in gray and white matter in the brain. We hypothesize that: 1) PBD and NPBD will differ in measures of subcortical gray matter and white matter integrity, 2) abnormalities in PBD will be intermediate between SCZ and NPBD, and 3) there will be a significant relationship between lifetime psychosis severity and structural measures. The Aims of this proposal are to: 1) collect MRI scans from 40 PBD and 40 NPBD subjects and generate volume and shape metrics for the hippocampus, thalamus and basal ganglia, and measures of corpus callosum integrity, 2) compare these measures between PBD, NPBD, SCZ and controls, and 3) correlate lifetime psychopathology with structural abnormalities in PBD and SCZ. This 5-year program will involve training in specific neuroimaging methodologies and the neurobiology of bipolar disorder, as well as general research and ethics. Imaging methods used in this proposal will be Large-Deformation High-Dimensional Brain Mapping and Diffusion Tensor Imaging. Deanna Barch, Ph.D. (Dept. of Psychiatry, Washington University), John Csernansky, MD (Northwestern University), Joshua Shimony, MD, PhD and Abraham Snyder, PhD, MD (both at the Dept. of Radiology, Washington University) will co-mentor the principal investigator's scientific development. All co-mentors have substantial experience in various areas of neuroimaging and in the application of related research methods, as well as experience training postdoctoral fellows and NIH grant recipients. The proposal is also supported by a rich diversity of collaborators and consultants to provide education and guidance in various aspects of research. The principal investigator has completed residency training in Psychiatry and a Masters in Psychiatric Epidemiology (MPE) at Washington University School of Medicine in St. Louis. PUBLIC HEALTH RELEVANCE: In clinical practice, treatments used in schizophrenia and bipolar disorder often overlap, and selected medications are not effective in all those affected by these disorders. Identification of specific structural brain abnormalities that cross traditional diagnostic boundaries, as is proposed, would allow for the development of more specific treatments for those affected, and identify those at risk. Specific biological abnormalities will also help validate psychiatric diagnoses and improve the classification of disorders.

描述（由申请人提供）：虽然当前的疾病分类学将精神分裂症（SCZ）和双相情感障碍定义为具有独特临床特征的独特结构，但存在显着的症状和家族重叠。流行病学和遗传学研究表明，与非精神病性双相情感障碍 (NPBD) 不同，SCZ 与精神病性双相情感障碍 (PBD) 具有共同的易感基因，这表明它们在大脑灰质和白质中也可能具有相似的结构异常。我们假设：1) PBD 和 NPBD 在皮层下灰质和白质完整性的测量上有所不同，2) PBD 异常将介于 SCZ 和 NPBD 之间，3) 终生精神病严重程度和结构测量之间存在显着关系。该提案的目的是：1) 收集 40 名 PBD 和 40 名 NPBD 受试者的 MRI 扫描，生成海马体、丘脑和基底神经节的体积和形状指标，以及胼胝体完整性的测量值，2) 比较 PBD、NPBD、SCZ 和对照组之间的这些测量值，以及 3) 将终生精神病理学与 PBD 和 NPBD 的结构异常相关联。 SCZ。 这个为期 5 年的项目将涉及特定神经影像学方法和双相情感障碍神经生物学以及一般研究和伦理学的培训。该提案中使用的成像方法将是大变形高维脑成像和扩散张量成像。迪安娜·巴奇博士（华盛顿大学精神病学系）、John Csernansky 医学博士（西北大学）、Joshua Shimony 医学博士、博士和 Abraham Snyder 博士、医学博士（均来自华盛顿大学放射学系）将共同指导首席研究员的科学发展。所有共同导师在神经影像学的各个领域和相关研究方法的应用方面都拥有丰富的经验，以及培训博士后研究员和 NIH 资助获得者的经验。该提案还得到了丰富多样的合作者和顾问的支持，为研究的各个方面提供教育和指导。 主要研究者已在圣路易斯华盛顿大学医学院完成精神病学住院医师培训并获得精神病流行病学 (MPE) 硕士学位。 公共卫生相关性：在临床实践中，用于精神分裂症和双相情感障碍的治疗经常重叠，并且所选药物并非对所有受这些疾病影响的患者都有效。正如所提出的那样，识别跨越传统诊断界限的特定结构性大脑异常，将有助于为受影响的人开发更具体的治疗方法，并识别处于危险中的人。特定的生物学异常也将有助于验证精神病学诊断并改进疾病的分类。