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: 9108447
• 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/9108447
• 关键词: Accounting; Address; Adult; Affect; Age; Aging; Anti-Inflammatory Agents; Anti-inflammatory; Behavior Therapy; Behavioral; Behavioral Mechanisms; Biological; Biological Response Modifier Therapy; 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; 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; mood symptom; 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）：随着人口老龄化，由于严重精神疾病（如双相情感障碍（BD））对认知和健康的影响，个人和社会的负担将增加。BD的过早和加速老化轨迹开始在许多健康和认知领域得到认可，但具体机制尚未确定，特别是认知老化过程。众所周知，炎症功能标志物（例如细胞因子水平）会影响认知，随年龄而变化，并预测心理健康个体的衰退。BD患者的细胞因子水平似乎也异常，但BD患者的情绪不稳定使得炎症和认知指标的短期和长期变化的测量具有挑战性。尽管如此，在这一人群中进行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调节或介导免疫认知相关性。我们建议使用创新的多队列爆发纵向设计（MBLD）来表征认知和炎症反应的轨迹，并确定：1）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）炎症标志物的基线测量和短期变异性水平，可能预测认知变化的长期轨迹，和3）长期的炎症、认知和情绪变量之间的关系（即，变化机制）。我们将评估144名患有临床相关情绪失调症状的成人（35-60岁），如双相I诊断所示，以及115名年龄相似的无精神疾病的非BD比较（NC）参与者。认知、细胞因子水平和情绪（沿着其他潜在影响变量） 将在两周内每周或每天使用密集的远程监测和家访（爆裂评估）进行测量。BD组将每年重复一次爆破评估（纵向评估），持续3年，NC组将每年重复一次爆破评估。该项目涉及NIMH战略目标#2：绘制精神疾病轨迹，以确定何时，何地以及如何干预。具体来说，使用一种创新的设计，使我们能够解释和测量情绪症状的变化的影响，我们可以发现炎症标记物（静态和动态），预测情绪不稳定个体的认知变化过程。通过了解炎症、认知和情绪之间复杂而动态的相互作用，可以设计药物和行为干预措施来减缓或逆转双相情感障碍功能下降的轨迹。