3/4-Psychosis & Affective Research Domains and Intermediate Phenotypes (PARDIP)

3/4-精神病

• 批准号: 8917630
• 负责人: GODFREY D PEARLSON
• 金额: $ 20.11万
• 依托单位: YALE UNIVERSITY
• 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/8917630
• 关键词: Affective; Anatomy; Anxiety; Auditory; Biological; Biological Markers; Biology; Biomedical Research; Bipolar Disorder; Bipolar I; 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; Health; 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; System; Taxon; Testing; Training; Work; actigraphy; affective psychoses; base; clinically relevant; disease classification; effective therapy; experience; indexing; interest; neurophysiology; novel; paired stimuli; psychotic symptoms; 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)：精神病症状存在于双相情感障碍(BD)的一个重要亚群中，并具有毁灭性的个人和临床影响。大多数关于BD的生物医学研究忽略了BD中精神疾病的不同表现形式，可能忽略了BD在生物学上的显著异质性；这种异质性可能会导致文献中的不一致，将BD视为同质类别7，18。一些BD患者的精神病表现(BD-P)和其他BD患者的缺失(BD-NP)可能表明具有关键病因学和临床相关性的不同疾病过程。Pardip利用大量的BD样本、全面的电池和复杂的分析工具来确定BD-P和BD-NP代表的是程度上的差异还是种类上的差异。长期目标：这项工作将对BD的分类和研究产生重要影响，为未来有效的病因学研究提供可靠的靶点，并阐明可用生物标记物在主要精神障碍中的作用。PARDIP代表着朝着基于机械的精神障碍分类迈出了一步。具体目标：PARDIP将(I)确定标志着精神病(BD-P`BD-NP)或一般情绪不稳定(BD‘健康比较)的BD-认知障碍的模式，(Ii)探索这些生物标记物彼此之间以及与BD中存在的精神病理学的其他方面的关系，以及(Iii)利用多变量数据集的潜伏类和聚类分析来验证BD内与精神病相关的分类，并发现潜在的精神病学亚群，用于未来的基因分型和病因学研究。方法：为期三年的PARDIP项目将招募135名精神病型BD、135名非精神病型BD和135名精神健康对照对象(均为新招募人员)，管理一套专注于精神病理学的精神病和躁狂领域的综合单元。我们将获得神经生理学(顺畅追逐眼球运动、防眼跳、听觉事件相关电位)、认知(认知电池、反应抑制、空间工作记忆)、神经解剖学(结构磁共振成像[MRI])、情绪处理(情绪图片的事件相关电位)、脑内在状态(静止功能磁共振连通性)和昼夜节律功能(活动描记)的测量结果。我们将比较BD-P、BD-NP和H组之间的生物标志物，以确定哪个轨道与精神病有关，哪个轨道与情感障碍有关。我们将使用联合ICA和主成分分析方法确定测量之间的共同差异来源，并检查生物标记物和生物标记物组合如何与临床异质性的其他方面相关。将对多变量数据集执行税收计量程序(MAXCOV-HITMAX及其多变量扩展MAXEIG-HITMAX和k-均值聚类)，以经验性地识别不同的受试者亚群。PARDIP将由4个经验丰富的研究小组(横跨3个采集点)进行，他们有着长期密切和富有成效的合作历史。