Neuroprogression across the Psychosis Spectrum in the Early Course of Illness

疾病早期过程中精神病谱系的神经进展

• 批准号: 10335172
• 负责人: KATHRYN Eve LEWANDOWSKI
• 金额: $ 48.23万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335172
• 关键词: Aftercare; Amygdaloid structure; Area; Autopsy; Brain; Chronic; Clinical; Clinical Data; Cognition; Cognitive; Communities; Data; Data Collection; Development; Diagnostic; Dimensions; Disease; Disease Progression; Early Intervention; Functional Imaging; Functional Magnetic Resonance Imaging; Growth; Heterogeneity; Hippocampus (Brain); Human; Imaging Techniques; Impaired cognition; Impairment; Individual; Insula of Reil; Intervention; Knowledge; Longitudinal Studies; Longitudinal cohort; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methodology; Modality; Modeling; National Institute of Mental Health; Nature; Neurobiology; Neurocognition; Neurocognitive; Onset of illness; Outcome; Outcome Measure; Parietal; Patients; Positioning Attribute; Positron-Emission Tomography; Process; Psychoses; Recovery; Research; Research Personnel; Sampling; Subgroup; Symptoms; Testing; Thalamic structure; Time; TimeLine; Ventricular; base; career; clinical predictors; cognitive change; cohort; connectome; critical period; design; early psychosis; effective intervention; effective therapy; first episode psychosis; functional outcomes; gray matter; improved; improved functioning; individualized medicine; interest; longitudinal design; loss of function; multimodality; neurocognitive test; preservation; prevent; primary outcome; reward processing; targeted treatment; white matter

PROJECT SUMMARY/ABSTRACT This is an NIMH R01 proposal entitled, “Neuroprogression across the Psychosis Spectrum in the Early Course of Illness.” Neuroprogressive changes that occur through the early years of illness have been described using neurocognitive testing, PET, CT, fMRI, and post-mortem brain studies; however, these studies rely mainly on cross-sectional data, and longitudinal studies involving frequent measurements are rare, limiting our understanding of the actual timing and trajectories of these measures within this critical time period. The development and implementation of targeted and effective treatments is critically dependent on clear understanding of the timing and nature of disease progression in order to target processes amenable to intervention. Thus, there is an urgent need to carefully characterize neuroprogression in the early course of psychosis if we are to develop effective interventions to target areas of preserved functioning, potentially preventing further decline and chronic loss of functioning. This knowledge gap severely limits our ability to develop targeted treatments when they may be most effective, and to tailor treatment to patients' needs. The aim of the present proposal is the systematic, multimodal characterization of neuroprogression throughout the early course of illness in a cross-diagnostic sample of patients with psychosis using an accelerated longitudinal design. First, we will measure neurocognitive and neurobiological change over the first eight years of illness in order to characterize variability of timing and magnitude of neuroprogression across key measures. Second, we will assess the predictive utility of neuroprogressive trajectories on clinical and functional outcomes. We will also leverage the heterogeneity in baseline cognitive and brain measures to characterize patients by neuroprogressive profile and test whether baseline profiles offer improved prediction of clinical and functional course. The richness of these data will also position us to explore heterogeneity of neuroprogressive trajectories and their associations with clinical and functional outcomes. It has been argued that combining data from clinical, structural and functional imaging, and cognitive measures is superior to monomodal data in the prediction of course and outcome (6). Findings from this project will hasten identification of actionable treatment targets that are closely associated with clinical outcomes, and provide guidance for individualized treatment implementation during a critical period where early intervention strategies may be most effective. Notably, this proposal aims to build on the Human Connectome Project for Early Psychosis (U01MH109977, PI: Shenton) by utilizing the same high-quality methodology and adding longitudinal assessments to baseline data collection already underway, maximizing both the power of the present study and the utility of the HCP-EP data. The PI is an early stage investigator and K23 Awardee with a career focus on characterization of the nature and course of multidimensional symptom domains (e.g. cognition, reward processing), and targeted treatment approaches in psychosis.

项目总结/摘要 这是一个NIMH R 01提案，题为“早期精神病谱系的神经进展 病”。在疾病的早期发生的神经进行性变化已经用 神经认知测试，PET，CT，fMRI和死后大脑研究;然而，这些研究主要依赖于 涉及频繁测量的横截面数据和纵向研究很少，限制了我们的研究。 了解这些措施在这一关键时期内的实际时间和轨迹。的 开发和实施针对性和有效的治疗方法关键取决于明确的 了解疾病进展的时间和性质，以便针对适合的过程 干预因此，迫切需要仔细描述早期病程中的神经进展， 精神病如果我们要发展有效的干预措施，以目标保留功能的领域， 防止进一步衰退和慢性功能丧失。这种知识差距严重限制了我们的能力， 在可能最有效的时候开发有针对性的治疗方法，并根据患者的需要进行治疗。 本建议的目的是系统的，多模式的表征神经进展 在一个精神病患者的交叉诊断样本中， 加速纵向设计。首先，我们将测量神经认知和神经生物学的变化， 疾病的前8年，以表征神经进展的时间和幅度的变异性 关键措施。其次，我们将评估神经进展轨迹对临床的预测效用。 功能性成果。我们还将利用基线认知和大脑测量的异质性， 通过神经进展性特征描述患者，并测试基线特征是否提供改善的预测 临床和功能过程。这些数据的丰富性也将使我们能够探索 neuroprogressive轨迹及其与临床和功能结局的相关性。有人认为 结合临床、结构和功能成像以及认知测量的数据优于上级 单模态数据在病程和预后预测中的应用（6）。该项目的结果将加速 识别与临床结果密切相关的可行治疗目标，并提供 在早期干预策略的关键时期指导个体化治疗的实施 可能是最有效的。值得注意的是，这项提案旨在建立在人类连接组项目的基础上， 精神病（U 01 MH 109977，PI：Shenton），采用相同的高质量方法，并添加 对基线数据收集的纵向评估已经在进行中， 本研究和HCP-EP数据的实用性。PI是早期研究者和K23获奖者， 职业生涯的重点是表征的性质和过程的多维症状域（例如， 认知，奖励处理）和精神病的靶向治疗方法。