Neuromorphometry of Psychosis in Bipolar Disorder

描述(由申请人提供)：尽管目前的病因学将精神分裂症(SCZ)和双相情感障碍定义为具有独特临床特征的独特概念，但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)具有共同的易感基因，而不是非精神病性双相情感障碍(NPBD)，这表明它们可能也具有类似的大脑灰质和白质结构异常。我们假设：1)PBD和NPBD在皮质下灰质和白质完整性的测量上将有所不同，2)PBD的异常将介于SCZ和NPBD之间，3)终生精神病的严重程度与结构性措施之间将存在显著的关系。这项建议的目的是：1)收集40名PBD和40名NPBD受试者的MRI扫描，生成海马体、丘脑和基底节的体积和形状指标，以及穹隆体部完整性的指标；2)比较PBD、NPBD、SCZ和对照组之间的这些指标；3)将终生精神病理与PBD和SCZ的结构异常联系起来。这项为期5年的计划将涉及特定神经成像方法和双相情感障碍的神经生物学方面的培训，以及一般研究和伦理学。这项提议中使用的成像方法将是大变形高维脑图和扩散张量成像。迪安娜·巴奇博士(系华盛顿大学精神病学博士)、John Csernansky医学博士(西北大学)、Joshua Shimony医学博士和Abraham Snyder博士(医学博士)。华盛顿大学放射学教授)将共同指导首席研究员的科学发展。所有合作导师都在神经成像的各个领域和相关研究方法的应用方面拥有丰富的经验，以及培训博士后研究员和NIH补助金获得者的经验。该建议还得到了丰富多样的合作者和顾问的支持，以便在研究的各个方面提供教育和指导。这位首席研究员已经完成了精神病学的住院医师培训，并在圣路易斯的华盛顿大学医学院获得了精神流行病学硕士学位。

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.