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独特临床特征的独特结构，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，与非精神病性双相情感障碍（NPBD）相比，SCZ与精神病性双相情感障碍（PBD）具有共同的易感基因，这表明它们也可能在大脑中的灰质和白色物质中具有相似的结构异常。我们假设：1）PBD和NPBD在皮质下灰质和白色物质完整性的测量方面不同，2）PBD的异常介于SCZ和NPBD之间，3）终身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，并生成海马、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值，2）比较PBD、NPBD、SCZ和对照组之间的这些测量值，以及3）将终身精神病理学与PBD和SCZ中的结构异常相关联。 这个为期5年的计划将涉及具体的神经影像学方法和双相情感障碍的神经生物学，以及一般的研究和道德的培训。本提案中使用的成像方法将是大变形高维脑标测和扩散张量成像。Deanna Barch博士（部门）精神病学，华盛顿大学），约翰Csernansky，医学博士（西北大学），约书亚Shimony，医学博士，博士和亚伯拉罕斯奈德，博士，医学博士（都在部门。放射学，华盛顿大学）将共同指导主要研究者的科学发展。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，以及培训博士后研究员和NIH补助金获得者的经验。该提案还得到了各种各样的合作者和顾问的支持，在研究的各个方面提供教育和指导。 主要研究者在圣路易斯的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（MPE）硕士学位。 公共卫生相关性：在临床实践中，精神分裂症和双相情感障碍的治疗方法经常重叠，并且所选择的药物并不是对所有受这些疾病影响的人都有效。如所提议的，识别跨越传统诊断界限的特定结构性脑异常将允许为受影响的患者开发更具体的治疗方法，并识别那些处于风险中的患者。特定的生物异常也将有助于验证精神病诊断和改善疾病的分类。

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.