Dynamic Inflammatory and Mood Predictors of Cognitive Aging in Bipolar Disorder

双相情感障碍认知老化的动态炎症和情绪预测因子

• 批准号: 8934150
• 负责人: LISA T EYLER
• 金额: $ 56.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8934150
• 关键词: Accounting; Address; Adult; Affect; Age; Aging; Anti-Inflammatory Agents; Anti-inflammatory; Behavior Therapy; Behavioral; Behavioral Mechanisms; Biological; Bipolar Disorder; Bipolar I; Characteristics; Cognition; Cognitive; Cognitive aging; Complex; Development; Diagnosis; Emotional; Future; Goals; Health; Home visitation; House Call; Immune; Immune response; Immune system; Impaired cognition; Individual; Inflammation; Inflammatory; Inflammatory Response; Intervention; Investigation; Lead; Measurement; Measures; Mediating; Mental disorders; Methods; Monitor; Moods; National Institute of Mental Health; Participant; Patients; Play; Population; Process; Role; Sampling; Severities; Societies; Symptoms; Technology; Variant; age related; aged; burden of illness; clinically relevant; cognitive change; cognitive function; cognitive performance; cohort; comparison group; cytokine; design; follow-up; functional decline; immune function; inflammatory marker; innovation; longitudinal design; middle age; novel; phase change; physical conditioning; premature; severe mental illness

DESCRIPTION (provided by applicant): As the population ages, the burden on individuals and society due to the cognitive and health effects of serious mental illnesses, such as bipolar disorder (BD), will increase. Premature and accelerated aging trajectories in BD are beginning to be recognized in many health and cognitive domains, but specific mechanisms have not yet been identified, particularly for the course of cognitive aging. Markers of inflammatory function, such as cytokine levels, are known to affect cognition, change with age, and predict declines in mentally healthy individuals. Cytokine levels also appear to be abnormal in those with BD, but mood instability in BD makes measurement of short- and long-term changes in both inflammatory and cognitive measures challenging. Nonetheless, studies within this population afford a unique opportunity to better understand how variations in the degree of emotional and behavioral dysregulation may moderate or mediate immune-cognitive associations. We propose to use an innovative multi-cohort burst longitudinal design (MBLD) to characterize trajectories of cognitive and inflammatory response and identify: 1) relationships between cognition and inflammation in the short term while accounting for effects of mood variability, 2) baseline measures and levels of short-term variability in inflammatory markers that might predict long-term trajectories of cognitive change, and 3) relationships between inflammatory, cognitive, and mood variables in the long-term (i.e., mechanisms of change). We will assess 144 adults (35-60 years old) with clinically-relevant symptoms of mood dysregulation, as indicated by Bipolar I diagnosis, and 115 similarly aged non-BD comparison (NC) participants without mental illnesses. Cognition, cytokine levels, and mood (along with other potential contributing variables) will be measured weekly or daily over a two week period using intensive remote monitoring and home visits (burst assessment). Burst assessments will be repeated annually (longitudinal assessment) for three years in the BD group, and at one year in the NC group. This project addresses NIMH Strategic Objective # 2: charting mental illness trajectories to determine when, where, and how to intervene. Specifically, using an innovative design that allows us to account for, and measure the impact of, variability in mood symptoms, we can discover inflammatory markers (both static and dynamic) that predict the course of cognitive change among individuals with mood instability. By understanding the complex and dynamic interplay between inflammation, cognition, and mood, pharmacologic and behavioral interventions can be designed to slow or reverse the trajectory of declining function in bipolar disorder.

描述（由申请人提供）：随着人口的年龄，由于严重精神疾病的认知和健康影响（例如双相情感障碍（BD）），对个人和社会的负担将增加。在许多健康和认知领域中，BD中的过早和加速的衰老轨迹开始被认可，但是尚未确定特定的机制，尤其是在认知衰老的过程中。众所周知，炎症功能的标志物（例如细胞因子水平）会影响认知，随着年龄的变化并预测精神健康的个体下降。在BD患者中，细胞因子水平似乎也异常，但是BD中的情绪不稳定性使得衡量炎症和认知措施的短期和长期变化具有挑战性。尽管如此，该人群中的研究提供了一个独特的机会，可以更好地了解情绪和行为失调程度的变化如何中度或介导免疫认知关联。我们建议使用创新的多螺旋式纵向设计（MBLD）来表征认知和炎症反应的轨迹，并确定：1）在短期内认知与炎症之间的关系，同时考虑情绪变异性的影响，2）基础测量和基线测量和基线测量和基础测量。炎症标志物中短期变异的水平可能预测了认知变化的长期轨迹，以及3）长期（即变化机制）中炎症，认知和情绪变量之间的关系。如双极I诊断所表明的那样，我们将评估144名患有与临床相关的情绪失调症状的成年人（35-60岁），而没有精神疾病的患者也有115名相似的非BD比较（NC）参与者。认知，细胞因子水平和情绪（以及其他潜在贡献变量） 将使用密集的远程监控和家庭访问（爆发评估）在两周内每周或每天进行测量。 BD组和NC组一年，每年将每年重复三年的爆发评估（纵向评估）。该项目解决了NIMH战略目标＃2：制定精神疾病轨迹，以确定何时，何地和如何干预。具体而言，使用一种创新的设计，该设计使我们能够考虑和衡量情绪症状变异性的影响，我们可以发现炎症标记（静态和动态），这些标记（静态和动态）可以预测情绪不稳定的人的认知变化过程。通过了解炎症，认知和情绪之间的复杂而动态的相互作用，可以设计药理学和行为干预措施，以减慢或扭转双相情感障碍功能下降的轨迹。