4/6 Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP)

4/6 精神病和情感研究领域和中间表型 (PARDIP)

• 批准号: 8506547
• 负责人: MATCHERI S. KESHAVAN
• 金额: $ 26.1万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8506547
• 关键词: Affective; Anatomy; Anxiety; Auditory; Biological; Biological Markers; Biology; Biomedical Research; Bipolar Disorder; Brain; Categories; Circadian Rhythms; Classification; Clinical; Cluster Analysis; Cognition; Cognition Disorders; Cognitive; Collaborations; Collection; Data; Data Set; Development; Diagnosis; Diagnostic; Dimensions; Discrimination; Disease; Emotional; Environmental Risk Factor; Equipment; Etiology; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genetic; Genotype; Goals; Gray unit of radiation dose; Hamilton Rating Scale for Depression; Heterogeneity; Impairment; Impulsivity; Individual; Joints; Laboratories; Literature; Magnetic Resonance Imaging; Manic; Measures; Mental disorders; Methods; Moods; Neuroanatomy; Neurobiology; Neurocognitive; Patients; Pattern; Persons; Phenotype; Procedures; Process; Psychiatry; Psychopathology; Psychotic Disorders; Recording of previous events; Recruitment Activity; Research; Research Infrastructure; Rest; Sampling; Schizoaffective Disorders; Schizophrenia; Severities; Short-Term Memory; Signal Transduction; Site; Smooth Pursuit; Source; Specificity; Structure; Subgroup; Symptoms; System; Taxon; Testing; Training; Work; actigraphy; affective psychoses; base; clinically relevant; disease classification; effective therapy; experience; indexing; interest; neurophysiology; novel; paired stimuli; public health relevance; response; theories; therapy development; tool; treatment response; white matter

DESCRIPTION (provided by applicant): Psychotic symptoms are present in a significant subset of individuals with Bipolar Disorder (BD) and carry devastating personal and clinical implications. Most biomedical research on BD has ignored the variable presentation of psychosis possibly overlooking biologically significant heterogeneity in BD; such heterogeneity may cause inconsistencies in the literature by treating BD as a homogenous category 7,18. The expression of psychosis in some BD patients (BD-P) and absence in others (BD-NP) may indicate divergent disease processes of critical nosological and clinical relevance. PARDIP leverages a large sample of BD, a comprehensive battery, and sophisticated analytic tools to establish whether BD-P and BD-NP represent a difference in degree or a difference in kind. Long-term goals: This work will critically impact how BD is classified and studied, provide robust targets for effective future etiological studies, and clarify the utility of available biomarkers o major psychiatric disturbance. PARDIP represents a step toward mechanistically based classification of psychiatric disorders. Specific Aims: PARDIP will (i) identify the patterns of bo-cognitive disruptions which mark psychosis (BD-P`BD-NP) or mood instability in general (BD`healthy comparisons), (ii) explore how these biomarkers relate to one another and to other dimensions of psychopathology present in BD, and (iii) utilize latent class and cluster analyses of the multivariate dataset to verify taxonicity within BD with regard to psychosis and uncover latent psychiatric subgroups of interest for future genotyping and etiological research. Methods: The three-year PARDIP project will recruit 135 psychotic BD, 135 non-psychotic BD, and 135 psychiatrically healthy comparison subjects (all new recruits), administering a comprehensive battery focused on the psychosis and mania domains of psychopathology. We will obtain measures of neurophysiology, (smooth pursuit eye movements, antisaccades, auditory ERPs), cognition (cognitive battery, response inhibition, spatial working memory), neuroanatomy (structural magnetic resonance imaging [MRI]), emotional processing (ERPs to emotional pictures), intrinsic brain state (resting functional MRI connectivity), and circadian function (Actigraphy). We will compare biomarkers between BD-P, BD-NP, and H groups to determine which track with psychosis and which track with affective disturbance. We will identify common sources of variance among measures with joint-ICA and PCA approaches, and examine how biomarkers and biomarker composites relate to other aspects of clinical heterogeneity. Taxometric procedures (MAXCOV- HITMAX and its multivariate extension MAXEIG-HITMAX and k-means clustering) will be carried out with the multivariate dataset to empirically identify distinct subgroups of subjects. PARDIP will be conducted by 4 experienced research groups (across 3 collection sites) with a long history of close and productive collaboration.

描述（由申请人提供）：精神病症状存在于躁郁症（BD）的大部分子集中，并具有毁灭性的个人和临床意义。关于BD的大多数生物医学研究都忽略了精神病的可变表现，可能会忽视BD中生物学上显着的异质性。这种异质性可能通过将BD视为同质类别7,18，可能导致文献中的不一致。某些BD患者（BD-P）的精神病表达和其他人的缺失（BD-NP）可能表明临界病理学和临床相关性的疾病过程不同。 Pardip利用了大量的BD样本，全面的电池和复杂的分析工具来确定BD-P和BD-NP是否代表了学位或类型差异的差异。 长期目标：这项工作将严重影响BD分类和研究的方式，为有效的未来病因研究提供强大的目标，并阐明可用的生物标志物的实用性。 Pardip代表了基于机械的精神疾病分类的一步。 Specific Aims: PARDIP will (i) identify the patterns of bo-cognitive disruptions which mark psychosis (BD-P`BD-NP) or mood instability in general (BD`healthy comparisons), (ii) explore how these biomarkers relate to one another and to other dimensions of psychopathology present in BD, and (iii) utilize latent class and cluster analyses of the multivariate dataset to verify BD在精神病和揭露了未来基因分型和病因研究的潜在精神病学亚组。 方法：为期三年的Pardip项目将招募135个精神病性BD，135个非精神病学BD和135个精神健康的比较主题（所有新招聘人员），管理着针对精神病和精神病理学的躁狂症领域的全面电池。我们将获得神经生理学，（追踪眼动，反攻击，听觉ERP），认知（认知电池，抑制作用，空间工作记忆），神经解剖学（结构磁共振成像[MRI]），情绪处理（ERP到情感图片），固有的脑状态（固有的脑力）（RESIGNAINS MRI CONTICTIS）和RENCTICATION CONTICTION（RESIGNIC）的连接（RESIGE）和连接。我们将比较BD-P，BD-NP和H组之间的生物标志物，以确定哪种轨道患有精神病以及具有情感干扰的轨道。我们将通过联合-ICA和PCA方法确定措施之间的常见差异来源，并研究生物标志物和生物标志物复合材料如何与临床异质性的其他方面相关。分类程序（MaxCov-Hitmax及其多元扩展Maxeig-hitmax和K-均值聚类）将使用多元数据集进行，以凭经验识别出不同的受试者亚组。 Pardip将由4个经验丰富的研究小组（跨3个收集地点）进行，并具有悠久的亲密和富有成效的合作历史。