Neuromorphometry of Psychosis in Bipolar Disorder

描述（由申请人提供）：尽管目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不同临床特征的独特结构，但它们存在显著的症状和家族重叠。流行病学和遗传学研究表明，SCZ与精神病性双相情感障碍（PBD）有共同的易感基因，而非精神病性双相情感障碍（NPBD），这表明它们也可能在大脑灰质和白质中有相似的结构异常。我们假设：1)PBD和NPBD在皮质下灰质和白质完整性的测量上存在差异；2)PBD的异常将介于SCZ和NPBD之间；3)终生精神病严重程度与结构测量之间存在显著关系。本提案的目的是：1)收集40名PBD和40名NPBD受试者的MRI扫描，生成海马、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，2)比较PBD、NPBD、SCZ和对照组之间的这些测量，以及3)将PBD和SCZ的终生精神病理与结构异常联系起来。这个为期5年的项目将包括特定的神经成像方法和双相情感障碍的神经生物学，以及一般研究和伦理方面的培训。本研究采用的成像方法为大变形高维脑成像和弥散张量成像。Deanna Barch博士（华盛顿大学精神病学系）、John Csernansky医学博士（西北大学）、Joshua Shimony医学博士和Abraham Snyder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有丰富的经验，并有培养博士后和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，他们在研究的各个方面提供教育和指导。首席研究员在圣路易斯华盛顿大学医学院完成了精神病学住院医师培训和精神病学流行病学硕士学位（MPE）。

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.