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: 8706965
• 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/8706965
• 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; 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; 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）：双向情感障碍 (BD) 患者中很大一部分人存在精神病症状，并具有毁灭性的个人和临床影响。大多数关于 BD 的生物医学研究都忽略了精神病的可变表现，可能忽视了 BD 的生物学显着异质性；通过将 BD 视为同质类别，这种异质性可能会导致文献中的不一致 7,18。一些 BD 患者表现出精神病（BD-P），而另一些患者则表现出精神病（BD-NP），这可能表明具有重要疾病分类学和临床相关性的不同疾病过程。 PARDIP 利用大量 BD 样本、全面的电池和复杂的分析工具来确定 BD-P 和 BD-NP 是否代表程度差异或种类差异。 长期目标：这项工作将严重影响双相情感障碍的分类和研究方式，为未来有效的病因学研究提供强有力的目标，并阐明现有生物标志物对主要精神障碍的效用。 PARDIP 代表了朝着基于机制的精神疾病分类迈出的一步。 具体目标：PARDIP 将 (i) 识别标志着精神病 (BD-P`BD-NP) 或一般情绪不稳定（BD`健康比较）的 bo 认知破坏模式，(ii) 探索这些生物标志物与一个生物标志物之间的关系BD 中存在的精神病理学的另一个维度和其他维度，以及 (iii) 利用多变量数据集的潜在类别和聚类分析来验证 BD 中关于精神病的分类性并揭示潜在的精神病学未来基因分型和病因学研究感兴趣的亚组。 方法：为期三年的 PARDIP 项目将招募 135 名精神病性 BD、135 名非精神病性 BD 和 135 名精神健康的对照受试者（均为新招募者），对精神病理学的精神病和躁狂领域进行全面管理。我们将获得神经生理学（平滑追踪眼球运动、抗眼跳、听觉 ERP）、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（情绪图像的 ERP）测量）、内在大脑状态（静息功能 MRI 连接）和昼夜节律功能（体动记录仪）。我们将比较 BD-P、BD-NP 和 H 组之间的生物标志物，以确定哪些轨迹患有精神病，哪些轨迹患有情感障碍。我们将通过联合 ICA 和 PCA 方法确定测量中常见的方差来源，并研究生物标志物和生物标志物复合物与临床异质性的其他方面的关系。将使用多元数据集执行分类程序（MAXCOV-HITMAX 及其多元扩展 MAXEIG-HITMAX 和 k 均值聚类），以凭经验识别不同的受试者亚组。 PARDIP 将由 4 个经验丰富的研究小组（横跨 3 个收集点）进行，这些研究小组有着长期密切和富有成效的合作历史。